Clinical Trial Updates

The Latest Updates (Posted September 1, 2010)...

Drug Reduces Incidence of Choroidal Neovascularization in Phase IIb

ReVision Therapeutics Inc. in early September announced that data from a Phase IIb trial show that fenretinide (RT-101) reduced the incidence of choroidal neovascularization (CNV, wet age-related macular degeneration) by about 50 percent in patients with geographic atrophy (GA), the most advanced form of dry age-related macular degeneration (AMD). The data, presented at the Annual Meeting of the American Society of Retinal Specialists, also showed a trend for reduced GA lesion growth rates in patients receiving fenretinide. These data suggest that fenretinide may have an effect on both GA lesion size as well as the conversion to the more sight-threatening wet form of AMD. Fenretinide is the first oral therapeutic to complete a Phase II trial in GA patients. The double-masked, placebo-controlled, multicenter study evaluated 246 patients with GA. Patients were randomized into three cohorts and received once-daily doses of 100 mg or 300 mg of fenretinide or placebo for 24 months. Retinal lesion size was measured by color fundus photography, fundus autofluorescence, and fluorescein angiography. Patients were also evaluated by contrast sensitivity, reading rate, visual acuity, optical coherence tomography, and the incidence of CNV. At the conclusion of the two-year study, 15 of 82 patients (18.3 percent) in the placebo arm progressed to CNV, while 15 of 164 patients (9.2 percent) receiving fenretinide at either dose developed CNV. While the results were statistically significant, this was the result of exploratory and ad hoc analyses. Source: PRNewswire 9/1/10

Success Stops Stroke Prevention Drug Trial

The data monitoring committee of the AVERROES study, seeing overwhelming evidence of the success of apixaban in the prevention of stroke in patients with atrial fibrillation who are unsuitable for the conventional treatment of warfarin, has recommended early termination of this study. The decision came after repeated review and careful consideration of all efficacy and safety data. The study leaders, principal investigator Dr. Stuart J. Connolly, chairman of the steering committee Dr. Salim Yusuf, and project officer Dr. John Eikelboom, have accepted this recommendation, as have the study sponsors, Bristol-Myers Squibb and Pfizer. Results of the study were presented by Connolly at the annual European Society of Cardiology Congress in Stockholm, Sweden, on August 31. The AVERROES study enrolled 5,600 patients with atrial fibrillation at risk for stroke who were unsuitable for therapy with a Vitamin K antagonist such as warfarin. These patients were randomized, double-blind, to receive either apixaban or the standard therapy (aspirin). The primary efficacy outcome of the AVERROES study was a composite of stroke or systemic embolism and the major safety outcome was major bleeding. The data monitoring committee observed a relative risk reduction for stroke and systemic embolism of more than 50 percent, which was highly statistically significant and which met the highly conservative monitoring boundaries of the AVERROES study. There was only a modest increase in major hemorrhage that was not statistically significant. Apixaban is a new type of anticoagulant known as a Factor Xa inhibitor, which is being jointly developed by Bristol-Myers Squibb and Pfizer. This agent blocks the coagulation system and can be used without the need for monitoring necessary in traditional treatments. It has been studied and shown promising results in patients with deep vein thrombosis, in patients with recent orthopedic surgery, and after acute coronary syndrome. It had not previously been studied in patients with atrial fibrillation. All patients in AVERROES who are still receiving study medication will be offered a long-term, open-label extension phase of the study in which they will receive apixaban, once the extension has been approved by regulatory bodies and local ethics committees. The AVERROES study was performed globally in more than 40 countries and coordinated by the Population Health Research Institute at McMaster University and at Hamilton Health Sciences. Source: EurekAlert! 8/31/10

Positive Phase IIa Data Seen for Oxygen Therapeutic Agent in Trauma Patients

Sangart, Inc., in late August announced positive results from its Phase IIa proof-of-concept study of MP4OX (oxygenated pegylated hemoglobin) in severely injured trauma patients with hemorrhagic shock causing lactic acidosis. The study demonstrated that MP4OX, when given in addition to standard of care, was effective at decreasing lactate levels in treated patients. During hemorrhagic shock, inadequate perfusion of critical organs can lead to insufficient oxygenation of tissues, which can be detected by an increase in lactate levels. MP4OX is a novel oxygen therapeutic agent that is designed to provide rapid oxygen delivery to ischemic tissues. Study data show a statistically significant greater immediate and sustained decrease of lactic acid in patients treated with MP4OX compared to patients in the control group. The study also found that a greater proportion of patients treated with MP4OX were able to attain normal lactate levels as early as four hours post-treatment. Furthermore, data demonstrated a strong trend toward outcomes benefits through multiple measures, including reducing the average total number of days patients spent in hospital. In patients treated with MP4OX, the median hospital stay was half that of the control group. Serious adverse events were of equal rates and similar in nature between the MP4OX-treated and control groups. The clinical trial was a multicenter, randomized, double-blind, controlled study that enrolled 51 patients who suffered trauma-induced severe hemorrhagic shock across 11 clinical sites in the United Kingdom, Germany, France, and South Africa. The primary objective of the study was to measure reduction in lactate levels after infusion of MP4OX. The company plans to further develop and clinically evaluate MP4OX and initiate Phase IIb clinical studies in trauma patients. Source: EurekAlert! 8/31/10

Clinical Studies Prove Natural Remedy for Constipation

According to Global Healing Center, results of newly published clinical studies scientifically prove that the company's Oxy-Powder®, an all-natural colon cleansing supplement, effectively relieves constipation in many patients. Of the 26 patients who participated in the 42-day trials, 25 were documented as having "Good" to "Excellent" results using the product to treat their constipation. Eleven of the 26 participants met the criteria for "Complete Remission," according to the researchers charged with conducting the formal scientific studies. The human trials closely monitored the effects of the popular dietary supplement on individuals who had suffered from ongoing constipation for a minimum of 12 weeks prior to joining the study. Routine stool examination carried out before and after the trials showed no abnormality in any of the patients. Source: PRNewswire 8/31/10

Pharmacodynamic Data Announced from Phase IIb of Factor Xa Inhibitor

Portola Pharmaceuticals, Inc. in late August announced additional pharmacodynamic data from a prespecified analysis of EXPLORE-Xa, a Phase IIb dose-finding study of betrixaban, an investigational oral direct Factor Xa inhibitor. The data come from the analysis of three separate pharmacodynamic markers for anticoagulation (anti-Factor Xa units, thrombin generation, and D-dimer) in plasma samples collected from 508 patients enrolled in the trial. The results showed a concentration-dependent relationship and provided further evidence for the anticoagulant activity of betrixaban across all three doses studied in the clinical trial. Previously presented data from the trial showed that a once-daily dose of oral betrixaban, given to patients with nonvalvular atrial fibrillation or atrial flutter and at least one risk factor for stroke, reduced the incidence of major and clinically relevant nonmajor bleeds compared to dose-adjusted warfarin. The additional pharmacodynamic analysis from the EXPLORE-Xa trial further demonstrated anticoagulant activity of betrixaban and provides information for dose selection for Phase III evaluation of betrixaban in stroke prevention. One hundred and twenty-seven patients were randomized to each of four treatment groups: betrixaban 40, 60, or 80 mg or open-label warfarin (INR 2-3), the current standard of care. The study was conducted in 35 centers in the U.S., Canada, and Germany with a minimum follow-up of three months and a maximum of 12 months. Source: Marketwire 8/29/10

Findings Released from Traumatic Brain Injury Study in the Emergency Department

BrainScope Company, Inc. in August announced the publication of clinical research findings from a study in patients presenting to the Emergency Department (ED) following a closed head injury. The study published in the peer-reviewed journal Brain Injury suggests BrainScope's technology, compared to computed tomography (CT), may provide clinically useful triage for CT in patients presenting to the ED. The purpose of the study was to determine the feasibility of BrainScope's technology to distinguish between patients who present with mild head injury symptoms, but result in either a positive head CT scan (CT+) (a head injury severe enough to warrant more extensive evaluation and treatment), a negative head CT scan (CT-), and ED control (normal) patients. The study, conducted in collaboration with Washington University's Barnes Jewish Hospital and New York University's Bellevue Hospital Center, involved written informed consent and enrolled 105 head injury patients (53 CT+ and 52 CT-) with complaints of altered mental status following a closed head injury and 50 ED controls patients. The majority of patients were enrolled within 24 hours of the suspected injury and involved a variety of mechanisms for injury, including assaults, falls, motor vehicle, pedestrian, and sport-related accidents. The BrainScope device was used to assess the degree of abnormality in brain function as measured by brain electrical activity. The findings of the independent study indicate that despite no significant differences between reported clinical symptoms in the CT+ and CT- groups, the BrainScope technology demonstrated high sensitivity (92.4 percent) and specificity (90 percent) in identifying the CT+ group, those patients who needed immediate imaging. Additional studies to replicate and further investigate the potential clinical utility of BrainScope's technology in the ED are currently under way. Source: PRNewswire 8/26/10

Firm Applies to FDA for First Chronic Spinal Cord Injury Stem Cell Trial

Neuralstem, Inc. announced that it has filed an Investigational New Drug (IND) application with the United States Food and Drug Administration (FDA) to begin a Phase I safety clinical trial for chronic spinal cord injury with its spinal cord stem cells. This multicenter Phase I safety trial will enroll a total of 16 long-term, or chronic, spinal cord injury patients, with an American Spinal Injury Association (ASIA) Grade A level of impairment, one-to-two years post-injury. ASIA A refers to a patient with no motor or sensory function in the relevant segments and is considered to be complete paralysis. The company is proposing to transplant patients with injuries in the thoracic (mid-back) regions first. Once the safety of the surgeries has been established, it plans to transplant patients whose injuries are in the cervical (upper spinal cord) region. Transplantation of Neuralstem's human spinal stem cells is meant to provide a neuron-rich substrate to the injured segments of a patient's spinal cord to promote further repair, regeneration, and reorganization. The goal is to harness this inherent plasticity and promote reorganization by combining stem cell transplantation with the modern concept of activity-guided rehabilitation. Neuralstem believes that, in chronic cases, the transplants may promote reorganization of segmental circuitry over the long-term. In the cervical region of the spinal cord, this could result in improved breathing capacity and recovery of sensori-motor functions of the upper limbs. Segmental reorganization induced by, and utilizing graft-derived neurons, may also result in improved locomotion. Neurons differentiated from Neuralstem's HSSC grafts in chronic thoracic injuries may serve as a bridge to connect the axons located above the site of injury to neurons of segments below the injury site. HSSC grafts may also encourage axons to regenerate through the graft to segments below the injury. Source: EurekAlert! 8/25/10

Clinical Trial Confirms Effectiveness of Simple Appetite Control Method

Has the long-sought magic potion in society's "battle with the bulge" finally arrived? An appetite-control agent that requires no prescription, has no common side effects, and costs almost nothing? Scientists in August reported results of a new clinical trial confirming that just two eight-ounce glasses of the stuff, taken before meals, enables people to shed pounds. The weight-loss elixir, they told the 240th National Meeting of the American Chemical Society, is ordinary water. "We are presenting results of the first randomized, controlled intervention trial demonstrating that increased water consumption is an effective weight loss strategy," said Virginia Tech's Brenda Davy, PhD, senior author on the study. "We found in earlier studies that middle aged and older people who drank two cups of water right before eating a meal ate between 75 and 90 fewer calories during that meal. In this recent study, we found that over the course of 12 weeks, dieters who drank water before meals, three times per day, lost about five pounds more than dieters who did not increase their water intake." The study included 48 adults aged 55 to 75 years, divided into two groups. One group drank two cups of water prior to their meals and the other did not. All of the subjects ate a low-calorie diet during the study. Over the course of 12 weeks, water drinkers lost about 15.5 pounds, while the nonwater drinkers lost about 11 pounds. The Institute for Public Health and Water Research funded the study. Source: EurekAlert! 8/23/10

Phase II Trial Considers Radioactive Microspheres for Colorectal Cancer Liver Metastases

Radioactive yttrium-90 labelled resin microspheres (SIR-Spheres; Sirtex Medical, Sydney, Australia) appear to be a safe and effective treatment for patients with colorectal cancer liver metastases who have failed available chemotherapy options, according to the final results of a prospective multicenter Phase II trial conducted by the Italian Society of Locoregional Therapies in Oncology and published in the British Journal of Cancer. The results of the 52-patient study revealed that the liver tumors completely disappeared in one patient, and 11 patients had a partial response involving at least a 30 percent reduction in tumor size, which met the predetermined criteria for significance. A further 12 patients had stable disease. The liver tumors shrank sufficiently in two patients to enable potentially curative surgery to be performed. The median overall survival was 12.6 months for all patients in the trial, with significantly longer survival in the 24 patients who responded to SIR-Spheres or who had stable disease compared to nonresponders (median 16 months versus eight months), and 40 percent of the responders remaining alive at two years compared to none of the nonresponders. Patients in the study had to have liver metastases from colorectal cancer that could not be removed by surgery and which had progressed despite modern chemotherapy regimens containing oxaliplatin and irinotecan. The presence of metastases outside the liver did not exclude the patients from treatment as long as these were limited in number, size, and in the same organ. All patients were heavily pretreated, having received at least three previous chemotherapy regimens. The study was conducted by a multidisciplinary team of interventional radiologists, nuclear medicine physicians, medical oncologists, surgeons, and other specialists at the Regina Elena National Cancer Institute in Rome, the University of Bologna, the University of Udine, and the Fondazione Pascale Cancer Institute in Naples. SIR-Spheres is the only Food and Drug Administration-approved microsphere therapy for colorectal cancer liver metastases. Source: PRNewswire 8/19/10

Development of Alzheimer's Treatment Halted Based on Preliminary Phase III Results

Eli Lilly and Co. will halt development of semagacestat, a gamma secretase inhibitor being studied as a potential treatment for Alzheimer's disease, because preliminary results from two ongoing long-term Phase III studies (IDENTITY and IDENTITY-2) showed it did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. The company's decision does not affect the ongoing clinical trials of solanezumab, Lilly's other compound in Phase III trials as a potential Alzheimer's treatment. While both drugs focus on amyloid-beta proteins, which are believed to play a critical role in Alzheimer's disease, they have different mechanisms of action. Lilly also has two other compounds in earlier stages of clinical development; those studies are not affected by the August announcement. In two pivotal Phase III trials, semagacestat was compared to placebo in more than 2,600 patients with mild-to-moderate Alzheimer's disease. Lilly has now reviewed data from a preplanned interim analysis of semagacestat studies. This interim analysis showed that, as expected, cognition and the ability to complete activities of daily living of placebo-treated patients worsened. However, by these same measures, patients treated with semagacestat worsened to a statistically significantly greater degree than those treated with placebo. In addition, data showed semagacestat is associated with an increased risk of skin cancer compared to those who received placebo. Lilly is instructing clinical trial investigators for all semagacestat studies to contact study participants as soon as possible and tell them to immediately stop taking the study drug they have received. Study participants or caregivers should call their study physician to schedule their next appointment. Lilly has appropriately informed regulatory agencies and is providing instructions to investigators outlining the process for finalizing the studies. Lilly's clinical team will continue to gather and evaluate data from these studies, and will publish the results for the benefit of future Alzheimer's research. Although dosing with semagacestat is being stopped, Lilly plans to continue collecting safety data, including cognitive scores, for at least six months through regularly scheduled follow-up visits with study physicians and modifications of the existing Phase III protocols. These additional follow-up visits will help to answer a number of important questions, including whether the differences between patients who received semagacestat and those who received placebo will continue after semagacestat has been discontinued. Other smaller short-term studies will be stopped and participants will receive appropriate follow-up. Source: PRNewswire 8/17/10

Earlier Updates...

Follow-Up Data of Heart Failure Device Trial to be Presented

Cardiac Dimensions has announced that the 12-month follow-up results from the TITAN™ trial of the company's Carillon® Mitral Contour System will be presented at the European Society of Cardiology 2010 Congress on August 29 in Stockholm. Professor Dr. Uta Hoppe of the University of Cologne, Germany, will present the data and review the safety and efficacy of the Carillon system, a novel therapy for treating heart failure patients suffering from functional mitral regurgitation (FMR), a disorder of the heart's mitral valve. The Carillon System is a nonsurgical, minimally invasive device designed to repair the mitral valve and reduce FMR. It combines a proprietary implantable device and a percutaneous delivery system. Source: PRNewswire 8/18/10 

Phase II Trial Initiated for Topical Therapy for Post Herpetic Neuralgia

Xenon Pharmaceuticals Inc. announced in August that it has initiated a Phase II clinical trial evaluating its novel topical XEN402 therapy for the treatment of post herpetic neuralgia (PHN). XEN402 has been developed by Xenon as a topical ointment formulation and recently concluded a 21-day cumulative dose safety tolerability Phase I study in normal human volunteers. The product was well tolerated and achieved good drug concentrations in the skin. Topical XEN402 is being developed by Xenon for painful neuropathic disorders such as PHN and targets the sodium channel sub-type Nav1.7. This target is highly expressed in sensory nerve endings and its expression has been shown to be up-regulated in chronic painful conditions such as PHN. The company expects to conclude the trial in the first quarter of 2011, with top-line data available in the second quarter. Source: PRNewswire 8/17/10 

Probiotic Shown Effective in Dietary Management of Children with Irritable Bowel Syndrome

New data show that VSL#3, a high-potency probiotic medical food, provides effective dietary management of children affected with irritable bowel syndrome (IBS). These data were published in the July issue of the Journal of Pediatric Gastroenterology and Nutrition. "There is evidence that some probiotics, such as VSL#3, have a beneficial role in the dietary management of children and teenagers suffering with IBS," said Stefano Guandalini, MD, professor and chief of the Section of Pediatric Gastroenterology, Hepatology, and Nutrition at the University of Chicago. "This has the potential to make a real difference for kids who suffer from pain, bloating, and discomfort of IBS." This investigation was a randomized, double-blind, placebo-controlled, crossover trial conducted in five pediatric tertiary care centers. A total of 59 children completed the study. Although placebo was beneficial in some of the parameters and in as many as half of the patients, VSL#3 was significantly superior to placebo in reaching the primary (relief of symptoms) and most secondary endpoints (abdominal pain/discomfort, abdominal bloating/gassiness, and family assessment of life disruption). Source: PRNewswire 8/16/10 

New Intra-Nasal Cooling System May Improve Survival When Initiated Soon After Cardiac Arrest

A new portable system that cools the brain via the nasal cavity may improve survival following cardiac arrest compared to standard care procedures, particularly when CPR and cooling are initiated early. Results from a recent study showed that the RhinoChill™ Intra-Nasal Cooling System enabled brain temperature to reach target several hours earlier than patients cooled in the emergency room. It is widely recognized that the sooner brain temperature can be reduced, the better the chances of minimizing long-term damage. The study, published online in the journal Circulation, is the first to evaluate cooling using this system in a randomized protocol conducted in the field and during the arrest. The Pre-Resuscitation Intra-Nasal Cooling Effectiveness (PRINCE) study involved 200 patients with witnessed cardiac arrest across 15 locations in Belgium, Germany, Italy, Czech Republic, and Sweden, where CPR had been initiated within 20 minutes of collapse. Patients were randomized to either intra-nasal cooling with RhinoChill along with standard advanced cardiac life support (ACLS) care or ACLS alone until they were either resuscitated or reached hospital, at which stage patients in both groups were cooled. Results showed that the target tympanic temperature of 34 degreesC, used as an approximation of brain temperature, was reached three hours earlier in the group receiving pre-hospital cooling with RhinoChill. Target core body temperature was also reached two hours earlier. Among patients surviving as far as hospital admission, 47 percent of patients who were cooled survived to discharge, compared to only 31 percent of those who had not been cooled. Survival rates in the 75 percent of patients who received CPR within 10 minutes of collapse were 59 percent and 29 percent, respectively. Thirty-seven percent of those cooled intranasally during the arrest survived neurologically intact, compared to only 21 percent of those not cooled in the field. Neurologically intact survival rates in patients who received CPR within 10 minutes of collapse were 46 percent and 18 percent, respectively. Source: PRNewswire 8/16/10 

Phase II Trial Focuses on EBV-Related Malignancies

HemaQuest Pharmaceuticals announced in August that it has initiated a Phase II clinical trial evaluating its proprietary HQK-1004 therapy for the treatment of lymphomas and related cancers associated with Epstein-Barr virus (EBV) infection. These EBV-related cancers have poor prognoses and short patient survival. Currently available cancer therapies are typically much less effective in patients with EBV-related lymphoid malignancies than in patients who have similar cancers not infected with the virus. In a Phase I clinical trial previously conducted by HemaQuest's scientific founders, 15 patients with relapsed or refractory EBV-related lymphomas were treated with a three-week infusion of HQK-1004 and the antiviral drug, Ganciclovir (GCV). Ten patients (67 percent response rate) demonstrated objective tumor responses, including several patients with complete tumor responses. This study provided support for previous laboratory studies demonstrating that HQK 1004 makes EBV-infected cancers susceptible to antiviral therapy. HQK-1004 enables the expression of the viral protein that is the target of antiviral drugs. Combining HQK-1004 with antiviral therapeutics now enables the killing of viral-infected tumor cells, while uninfected cells should not be affected. In the current trial, up to 40 patients with advanced EBV-related lymphoid malignancies will be treated with HQK-1004 and GCV at several clinical sites in the U.S. and abroad. The trial will test whether a shorter, five-day infusion of HQK-1004 can reproduce the promising results documented in the first clinical trial. With positive clinical results, the company plans additional studies to obtain Food and Drug Administration approval for this clinical indication. In addition, HemaQuest intends to test this therapeutic approach to treat other viral-related cancers. Source: PRNewswire 8/11/10 

Pivotal Phase III Trial for Triglyceride Treatment Completes Patient Enrollment and Randomization

Amarin Corp. in August announced that its MARINE trial, a Phase III clinical trial of AMR101, has completed patient enrollment and randomization into the treatment phase of this trial. The company indicated that top-line results from this trial are expected early in 2011, toward the early part of the range of guidance provided previously. The MARINE trial is a multicenter, placebo-controlled, randomized, double-blind, 12-week pivotal study to evaluate the efficacy and safety of 2 grams and 4 grams of AMR101 in patients with fasting triglyceride levels greater than or equal to 500 mg/dl. Patients in this trial are characterized as having very high triglyceride levels according to the National Cholesterol Education Program Adult Treatment Panel III treatment guidelines. The primary endpoint in the MARINE trial is the percentage change in triglyceride level from baseline after 12 weeks of treatment. Consistent with the protocol for this trial, the company expects that the 229 patients randomized in this study will be sufficient to achieve statistical significance. The MARINE study is the largest controlled therapeutic trial ever conducted in this population. Source: PRNewswire 8/10/10 

Positive Results Seen in Phase II Trial of Patch for Female Infertility

Vyteris, Inc. in August announced positive results from a Phase II clinical trial evaluating the safety and efficacy of a pulsatile delivery system for the treatment of female infertility, based on the company's smart patch technology. The trial enrolled 350 women between 18 and 38 years of age with ovulatory dysfunction. The trial assessed the safety and efficacy of three dosage strengths of pulsatile gonadotropin releasing hormone (GnRH) delivered from an iontophoretic patch compared to oral treatment with another leading infertility drug, and placebo. Based on the company's evaluation of the data, the trial met its primary endpoint by demonstrating a statistically significant difference in ovulation rates for the pulsatile GnRH versus placebo over the single, 21-day treatment cycle. Furthermore, among treatment-compliant patients who had at least one progesterone assessment on or after one week of dosing, the pulsatile GnRH achieved ovulation rates similar to the other leading infertility drug, which is considered a first-line treatment option for a majority of these patients. The most common adverse event in the trial was skin irritation at the site of administration. Source: Marketwire 8/10/10 

Company Submits Clinical Study Report to FDA for Phase II/III Acne Scarring Trial

Fibrocell Science, Inc. announced in August that it has submitted a clinical study report for its Phase II/III study of azficel-T for the treatment of moderate to severe acne scars to the U.S. Food and Drug Administration (FDA). The thorough analysis of study data contained in the report demonstrates that the study met all primary efficacy endpoints and was statistically significant. The product also is currently under review by the FDA for use in the treatment of nasolabial fold wrinkles. The placebo-controlled study investigating the efficacy and safety of azficel-T for the treatment of moderate to severe acne scars evaluated a total of 109 individuals at seven U.S. clinical sites. In the study, both the patient and evaluator assessments met the coprimary endpoints four months after the final study treatment, and were statistically significant. Source: PRNewswire 8/9/10 

Treatment for the Erythema of Rosacea Yields Positive Results

Vicept Therapeutics, Inc. announced positive results in August from a pharmacodynamic and pharmacokinetic clinical trial of the company's lead product V-101, a topical cream under investigation for the treatment of erythema in patients with rosacea. The double-blinded, placebo-controlled, crossover clinical trial of 22 patients with rosacea was designed to evaluate the bioavailability of V-101 and provide preliminary evidence of efficacy as measured by improvement in moderate to severe erythema, the bright redness of the skin associated with rosacea. V-101 had a side effect profile similar to placebo and V-101's active ingredient was not detectable in study participants' plasma, a strong indication of the product's overall tolerability and safety profile. Additionally, the study results were positive for all endpoints, demonstrating a clinically and statistically significant improvement in treating the erythema associated with rosacea. Source: PRNewswire 8/5/10 

New Drug Shown Safe, Effective in Treating Hereditary Angioedema

Clinical trials from two international research teams have shown that icatibant, a new drug that blocks the action of an inflammatory protein known as bradykinin, is safe and effective in treating acute attacks of hereditary angioedema (HAE), a potentially life-threatening condition. In their report in the August 5 New England Journal of Medicine, the authors note that – while the results of one trial did not reach statistical significance – the drug is safe and effective and further study will help clarify the patients and symptoms best treated with icatibant. HAE is caused by low levels or poor function of a protein called C1 esterase inhibitor. Patients with the condition suffer recurrent episodes of swelling caused by fluid leaking from blood vessels, and can experience potentially life-threatening airway blockage. Manufactured by the German pharmaceutical firm Jerini, Inc., icatibant has received approval in the European Union, where it is marketed under the brand name Firazyr. The study reports on two Phase III trials – one based in the U.S. and the other in Europe – conducted as part of Jerini's application to the U.S. Food and Drug Administration. Both studies were randomized, double-blind, prospective trials enrolling adults who had been diagnosed with HAE. The U.S.-based trial, called FAST-1, compared icatibant to a placebo for treatment of acute attacks; while the European trial, FAST-2, used trenaxminic acid, an oral medication available in Europe, as the comparison drug. Study participants – 56 for FAST-1 and 74 for FAST-2 – returned to their enrollment site for treatment within six hours of onset of a moderate to severe HAE attack. Response to the study medication was assessed by both patients themselves and by study investigators, who primarily evaluated the time required for relief of the most severe symptom and secondarily evaluated relief of all symptoms. A larger, worldwide Phase III trial of icatibant is currently in process. Source: EurekAlert! 8/4/10 

Patient Enrollment in Phase III Opioid Addiction Study is Ahead of Schedule

Titan Pharmaceuticals, Inc. in early August announced that patient enrollment is more than 60 percent complete in the confirmatory Phase III clinical study of Probuphine for the treatment of opioid addiction, and the study is expected to complete enrollment by early fourth quarter of this year, which is almost three months ahead of schedule. This placebo- and active-controlled study is being conducted at 21 sites in the United States, and will randomize approximately 250 patients to be treated for six months as follows: Probuphine (100 patients), Suboxone® (100 patients), and placebo (50 patients). Assuming full enrollment in the study on target, the results are expected to be available by late second quarter of 2011. This study is part of a registration-directed program intended to obtain marketing approval of Probuphine for the treatment of opioid addiction in the United States and Europe. Source: PRNewswire 8/3/10 

FDA Approves Initiation of Phase I for First-in-Class Drug

N30 Pharmaceuticals, LLC in early August announced the approval of its Investigational New Drug Application for N6022 by the U.S. Food and Drug Administration (FDA). N6022, a first-in-class inhibitor of s-nitrosoglutathione reductase (GSNOR), has the potential to be an important new treatment for acute exacerbations of asthma, chronic obstructive pulmonary disease (COPD), and inflammatory bowel disease (IBD). The company will now begin a first-in-human, Phase I, dose-escalation trial of N6022 in healthy subjects to assess the safety profile, tolerability, and pharmacokinetics of single intravenous doses of N6022. N6022 is a highly potent, selective, and reversible inhibitor of GSNOR. It is the lead product in N30 Pharma's portfolio of drugs, which are designed to treat asthma, COPD, and IBD. N6022 will initially be tested using intravenous administration. Data from this trial will provide important safety, pharmacokinetic, and biomarker information on which to base the design of subsequent trials of N6022, as well as the development of dosage forms suitable for chronic administration. Source: PRNewswire 8/2/10 

Menopausal Symptoms Treatment to Advance to Phase III Clinical Testing in Europe

Bionovo, Inc. announced in late July that it has received final guidance from the European Medicines Agency in order to advance Menerba, the company's lead drug candidate for menopausal symptoms, to Phase III clinical trials in Europe. The guidance defines the clinical and regulatory pathway to a European marketing authorization for Menerba. The product is being developed as an alternative to hormone therapy for the treatment of hot flashes. The company has also had a meeting with the U.S. Food and Drug Administration (FDA) on the development of Menerba in the U.S., and looks forward to providing more details when the minutes of the meeting are released. Menerba, an oral, botanically derived drug candidate, is an estrogen receptor beta selective drug. Clinical tests conducted thus far, following the specific guidance of the FDA, have indicated that Menerba is effective and safe. Source: PRNewswire 7/29/10 

Benefit Seen from Treatment for Restless Legs Syndrome

UCB in late July announced the results of a six-month, randomized, double-blind, placebo-controlled clinical study, published in the journal Movement Disorders, showing that Neupro® (rotigotine transdermal system, 2 and 3 mg/24 hours) provided sustained, clinically relevant improvements in symptoms of restless legs syndrome (RLS). The study also showed high rates of complete remission seen with rotigotine 2 mg or 3 mg/24 hours. The study represents the longest reported double-blind treatment period maintained in the U.S. for the evaluation of RLS treatments. One result was a high rate of complete remission from all RLS symptoms; approximately one of three previously moderately to severely ill patients was without any RLS symptoms after six months of treatment with either 2 or 3 mg of rotigotine. In the study, 505 patients were randomized to receive either placebo or rotigotine (0.5, 1, 2, 3 mg/24 hours) by transdermal administration. Source: PRNewswire 7/28/10 

First Patient Enrolled in Phase IIb for Pupil Dilation Product

Omeros Corp. in late July announced that it has enrolled the first patient in its Phase IIb clinical trial evaluating OMS302 in patients undergoing cataract surgery. OMS302, added to standard irrigation solution used during ophthalmologic surgery, is Omeros' proprietary PharmacoSurgery™ product in development to maintain mydriasis (pupil dilation) and reduce postoperative pain and inflammation following cataract and other lens replacement surgery. The study is using a full-factorial design to compare the individual agents in OMS302 to the proprietary drug product itself. Approximately 200 patients will be enrolled in the multicenter, randomized, double-blind, vehicle-controlled trial. Patients will be randomized into one of four parallel treatment groups of equal size. The first arm will receive OMS302, the second and third will receive only the mydriatic agent and the anti-inflammatory agent, respectively, and the fourth arm will receive a placebo of standard irrigation solution without drug. Positive results from this Phase 2b trial would enable Omeros potentially to initiate a Phase III clinical program of OMS302 in 2011. A prior Phase I/II clinical trial of 61 patients undergoing age-related cataract extraction with lens replacement showed that patients treated with OMS302 reported less postoperative pain and demonstrated statistically significant improvement in maintenance of mydriasis during the surgical procedure compared to patients treated with vehicle control. Source: PRNewswire 7/27/10 

Positive Top-Line Data Reported from Phase IIb Multiple Myeloma Study

Onyx Pharmaceuticals, Inc. in late July announced positive top-line results from the Phase IIb 003-A1 study of single-agent carfilzomib, a selective, next generation proteasome inhibitor, in patients with relapsed and refractory multiple myeloma. In an independent review of the data, carfilzomib achieved an overall response rate (partial response or greater) of 24 percent and a median duration of response of 7.4 months in patients who entered the study after receiving a median of five prior lines of therapy (corresponding to a median of 13 antimyeloma agents) and whose disease was refractory to their last therapeutic regimen. The clinical benefit rate (minimal response or greater) in the study population was 36 percent. Carfilzomib was well-tolerated and there were no new or unexpected toxicities observed. Full results of the trial will be presented at an upcoming scientific meeting. Based on these results, Onyx is continuing discussions with the U.S. Food and Drug Administration regarding next steps in filing a new drug application for carfilzomib, which the company expects to submit by year-end 2010 for potential accelerated approval in the U.S. The trial evaluated 266 heavily pretreated patients with relapsed and refractory multiple myeloma whose disease was refractory to their last treatment regimen and who had received at least two prior therapies, including bortezomib, either thalidomide or lenalidomide, an alkylating agent, glucocorticoids, and an anthracycline. Patients received carfilzomib at 20 mg/m2 for the first cycle followed by 27 mg/m2 thereafter for up to 12 cycles. Patients who completed the 12 cycles were eligible to enter an extension study. The trial was conducted in collaboration with the Multiple Myeloma Research Consortium (MMRC) and at additional sites in the U.S. and Canada. Source: PRNewswire 7/26/10 

Phase III Traumatic Brain Injury Trial Enrolls First Patient

BHR Pharma, LLC announced in July that the first patient has been enrolled in its SyNAPSe study, a global, Phase III, pivotal trial to evaluate the safety and effectiveness of its intravenous progesterone infusion product (BHR-100) as a neuroprotective agent for treating severe (Glasgow Coma Scale scores of 4-8) traumatic brain injury (TBI) patients. The study will randomize approximately 1,200 patients at more than 100 sites to receive a five-day (120-hour) continuous intravenous infusion of progesterone or placebo. The study protocol requires that treatment begin within eight hours of injury. Patients will be followed for six months post-injury. The first patient was enrolled at the University of Pittsburgh Medical Center in Pittsburgh, Pa. BHR was notified in June that the U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research had completed its special protocol review and the SyNAPSe trial design and planned analysis adequately address the objectives necessary to support a regulatory submission. Under the FDA Special Protocol Agreement, BHR will be able to seek marketing approval of BHR-100 without additional pivotal trials, provided the SyNAPSe study results meet specific statistical significance targets and other measures. Last December, BHR announced that its product had been granted orphan drug status by the FDA Office of Orphan Products Development for early intervention in the treatment of moderate-to-severe closed-head TBI. The FDA also notified BHR in March that its agent had received a Fast Track Development Program designation, which accelerates the approval of investigational new drugs undergoing clinical trials. Source: PRNewswire 7/23/10 

Phase IIa Clinical Study Initiated in Chronic Kidney Disease

Akebia Therapeutics, Inc. in July announced that it has initiated dosing in patients for a Phase IIa single-dose clinical trial of AKB-6548, an orally bioavailable hypoxia-inducible factor-prolyl hydroxylase in development for anemia. Akebia recently completed a Phase Ib study of AKB-6548 that demonstrated a dose-dependent increase in erythropoietin (EPO), reticulocytes (immature red blood cells), and hemoglobin with no significant adverse events. Patients with chronic kidney disease often suffer from anemia, and the current treatment approach involves injectable products to increase a patient's level of EPO. AKB-6548 is designed to naturally increase EPO. The new study is designed to evaluate the safety, tolerability, and pharmacokinetics of a single dose of AKB-6548 in stage 3 and 4 chronic kidney disease patients. In addition, the efficacy of AKB-6548 will be ascertained by measuring EPO and other biomarker responses, including VEGF, hepcidin, transferrin, and ferritin. The trial will involve up to 28 patients and will be conducted at two sites in the United States. The study is expected to be completed by January 2011. Source: Marketwire 7/22/10 

Phase I Study Complete for Novel and Patented Obesity Therapy

Compellis Pharmaceuticals, Inc. announced in July, with its collaborator Pennington Biomedical Research Institute at Louisiana State University, that they have successfully completed a human Phase I pilot clinical trial. Study subjects were given one of three doses of the drug (CP404) to test safety, tolerability, and impact on smell perception. CP404 is a calcium channel blocker and has been used in oral dosage form to treat high-blood pressure. The novel mechanism for the drug therapy is based on the inhibition of calcium channel activity in the olfactory pathways. Local blockade of the sense of smell is predicted to reduce individuals' interest in food intake and lead to therapeutic weight reduction. For this pilot study, subjects were blindly administered either the drug or an inert saline solution via nasal spray. Blood pressure was checked on a frequent basis. No significant adverse events were reported. Smell testing documented a clear trend for temporary reduction in smell perception that spontaneously reversed over time. Based on the encouraging results, Phase II studies are now being planned for the second half of 2010 and will incorporate a change in eating behavior as an endpoint. Source: Marketwire 7/22/10 

Chronic Pain Studies Suspended Following Adverse Event Reports

Pfizer Inc. in July announced, at the request of the U.S. Food and Drug Administration (FDA), the suspension of the chronic low back pain and painful diabetic peripheral neuropathy studies in the clinical program for the investigational compound tanezumab. Investigation of the compound continues in some areas of high unmet medical need, including cancer pain. The FDA's request follows further consideration of reports of adverse events in osteoarthritis patients taking tanezumab, and the agency's concerns regarding the potential for such events in other patient populations in which the compound is being studied. Pfizer announced the suspension of tanezumab studies in patients with osteoarthritis in a June 23 press release. For studies on clinical hold, recruitment of new patients and the dosing of existing patients are suspended. Pfizer will continue to work with the FDA to reach a common understanding about the appropriate scope of continued clinical investigation of tanezumab. Source: PRNewswire 7/19/10 

Microbicide Trial Lifts Hope for Women's HIV Prevention

Results of a Phase IIb clinical trial of an antiretroviral-based microbicide candidate were announced at the International AIDS Conference in Vienna, Austria, in July. The CAPRISA 004 trial, which tested the safety and effectiveness of 1 percent tenofovir gel among nearly 900 women at two sites in South Africa, found that using the gel before and after sex provided moderate protection against sexually transmitted HIV. Tenofovir is an antiretroviral (ARV) drug that is used as an oral treatment for HIV in many countries and is licensed for use as HIV treatment in South Africa. CAPRISA 004 is the first trial to evaluate an ARV-based candidate microbicide gel for the prevention of sexually transmitted HIV infection among women. The trial commenced enrollment in May 2007 and completed follow-up in December 2009. The trial was conducted at two CAPRISA (Centre for the AIDS Programme of Research in South Africa) clinical research sites in the KwaZulu-Natal Province of South Africa: in an urban area of eThekwini (Durban) and a rural area of Vulindlela (Pietermaritzburg). Women in the trial were HIV-negative, sexually active, and at high risk of becoming infected with HIV. They were asked to vaginally insert a first dose of tenofovir gel no more than 12 hours before having sex, and to insert a second dose no more than 12 hours after having sex. No more than two doses of gel were used in a 24-hour period, even if the women had sex more than once. The trial was not designed to provide sufficient evidence to licence a new drug (which would generally require a definitive Phase III trial). The trial measured whether tenofovir gel reduced the risk of HIV infection among women provided with the tenofovir gel compared to women provided with a placebo gel. All participants received regular HIV risk-reduction counseling, condoms, and treatment of symptomatic sexually transmitted infections, if required. The trial also measured whether tenofovir gel was safe to use regularly over a longer period of time than had previously been assessed in clinical safety studies. Women in the trial typically used the gel for 12 to 18 months. The trial systematically collected information on all health complications, genital events, and systemic toxicity (if the drug reached the blood stream). The CAPRISA 004 trial also assessed if women who sero-converted during the trial developed resistance to tenofovir, and the effect that using tenofovir gel for HIV prevention had on the HIV viral load after seroconversion. The trial was conducted by a consortium that included CAPRISA at the University of KwaZulu-Natal in Durban; FHI in North Carolina; and CONRAD in Virginia. It was funded by the United States Agency for International Development and TIA, a biotechnology agency of the South African government's Department of Science and Technology. In addition, Gilead Sciences provided tenofovir for the manufacture of the gel used in the study. Source: PRNewswire 7/19/10 

Largest Study on Insulin Therapy Completes Recruitment with 60,000 Patients

In July, Novo Nordisk announced the landmark recruitment of the 60,000th patient in the A1chieve® study--an observational study designed to investigate the effects of modern insulins in the management of type 2 diabetes. Spanning 28 countries across four continents and involving more than 3,300 physicians, A1chieve is set to be the world's largest observational study in insulin therapy. Approximately 70 percent of the world's 285 million people with diabetes are living in these 28 emerging countries where there is a rising need and interest to look at differences in physician decisions in the management of diabetes. In order to mimic the natural secretion of insulin in the body, commercially available insulin preparations are used in different ways (regimens) based on an individual's need and prevailing local practices. However, it is important to evaluate these different regimens in a real-life setting. Once completed, A1chieve will provide locally relevant information on the effective use of modern insulins across different regimens. This information could be further useful to inform and improve the local guidelines on the management of type 2 diabetes. Source: PRNewswire 7/19/10 

Study Considers Efficacy and Safety of Moisturizing Lotion

The June 2010 issue of Journal of Drugs in Dermatology features a study on the long-term efficacy and tolerability of the active ingredient in PyratineXR™ moisturizing lotion. The results of the 48-week clinical study demonstrate that the product's cytokinin-based skincare technology is effective and well-tolerated for individuals suffering from inflammatory skin conditions such as acne, rosacea, sunburn, and razor burn. The rosacea-specific study was performed at the University of California, Irvine. In the open-label study, a moisturizing lotion containing furfuryl tetrahydropyranyladenine as PRK-124 (0.125 percent) was applied twice daily by 18 subjects with mild-to-moderate rosacea. Clinical improvements were assessed by the treating physicians. Skin barrier function was measured by transepidermal water loss after treatment. Tolerability and cosmetic outcome were evaluated by subjects. Subjects experienced a mean 44 percent reduction in erythema severity and a mean 89 percent reduction in inflammatory lesion count at week 48. Reductions were significant in both erythema and lesions at weeks 24, 36, and 48. Statistically significant improvements in telangiectasia (spider veins), transepidermal water loss, and dryness were noted. Overall clinical improvement was observed in 81 percent of subjects and the investigator's global assessment steadily improved throughout the study. Treatments were well tolerated and esthetically pleasing. Treatment-induced skin irritation was not observed. The published study concludes that PyratineXR is efficacious, does not irritate skin, and is well tolerated for continuous long-term treatment. Source: PRNewswire 7/15/10 

Two-Year Trial Shows Significant Weight Loss and Improved Maintenance

Arena Pharmaceuticals, Inc. and Eisai Inc. in July announced that results from the two-year BLOOM (Behavioral modification and Lorcaserin for Overweight and Obesity Management) trial were published in the July 15 issue of the New England Journal of Medicine. The data presented in the article show that lorcaserin, used in conjunction with behavioral modification, caused significantly greater weight loss and improved maintenance of weight loss compared to placebo. Lorcaserin also improved values for biomarkers that may be predictive of future cardiovascular events, including lipid levels, insulin resistance, levels of inflammatory markers, and blood pressure. At the end of Year 1 of the BLOOM trial, using Intent-to-Treat with Last Observation Carried Forward analysis, the proportion of patients achieving at least 5 percent body weight loss in the lorcaserin group (47.5 percent) was more than twice that achieved by the placebo group (20.3 percent). Nearly three times as many patients achieved at least 10 percent weight loss in the lorcaserin group (22.6 percent) than in the placebo group (7.7 percent). Lorcaserin patients who completed the first year of the trial according to the protocol lost an average of 8.2 percent of their baseline weight, or approximately 18 pounds, at the end of Year 1 as compared to approximately 7 pounds in the placebo group. In Year 2, patients who continued to take lorcaserin were significantly better able to maintain their Year 1 weight loss than those who were switched to placebo. In Year 1, lorcaserin caused significant decreases in waist circumference, body mass index, glycemic parameters, high-sensitivity C-reactive protein, and fibrinogen levels compared to placebo. Total cholesterol, LDL cholesterol, and triglyceride levels at Year 1 were significantly lower in the lorcaserin group than in the placebo group. Lorcaserin did not increase heart rate or blood pressure; rather, heart rate, systolic blood pressure, and diastolic blood pressure decreased slightly but significantly with lorcaserin treatment compared to placebo. Quality of life, measured by the Impact of Weight on Quality of Life-Lite questionnaire, improved in both treatment groups, with a greater improvement in the lorcaserin group than in the placebo group. At the end of Year 1, 55.4 percent of patients in the lorcaserin group and 45.1 percent of patients in the placebo group remained enrolled in the study, and 7.1 percent and 6.7 percent of patients, respectively, discontinued the study due to an adverse event. BLOOM, the first of three lorcaserin Phase III trials, is a double-blind, randomized, placebo-controlled trial involving 3,182 patients in 98 sites in the United States. Source: PRNewswire 7/14/10

SPA Submitted for Phase III of Diabetic Foot Infection Trial

Innocoll, Inc. announced in July that its wholly owned subsidiary, Innocoll Technologies Ltd., has submitted a Special Protocol Assessment (SPA) to the Food and Drug Administration (FDA) for a proposed Phase III clinical trial to support the U.S. approval of Cogenzia™, a topical antibiotic therapy for the adjuvant treatment of infected diabetic foot ulcers. The protocol was developed following an end of Phase II meeting with FDA where the results of Innocoll's Phase II clinical studies were presented and discussed. In the planned Phase III randomized, placebo-controlled, double-blind clinical trial, patients with a moderate or severe diabetic foot infection will be treated with Cogenzia on a daily basis as an adjunct to standard-of-care, which includes systemic antibiotic therapy administered by the oral or intravenous route. Patients will be treated for a maximum of 28 days and the primary endpoint will be the percentage of patients who are clinically cured of infection 10 days after discontinuation of all antibiotic therapy. In the Phase II trial, all Cogenzia-treated patients who completed the study achieved clinical cure, which was statistically significantly superior to 70 percent of patients in the control group. Patients in the Cogenzia group also had a significantly higher rate of baseline pathogen eradication and a reduced time to pathogen eradication. Source: PRNewswire 7/13/10 

Ibuprofen Injection Shown to Significantly Reduce Fever in Malaria Patients

Cumberland Pharmaceuticals Inc. in July announced that data supporting the efficacy of Caldolor® in treating fever associated with falciparum malaria was published in the July edition of the peer-reviewed American Journal of Tropical Medicine and Hygiene. The study, which is the first to document an antipyretic effect of an injectable nonsteroidal anti-inflammatory drug on fever caused by malaria, demonstrated that patients who received intravenous ibuprofen experienced a greater reduction in their temperatures than those who received placebo. Falciparum malaria is the most serious type of malaria and can be fatal within a few hours of the first symptoms. Currently, few options exist to treat fever in hospitalized patients who are unable to swallow or retain oral antipyretic therapy. The double-blind, placebo-controlled malaria trial evaluated 60 hospitalized adults with acute uncomplicated falciparum malaria who were treated with artemisinin combination therapy. Thirty patients received 400 mg of intravenous ibuprofen and 30 received placebo every six hours for 72 hours. Patients who received IV ibuprofen experienced a greater reduction in fever than those who received placebo during the first 24 hours, and on through 72 hours, following initial administration of study drug. The times for the mean temperature to fall below 37.0 degrees C were three hours for IV ibuprofen and 20 hours for placebo. Patients who received IV ibuprofen experienced a delay in parasite clearance, but this did not appear to be clinically important. Adverse events, none considered severe, occurred equally in both the ibuprofen and placebo groups. Source: PRNewswire 7/12/10 

Phase III Meeting with FDA to Follow Positive Results of Bone Marrow Regeneration Trial

Australian regenerative medicine company Mesoblast Limited in July announced that, based on positive results from its bone marrow transplant clinical trial conducted at the University of Texas MD Anderson Cancer Center, a formal meeting has been scheduled with the United States Food and Drug Administration (FDA) to discuss a proposed Phase III clinical trial program. For this program, the patented allogeneic Mesenchymal Precursor Cells (MPCs) will be used under an FDA Orphan Drug Designation to expand haematopoietic stem and progenitor cell numbers in patients with haematologic malignancies. Mesoblast's objective is to develop a therapy that results in effective bone marrow reconstitution without the potentially life-threatening complication of graft-versus-host disease, which occurs in as many as 60 percent of patients who receive bone marrow transplants from unrelated adult donors. In the first 25 patients transplanted with MPC-expanded haematopoietic progenitors from cord blood, 80 percent successfully achieved the key composite endpoint at 100 days of survival with sustained engraftment of both neutrophils and platelets. This is significantly higher than the rate of 38 percent for this composite endpoint achieved after transplantation with nonexpanded cord blood in the United States registry of 300 patients collected by the Center for International Blood and Marrow Transplant Research. To date, only four patients (16 percent) receiving expanded cord blood have developed severe graft-versus-host disease. Source: PRNewswire 7/11/10 

First Patient Enrollment in Defibrillator Trial

Boston Scientific Corp. in July announced enrollment of the first patient in its MultiSENSE clinical trial. The trial is designed to evaluate multiple physiologic sensors in the company's COGNIS™ cardiac resynchronization therapy defibrillators (CRT-Ds). Boston Scientific plans to use the trial data to help develop a clinical alert that identifies the early onset of worsening heart failure. The first patient was enrolled by Paul Coffeen, MD, of Austin Heart in Austin, Texas, where Jeffrey Whitehill, MD, medical chair of the Electrophysiology Department, is the site's principal investigator. When combined with the company's LATITUDE® Patient Management System, CRT-D sensors would be able to monitor a patient outside of a clinical setting and permit the LATITUDE system to deliver early notification to the physician when the patient's heart failure worsens. "Heart failure is a complex disease and physicians use a number of diagnostics to assess a patient's condition and disease progression," said John Boehmer, MD, medical director of the Heart Failure Program and professor of medicine at Penn State Hershey Medical Center, and principal investigator of the MultiSENSE trial. "A multisensor design in an implantable device, with the predictive power of multiple data points, would enable physicians to take clinical action sooner to avoid hospitalization due to heart failure." Source: PRNewswire 7/8/10 

Dosing Initiated in Phase I Clinical Trial Targeting Protein Abnormality

Tekmira Pharmaceuticals Corp. announced in July that one of the company's partners, Alnylam Pharmaceuticals, Inc., has initiated dosing in a Phase I human clinical trial of its product candidate ALN-TTR01. The study is designed to evaluate the safety and tolerability of ALN-TTR01 in patients with transthyretin (TTR)-mediated amyloidosis (ATTR), a disease that results in damage to the peripheral nerves and heart. The trial is also designed to provide preliminary data on human proof of concept based on measurements of TTR serum levels. ALN-TTR01 is a systemic RNAi therapeutic that uses Tekmira's leading lipid nanoparticle delivery technology, SNALP (stable nucleic acid-lipid particles). ATTR is caused by mutations in the TTR gene, which is expressed predominantly in the liver, and results in the accumulation of pathogenic deposits of amyloid proteins in multiple tissues, including the peripheral nervous system, heart, and the gastrointestinal tract. The trial will be conducted in Portugal, Sweden, and the U.K., and is a randomized, blinded, placebo-controlled, dose-escalation study designed to enroll approximately 28 ATTR patients. The primary objective is to evaluate the safety and tolerability of a single dose of intravenous ALN-TTR01 and secondary objectives include characterization of plasma and urine pharmacokinetics of ALN-TTR01 and assessment of pharmacodynamic activity based on measurements of circulating TTR serum levels. In its severest form, ATTR represents a tremendous unmet medical need with significant morbidity and mortality as an orphan disease; combined, FAP (familial amyloidotic polyneuropathy) and FAC (familial amyloidotic cardiomyopathy) affect approximately 50,000 people worldwide. ATTR patients with FAP have a mean life expectancy of five to 15 years from symptom onset and the only treatment option is liver transplantation; as a result there is a significant need for novel therapeutics to treat patients who have a mutation in the TTR gene. Source: Marketwire 7/7/10 

First Human Trial Initiated in Universal Flu Vaccine Program

Dynavax Technologies Corp. announced in July the first human clinical trial in its Universal Flu vaccine program. The Phase I trial, which began vaccinating subjects in late June, will assess the safety and immunogenicity of N8295, the novel component of Dynavax's Universal Flu vaccine candidate. Approximately 40 subjects, divided into three dose groups, will receive two immunizations of N8295, one month apart. N8295 is a fusion protein comprised of NP and M2e, two highly conserved influenza antigens covalently linked to Dynavax's proprietary second-generation TLR9 agonist. Dynavax expects to report data by year-end 2010. Novartis Vaccines and Diagnostics, Inc. is committed to supply influenza vaccine for Dynavax's clinical trials under a worldwide supply and option agreement signed in 2008. Novartis has an option to negotiate a joint development and commercialization agreement for Dynavax's Universal Flu vaccine and is obligated to provide commercial supplies of its vaccine once clinical proof-of-concept has been established. A clinical study to demonstrate proof-of-concept data is planned for 2011. Dynavax's Universal Flu Vaccine is designed to offer protection against divergent influenza strains as well as to increase the efficacy of a standard trivalent inactivated influenza vaccine. Preclinical data have confirmed the expected immunogenicity and mechanistic effects of the vaccine candidate's novel components. The production of cytotoxic T-cells by NP and cytotoxic antibodies by M2e have been demonstrated in preclinical studies, as has an increase in neutralizing antibodies provided by a coadministered inactivated influenza vaccine. A GLP toxicity study demonstrated that this Universal Flu vaccine candidate is well-tolerated. Source: Marketwire 7/7/10 

Enrollment Completed for Phase III Cushing's Syndrome Study

Corcept Therapeutics Inc. in July announced that it has completed enrollment of all 50 patients in its Phase III trial of Corlux® for the treatment of Cushing's syndrome and the study is now closed. The company said that dosing has begun in all patients in the open-label trial focused on endogenous Cushing's Syndrome, which is being conducted at 20 medical facilities throughout the United States in support of a planned New Drug Application (NDA) to the Food and Drug Administration. In the study, each patient's dose is titrated to clinical benefit by their study investigator, and the primary endpoints (either an improvement in glucose tolerance or blood pressure) are measured at the end of 24 weeks. The company expects to announce the top-line results of this study by the end of 2010 and to submit an NDA to the FDA in the first quarter of 2011. Endogenous Cushing's syndrome is caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol, due to either cortisol or adrenocorticotropic hormone production by tumors. Cushing's syndrome is an orphan indication that most commonly affects adults aged 20 to 50. An estimated 20,000 patients in the United States have Cushing's syndrome, the symptoms of which vary, but most people have one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue, and weak muscles. Irritability, anxiety, cognitive disturbances, and depression are also common. Cushing's syndrome can affect every organ system in the body and can be lethal if not treated effectively. Corlux, also known as mifepristone, directly blocks the cortisol (GR-II) receptor and the progesterone receptor. Source: Marketwire 7/1/10 

New Nonsurgical Treatment for Uterine Fibroids Can Improve Quality of Life

A new, effective, nonsurgical treatment for uterine fibroids can help women with this condition maintain their fertility, an American scientist told the 26th annual meeting of the European Society of Human Reproduction and Embryology in Rome in late June. Dr. Alicia Armstrong, chief of gynecologic services for the National Institutes of Health (NIH) Program in Reproductive and Adult Endocrinology, said that the outcome of two Phase II clinical trials of ulipristal acetate (UPA) had significant implications for both infertility and general gynaecology patients. UPA belongs to a relatively new class of drug, the selective progesterone receptor modulators (SPRMs). It is currently used for emergency contraception, and acts by blocking the progesterone receptor and hence ovulation (release of the egg). Recent research has shown that progesterone also plays a role in the development of uterine fibroids. "Both the fibroids and the surgical interventions commonly used to treat them can cause significant fertility problems," said Dr. Armstrong, "and we wanted to see whether fibroids could shrink and surgery could be avoided by using an SPRM." Results from two randomized, placebo-controlled, double-blinded studies performed at NIH were pooled and analyzed. In the trials, women aged from 25-50 years with symptomatic uterine fibroids were randomized to receive UPA or placebo once a day for three menstrual cycles. The researchers found that, out of the 57 patients who it was possible to evaluate for efficacy, 18 received placebo, 20 received 10 mg of UPA per day, and 19 received 20 mg per day. Those taking UPA had reduced total fibroid volume, with those taking the higher dose doing better. The patients on placebo did significantly less well. UPA also reduced bleeding compared to placebo and during the third month of treatment 16 (80 percent) of patients taking 10 mg daily and 18 (95 percent) on a daily dose of 20 mg experienced no menstrual bleeding. At the end of the treatment, patients on the active treatment scored higher in assessment of their quality of life, the severity of their symptoms, their energy levels and mood, and their overall concern about the effects of fibroids. "The results of these trials are convincing and lead us to conclude that UPA is an effective noninvasive treatment for fibroids that can help maintain fertility in women whose only option up to now was to have surgery," said Dr. Lynnette Nieman, principal investigator on the NIH trials. "We hope that the results from these trials, along with those from the Phase III trials currently being conducted by the Swiss company PregLem SA, will allow us to offer this treatment to women who do not want surgery or are unable to have it for medical reasons." Source: EurekAlert! 6/30/10 

Australian Company Reports Accelerated Recruitment into Rheumatoid Arthritis Trial

CBio Limited in late June announced the achievement of a recruitment milestone in its clinical trial of XToll, the potential new-generation drug therapy that could provide safer and more effective treatment of autoimmune diseases such as rheumatoid arthritis. CBio Managing Director Jason Yeates said that the company was very pleased with recruitment levels achieved by the new clinical trial sites in Central and Eastern Europe, as well as the continued support of the trial by sites in the company's home country of Australia. "One hundred fourteen of the targeted 150 patients have now been recruited into the clinical trial. This increased rate of recruitment means that full recruitment remains on track to complete by the end of September 2010..." Yeates said. "We continue to work towards completing this trial by the end of March next year. ...Given that the same research path might lead to alternative treatments for diseases such as lupus, the company is now investigating what resources would be needed to start an additional program in this area. ...However, we will not divert energy from the core rheumatoid arthritis program which is now highly advanced." CBio's preclinical research into therapeutic uses of XToll in diseases other than rheumatoid arthritis has been submitted to a number of global therapeutic conferences being held in late 2010. Source: PRNewswire 6/30/10 

Acromegaly Treatment Receives Orphan Drug Designation

Chiasma, Inc. in late June announced that the U.S. Food and Drug Administration has granted orphan drug designation for the company's investigational new drug, Octreolin, an oral form of octreotide acetate that uses the company's proprietary Transient Permeability Enhancer technology for the oral treatment of acromegaly, a hormonal disorder that results from an excess of growth hormone. If a New Drug Application (NDA) is approved, Octreolin should qualify for seven years of market exclusivity, potential tax credits, and a waiver of the prescription drug user fee for the marketing application. Chiasma has successfully completed a Phase I clinical study evaluating the safety and pharmacokinetics of Octreolin, which demonstrated a profile similar to that of subcutaneously injected octreotide acetate. The company intends to initiate a Phase III trial by the end of the year for Octreolin in acromegaly. Chiasma will submit an application for Orphan Medicinal Product Designation to the European Medicines Agency shortly, and intends to submit an NDA using the 505(b)(2) regulatory pathway in the United States and its equivalent, the Hybrid Application, in Europe. Octreolin would provide patients with the benefit of an oral alternative to the currently approved subcutaneous and intramuscular injections. In addition, the company is developing Octreolin as a potential treatment for patients with portal hypertension; a clinical trial to evaluate this new indication is expected to start in December of 2010. There are currently no drugs approved for portal hypertension in the U.S., and the company plans to request orphan drug designations for Octreolin for this indication in the U.S. and in Europe. Source: PRNewswire 6/28/10 

Results from Study of Vascular Calcification in Dialysis Patients Presented in Late-Breaking Session

Results from the ADVANCE study presented in a late-breaking clinical trial session at the ERA-EDTA 2010 Congress provide new insights into the management of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients. ADVANCE (A randomizeD VAscular calcificatioN study to evaluate the effects of CinacalcEt) is a randomized, controlled, open-label study to evaluate the effects of treatment with Amgen's Mimpara® (cinacalcet) plus low-dose vitamin D, compared to flexible doses of vitamin D alone, on the progression of vascular and valvular calcification in dialysis patients with SHPT. A trend was observed toward slower progression of vascular calcification at all sites evaluated among patients randomized to the cinacalcet arm, although the primary endpoint did not reach statistical significance. The primary endpoint for the study was percentage change in the Agatston CAC score from baseline to week 52. Agatston CAC scores [median, (Q1, Q3)] increased by 24 percent (-1 percent, 63 percent) from baseline in the cinacalcet group and by 31 percent (8 percent, 81 percent) in the flexible vitamin D group. Additional analyses were also performed using volumetric scoring of CAC, an alternative method for measuring CAC, and showed cinacalcet plus low-dose vitamin D significantly slowed the progression of calcification compared to flexible doses of vitamin D alone. Volume CAC scores increased by 22 percent (2 percent, 52 percent) from baseline in the cinacalcet group and by 30 percent (10 percent, 78 percent) in the flexible vitamin D group. ADVANCE also showed that cinacalcet plus low-dose vitamin D, compared to flexible doses of vitamin D alone, provided better biochemical control of SHPT as judged by the blood levels of parathyroid hormone, calcium, and phosphorus from baseline to the end of the study as demonstrated in previous studies. ADVANCE studied 360 patients with SHPT and detectable CAC. SHPT is a metabolic disorder that develops in chronic kidney disease patients on dialysis and results in increased secretion of parathyroid hormone, which may lead to bone disease, bone pain and fractures, cardiovascular and soft tissue calcification, and parathyroid hyperplasia. Source: PRNewswire 6/26/10 

Last Patient Dosed and Database Locked in ED Trial

Palatin Technologies, Inc. in June announced the completion of patient dosing and database lock in a double-blind, placebo-controlled, multiple-dose, crossover study of bremelanotide, its subcutaneously administered melanocortin agonist for treatment of erectile dysfunction (ED). Palatin expects to report top-line data in the third quarter of 2010. The endpoints in the study are evaluation of plasma exposure and blood pressure, at rest and under exercise stress, in men between 45 and 65 years old, the target demographic. A total of 49 subjects were dosed in the study. Based on Palatin's internal review of the data and guidance from an external cardiovascular clinical advisory panel, Palatin intends to submit protocol proposals to the U.S. Food and Drug Administration for Phase II, at-home studies of subcutaneous bremelanotide in men with ED who are not responsive to phosphodiesterase-5 inhibitors such as Viagra®, a brand of sildenafil citrate. Phase II bremelanotide studies, designed to provide the data required to initiate Phase III registration studies, are planned to start as early as the fourth quarter of 2010. Bremelanotide, a synthetic peptide, is believed to act through activation of melanocortin receptors in the central nervous system. Nasal formulations of bremelanotide have been extensively studied, including Phase IIb studies for ED in both nondiabetic and diabetic patients and Phase IIa studies for female sexual dysfunction in both pre- and postmenopausal women. Increases in blood pressure observed in some patients receiving nasally administered bremelanotide, coupled with significant variation in plasma levels, lead to discontinuation of nasally administered bremelanotide as a first-line therapy for sexual dysfunction. Source: PRNewswire 6/24/10 

Pfizer Suspends Tanezumab Osteoarthritis Clinical Trial Program

Pfizer Inc. announced in June the suspension of the osteoarthritis clinical program for the investigational compound tanezumab following a request by the U.S. Food and Drug Administration (FDA). The worldwide suspension, which is effective immediately, follows a small number of reports of tanezumab patients experiencing the worsening of osteoarthritis leading to joint replacement. To date, this adverse event has not been observed in non-osteoarthritis patient populations taking tanezumab. The clinical hold includes both the suspension of recruitment of new patients and the dosing of existing patients in the osteoarthritis program, as well as patients with osteoarthritis in other studies. The FDA as asked that, later this week, the company present its assessment of the potential implications of the adverse events in the osteoarthritis program for the other tanezumab clinical programs involving non-osteoporosis patients, which include patients with cancer pain, interstitial cystitis, chronic low back pain and painful diabetic peripheral neuropathy. The company is actively working with the FDA, to determine the appropriate course of action, which will serve the best interest of patients. Source: PRNewswire 6/23/10 

Phase II Trial of Gene Therapy for Parkinson's Disease a Success

Neurologix, Inc. in June announced positive results in a Phase II trial of its investigational gene therapy for advanced Parkinson's disease (PD), NLX-P101. Study participants who received NLX-P101 experienced statistically significant and clinically meaningful improvements in off-medication motor scores compared to control subjects who received sham surgery. In the multicenter trial, this benefit was seen at one month and continued virtually unchanged throughout the six-month, double-blinded study period. The results also demonstrated a positive safety profile for NLX-P101, with no serious adverse events related to the gene therapy or surgical procedure reported. Patients enrolled in the trial had moderate to advanced PD and were not adequately responsive to current therapies. Neurologix's nondopaminergic approach uses an inhibitory gene (glutamic acid decarboxylase) to selectively alter the neural circuitry affected in PD and, thereby, normalize brain physiology. Neurologix's technology is the only gene therapy strategy currently in development that bypasses the dopamine system. NLX-P101 is delivered to the brain through a standard, minimally invasive surgical procedure that uses similar techniques to those currently employed in traditional surgery for PD. The Neurologix gene therapy procedure, however, does not require general anesthesia nor implantation of a permanent medical device in the brain. The primary measure of efficacy in the study was the difference in off-medication motor scores between the treated and sham groups on the Unified Parkinson's Disease Rating Scale Part 3 (Motor section). All subjects were evaluated at baseline as well as one, three, and six months after undergoing surgery. All treated subjects will continue to be monitored for safety for a 12-month period following their surgical procedure. Source: PRNewswire 6/22/10

Clinical Test Sites Selected for Portable Blood Analyzer

CardioGenics Holdings Inc. in June announced the selection of four sites for clinical testing of its patented QL Care™ Analyzer, a portable diagnostic platform designed to produce test results with central lab-like accuracy in 15 minutes using whole blood. The analyzer will be tested utilizing CardioGenics' Troponin-I test, the first in a series of four cardiovascular tests to be offered for use with the product. Troponin-I, a protein marker released into the blood by dying heart tissue, definitively confirms that a heart attack is in progress. The four selected sites--two in the U.S. and two in Canada--are active hospital emergency rooms that routinely admit patients presenting with chest pains. Blood samples will be drawn from approximately 50 patients at each site. One portion of each sample will be run on the hospital's central lab analyzer and the other on a CardioGenics QL Care Analyzer installed at the site, and the results will be compared. The goal is to confirm that the results from the company's analyzers and the central lab systems are the same. The head-to-head confirmation tests will commence during the third quarter of 2010, upon approval of the institutional review boards, and take approximately 45 days to complete. Upon successful completion of clinical confirmation, the company will finalize protocols and commence trials for an application to the U.S. Food and Drug Administration for approval of its analyzer and Troponin-I test. The testing is expected to start early in the fourth quarter of 2010 and be completed in two months. Source: PRNewswire 6/21/10 

Multiple-Dose Phase II Trial Initiated in Patients with Glaucoma

Inotek Pharmaceuticals Corp. in June announced that it has initiated dosing in a multiple-dose Phase II clinical trial to evaluate the efficacy and safety of its novel eye-drop INO-8875 in patients with glaucoma. In an earlier Phase I/II single ocular dose clinical trial, INO-8875 was shown to significantly reduce intraocular pressure (IOP) in glaucoma patients. As a highly-selective adenosine-1 receptor agonist, INO-8875 reduces IOP by enhancing a natural mechanism for clearing protein material that clogs the major outflow pathway--the trabecular meshwork--as the eye with glaucoma ages. The Phase II trial is a randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of INO-8875 delivered as an eye-drop formulation in patients with primary open-angle glaucoma or ocular hypertension. The trial includes multiple centers in the United States. In the earlier study of 84 patients, INO-8875 was well tolerated up to the highest dose tested, with no serious adverse events or observed dose-limiting toxicities. While the trial was not powered to achieve statistical significance, statistically significant reductions in IOP compared to placebo were attained at the two highest doses of INO-8875 tested. Source: Marketwire 6/17/10 

Malaria Vaccine Tested in Phase Ib in Children in Tanzania

Mymetics Corp. announced in June that its malaria vaccine has successfully completed a Phase Ib clinical trial in Tanzania. The study confirms that the company's virosome-based vaccine is well-tolerated and safe for adults and children as young as 5 years of age. The vaccine induced specific, long-lasting antibody responses against the key AMA-1 and CSP-1 malaria antigens in semi-immune subjects, lasting up to 12 months for CSP-1. It uses influenza-based virosomes as the antigen carrier--already approved as a vaccine carrier in more than 40 countries--with two synthetic peptide vaccine components that mimic the native structure of important antigens found during the key stages in the malaria parasite's life cycle. In the trial, conducted in cooperation with the Swiss Tropical and Public Health Institute and Pevion Biotech Ltd., the vaccine was tested during a 12-month period on 40 healthy, semi-immune volunteers (32 children, eight adults) in Tanzania under endemic conditions. Each subject received two injections. The results showed a high sero-conversion rate for most subjects. The vaccine is one of only a few that target the blood and liver stages of the malaria parasite's life cycle. Mymetics is now preparing the next phase of development of the multistage vaccine with additional promising malaria antigens, working closely with not-for-profit organizations. Source: Marketwire 6/17/10 

Center Added to Worldwide Clinical Trials for New Breast Imaging System

TechniScan in June announced that it has launched a clinical study in Rochester, Minn., its third new clinical site to commence in the last five months. TechniScan's Warm Bath Ultrasound (WBU) system is designed to capture three-dimensional images of the breast as a woman lies prone on a table and state-of-the-art ultrasound technology is used in a warm water tank to image the breast anatomy. This new method of imaging produces information and whole breast images that are not available with traditional reflection ultrasound or whole breast ultrasound systems presently on the market. To date, TechniScan has scanned more than 800 women in clinical studies in Salt Lake City and Ogden, Utah, as well as Orange and San Diego, California. These past clinical studies focused on key factors like image quality, repeatability, and establishing protocols for testing baseline values for positive and negative predictive capabilities of the system. According to the company, the most recently completed clinical work continues to support the goal that refraction-corrected reflection images highlight connective tissue features within the breast, whereas the speed-of-sound images show fibroglandular, ductal, and terminal lobular units with high resolution. Image consistency and reproducibility, whether it is weeks, months, or a year between exams, are critical to support precise and reliable assessment of breast lesions. Clinical studies in San Diego recently evaluated the ability of the system to reliably reproduce images from the same woman. Building on this prior clinical work, the current clinical studies in Freiberg, Germany, San Diego, and Rochester will involve at least 500 women with various types of breast lesions. Major objectives of the 12-month study will be to compare WBU to conventional breast sonography and MRI, as well as to examine the WBU system's ability to differentiate between normal, benign, and malignant breast tissue. These clinical studies in the U.S. are funded by a Small Business Innovation Research Grant from the National Cancer Institute. Source: PRNewswire 6/16/10 

Phase II Study Completed of Vaginal Insert to Reduce Delivery Time

Cytokine PharmaSciences, Inc. in June announced the completion of a Phase II study of the misoprostol vaginal insert (MVI), a proprietary, controlled-release, and retrievable polymer chip containing prostaglandin E(1) (PGE1). Results of the dose-finding study in pregnant women at term gestation confirm the efficacy and safety of this investigational product and suggest that the MVI may reduce time to delivery after induction, support more natural labor, and reduce the rate of cesarean delivery. The randomized, double-blind, multicenter study tested three doses of the MVI in 374 women undergoing cervical ripening and induction of labor at 11 sites across the U.S. The MVI 200 reduced time to vaginal delivery by more than nine hours compared to the lowest dose reservoir, MVI 100 (100 mcg reservoir). Oxytocin use was required in less than half the women tested with the MVI 200, and women exposed to this dose also spent an average of eight hours less in the labor and delivery suite compared to MVI 100. Safety was primarily assessed by frequency of cesarean section--22.9 percent for the MVI 200 compared to 31.4 percent for the MVI 100. Immediate neonatal outcomes were similar across the three dose reservoirs tested, and showed no safety signals of concern. A Phase III study in patients requiring cervical ripening and induction of labor is planned for the second half of 2010. Source: PRNewswire 6/15/10 

Phase I Trial Initiated for Lead Anticalin Compound

Pieris AG announced in June the initiation of a Phase I clinical trial in cancer patients for its lead program, PRS-050, an anti-VEGF anticalin. The trial is an open-label, dose-escalating evaluation of the compound's safety and tolerability in patients with solid tumors. Conducted at three sites in Germany, the trial is under way and patients from the first cohort have been dosed. The trial is designed to test PRS-050 in approximately 40 patients, who will receive the compound and then be monitored for safety and tolerability. The patients recruited for the trial are cancer patients with advanced, recurrent, or metastatic solid tumors, refractory to standard therapy. PRS-050 is an anti-VEGF (Vascular Endothelial Growth Factor) anticalin discovered and developed internally at the company from the company's proprietary anticalin libraries. PRS-050's mechanism of action is based on its ability to bind the VEGF ligand, thereby inhibiting tumor growth. VEGF's role in cancer angiogenesis, the mechanism by which cancer tumors increase blood vessel development to deliver key nutrients and oxygen, is well established, both scientifically and clinically. Source: PRNewswire 6/15/10

Drug that Prevents Clot Breakdown Could Save Thousands of Accident Victims

Tranexamic acid (TXA)—a cheap, widely available, and easily administered drug that reduces the rate of blood-clot breakdown—could save the lives of thousands of accident victims worldwide. The CRASH-2 study, published online and in an upcoming Lancet, also concludes that TXA should now be included on the World Health Organization list of essential medicines. The article is written by Prof. Ian Roberts and Dr. Haleema Shakur, London School of Hygiene and Tropical Medicine, United Kingdom, and colleagues from the CRASH-2 consortium. Part of the response to surgery and trauma is stimulation of clot breakdown (fibrinolysis). TXA works by inhibiting the enzyme that carries out fibrinolysis. The authors proposed that TXA might reduce mortality due to bleeding in trauma patients; however, until now there have been no randomized trials of this drug in such patients. Thus, in CRASH-2, the authors assessed the effects of the early administration of a short course of TXA in trauma patients. The trial was funded by England's National Institute for Health Research Health Technology Assessment program and was a large, randomized trial involving more than 20,000 adult patients in 274 hospitals across 40 countries. Participants received either one gram of TXA by injection, followed by another one gram in a drip over the following eight hours, or a matching placebo. The researchers studied the numbers of deaths in hospital within four weeks of injury. TXA reduced the risk of death by any cause by 10 percent compared to placebo, with 14.5 percent of patients in the TXA group dying versus 16 percent in the placebo group. Looking specifically at the risk of death due to bleeding, TXA reduced the risk of death by 15 percent compared to placebo, with 4.9 percent of patients in the TXA group dying versus 5.7 percent in the placebo group. Although the research team was concerned that TXA might increase the risk of complications, such as heart attacks, strokes, and clots in the lungs, the results of CRASH-2 show that TXA reduces death from bleeding without any increase in these complications. Furthermore, the researchers are excited about other potential future applications of TXA, such as reduction of brain bleeds after brain injury, for which new studies are needed. TXA could also be used for reduction of postpartum haemorrhage in women worldwide, which causes around 100,000 deaths each year. A large trial to assess TXA for this purpose is in progress. Source: EurekAlert! 6/14/10 

Lung Cancer Treatment Does Not Meet Primary Endpoint in Phase III

Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc. in June announced that the final analysis of the Phase III NExUS (NSCLC research Experience Utilizing Sorafenib) trial evaluating Nexavar® (sorafenib) tablets in patients with advanced non-squamous non-small cell lung cancer (NSCLC) showed that the study did not meet its primary endpoint of improving overall survival in the first-line setting. NExUS evaluated Nexavar versus placebo in combination with two chemotherapeutic agents, gemcitabine and cisplatin. The study enrolled approximately 900 patients from sites throughout Europe, South America, Asia Pacific and the Middle East. A positive secondary endpoint of progression-free survival (PFS) was observed in the trial. The safety and tolerability of the treatment triplet was as expected, and did not show any new or unexpected toxicities. Data from this study are expected to be presented at an upcoming scientific meeting. Nexavar is currently marketed worldwide for the treatment of hepatocellular carcinoma, or liver cancer, and advanced renal cell carcinoma, or kidney cancer. Enrollment in NExUS commenced in February 2007. In 2008, based on the results seen in a previous Nexavar first-line NSCLC Phase III trial, the NExUS study protocol was amended to stop enrolling and treating squamous cell carcinoma patients. Of the squamous cell patients who were enrolled in the NExUS trial before the amendment, a higher mortality was observed. This finding was consistent with what was seen in the previous trial. Bayer and Onyx will further review the findings of this analysis to determine what, if any, impact these data might have on other ongoing clinical trials evaluating the safety and efficacy of Nexavar. "Bayer and Onyx are disappointed with these results, in particular, for patients who are suffering from this deadly disease," said Dr. Dimitris Voliotis, vice president for global clinical development oncology at Bayer HealthCare. "We are confident in our clinical trial program exploring Nexavar's potential in a variety of tumor types, including lung cancer. Based on encouraging data from a recently presented prospective biomarker trial and Phase II signal-generating lung cancer studies, we believe it's critical to continue our evaluation of Nexavar in combination with targeted agents and as a monotherapy in later lines of treatment in lung cancer patients." Nexavar is being evaluated by the companies and individual investigators in a variety of treatment settings for patients with non-small cell lung cancer, including a Phase III monotherapy study in the third- and fourth-line setting and Phase II studies in combination with other therapies in the second-line setting. Source: PRNewswire 6/14/10

Inexpensive Drug to Stop Sight Loss Shown to be Effective

An inexpensive, but unlicensed drug to help prevent severe sight loss in older people has been shown to be safe and effective, finds a study published on bmj.com in June. Bevacizumab (Avastin) is licensed as a treatment for bowel cancer, but it is widely used "off label" as a considerably cheaper alternative to the approved drug ranibizumab (Lucentis) to prevent wet age-related macular degeneration (AMD), and several large trials comparing the two drugs are now under way. In the majority of countries in the world, where either no treatment or inferior therapies are available to patients with wet AMD, the appropriate use of bevacizumab, a highly cost-effective intervention, would have an immediate impact in reducing incident blindness from this condition, the researchers say. In 2006, researchers based at three United Kingdom eye centers set out to test whether bevacizumab is an effective and safe treatment for wet AMD compared to standard Natioal Health Service (NHS) care available at the time. A total of 131 patients aged at least 50 years with wet AMD were randomized to either bevacizumab injections at six-week intervals or standard care (one of three different treatments available on the NHS at the start of the study). Visual acuity was measured at the start of the study (baseline) and then monitored over one year (54 weeks). At one year, 32 percent of patients in the bevacizumab group gained 15 or more letters from baseline visual acuity, compared to 3 percent in the standard care group. In addition, the proportion of patients who lost fewer than 15 letters of visual acuity from baseline was significantly greater among those receiving bevacizumab treatment (91 percent), compared to 67 percent in the standard care group. Average visual acuity increased by seven letters in the bevacizumab group with a median of seven injections compared to a decrease of 9.7 letters in the standard care group, and the initial improvement at week 18 was sustained to week 54. In an accompanying editorial, Prof. Usha Chakravarthy from the Royal Victoria Hospital in Belfast says that, although this trial fills a gap in the evidence base and shows robustly that bevacizumab is better than previously employed treatments, it does not show whether the drug is as effective as ranibizumab. She warns that "the off label use of bevacizumab should not be encouraged until the large randomized trials comparing it [to] ranibizumab report their findings." Source: EurekAlert! 6/10/10 

Data Show Promising Oral Efficacy of Treatment for Acute Migraine Attacks

CoLucid Pharmaceuticals, Inc. in June announced that its investigational first-in-class Neurally Acting Anti-Migraine Agent (NAAMA), lasmiditan (also known as COL-144), a selective 5-HT1F receptor agonist, was effective when given orally to treat acute migraine attacks, as documented in a Phase IIb study. Results of this study will allow the selection of doses for pivotal Phase III studies of lasmiditan in the acute treatment of migraine, scheduled to begin in the fourth quarter of this year. In the recently completed double-blind, randomized, placebo-controlled, parallel-group, dose-ranging study conducted in five European countries, 391 patients treated a single migraine attack with one of four doses of lasmiditan or placebo. The study met its primary endpoint, showing a highly significant correlation between dose and headache relief at two hours. Individual doses showed significant benefit compared to the placebo from as early as 30 minutes after treatment. Lasmiditan also provided significant relief of other migraine symptoms, as measured in the study, including nausea, photophobia, and phonophobia. Dizziness and fatigue were the most common adverse events reported in the study. No clinically significant adverse effects were identified in either the laboratory parameters or electrocardiography. Cardiovascular adverse events, including chest symptoms experienced with the current migraine medication group known as triptans, were rare and occurred with similar frequency in the placebo and active treatment groups. The investigators intend to submit a complete data analysis for peer-review publication or presentation. Source: EurekAlert! 6/9/10 

First Safety Trial in Africa of Vaginal Ring Designed to Prevent HIV/AIDS

The nonprofit International Partnership for Microbicides (IPM) in June announced the initiation of the first trial among women in Africa testing a vaginal ring containing an antiretroviral drug (ARV) that could one day be used to prevent HIV transmission during sex. The clinical trial, known as IPM 015, tests the safety and acceptability of an innovative approach that adapts a successful technology from the reproductive health field to give women around the world a tool to protect themselves from HIV infection. The vaginal ring used in IPM 015 is made of flexible silicone, is durable and would be easy to distribute--making it well suited for use in developing countries. Each ring slowly releases 25 mg of the ARV drug dapivirine over the course of 28 days, potentially providing sustained protection against HIV. The ring is manufactured by IPM, which has a royalty-free license for dapivirine from Tibotec Pharmaceuticals, a division of Johnson & Johnson. IPM 015 is a Phase I/II expanded safety trial that will compare the dapivirine ring with a placebo ring containing no active drug among 280 volunteers across Africa. Women in South Africa have begun volunteering for the trial, and it is hoped that other African nations will start the same study shortly. The women volunteers will be randomly assigned to use either the dapivirine or the placebo ring, which will be replaced once monthly for a three-month period. The vaginal ring containing dapivirine has already been shown to be safe as tested in four prior IPM clinical trials among women in Europe, with another trial ongoing. If IPM 015 further confirms the safety and acceptability of the product among women in Africa, a Phase III program to test the ability of dapivirine rings to prevent HIV infection is scheduled to begin in Africa in 2011, with results due in 2015. Source: PRNewswire 6/8/10 

Phase IIb Results Show Treatment's Effectiveness in Eosinophilic Asthma

Aerovance Inc. in June announced top-line results from its Phase IIb clinical trial that show the inhaled dry powder formulation of Aerovant (pitrakinra inhalation powder) is effective in a predefined subset of patients with eosinophilic asthma. Data from AeroTrial™, a 534-patient, double-blind, randomized, placebo-controlled, dose-ranging study, showed a 37 percent reduction in the incidence of asthma exacerbations in patients on Aerovant 10 mg twice-daily treatment compared to placebo in the subset of patients (n = 125) with eosinophilic asthma, as measured by elevated blood eosinophils. Time to exacerbation and asthma symptom scores also improved significantly compared to placebo in the same patient population. In the broader study population of moderate-to-severe asthmatics (eosinophilic plus non-eosinophilic asthmatics), there was no statistically significant difference between Aerovant and placebo, although Aerovant 10 mg (highest dose) did show trends towards drug effect. Overall, Aerovant was safe and well-tolerated in this study. Aerovance plans to present a complete summary of the results at the European Respiratory Society congress in Spain this September. AeroTrial was conducted at 75 sites in the United States and Europe. In the study, patients with moderate-to-severe asthma who were inadequately controlled on the combination of inhaled corticosteroids (ICS) and long-acting beta agonists (LABA) were assigned to receive one of three doses (1 mg, 3 mg, or 10 mg) of Aerovant or placebo by inhalation twice-daily for 12 weeks. During this time, the standard ICS and LABA therapies were gradually withdrawn. The trial is the largest clinical study to date of an IL-4/IL-13 inhibitor, a compound that targets a root cause of the inflammatory cascade in asthma. Source: PRNewswire 6/8/10 

Clinical Promise Seen in Patients with Advanced Hormone Refractory Breast Cancer

Syndax Pharmaceuticals, Inc. reported final results from the Phase II, open-label ENCORE 303 trial of entinostat in post-menopausal women with advanced, estrogen receptor (ER) positive breast cancer who were progressing on aromatase inhibitor (AI) therapy. Safety and efficacy results from the trial were presented in a poster at the American Society of Clinical Oncology annual meeting in Chicago in early June. "These findings are significant, given that the patients enrolled were heavily hormonally pretreated and relatively hormone resistant," said Joanna Horobin, president and CEO of Syndax. "Resistance to AI therapy is multifactorial and involves up-regulation of growth factor signaling pathways and down-regulation of estrogen receptor expression, which may result from epigenetic modifications to the DNA and associated proteins. The disease stabilization achieved with the addition of entinostat supports our hypothesis that entinostat has the ability to normalize gene expression, thereby restoring sensitivity to targeted agents. We are optimistic that our ongoing ENCORE 301 study, a double-blind, randomized, placebo-controlled Phase II study of entinostat in combination with the aromatase inhibitor exemestane, will provide further evidence supporting the clinical benefit and tolerability of entinostat in combination with aromatase inhibitors." The primary endpoint of the study was Clinical Benefit Rate (CBR), defined as the proportion of patients who experience a complete or partial response or stable disease during the first six cycles of study treatment. Of the 26 evaluable patients in the ENCORE 303 study, one achieved a partial response and three achieved stable disease of greater than six months. The CBR of 15.4 percent exceeded the prespecified rate of 5 percent defined in the study design with a p-value of 0.039. An additional six patients experienced stable disease between four and six months. Secondary endpoints were objective response and progression-free survival, which were 3.9 percent and a median of 4.8 months, respectively. Overall survival, pharmacokinetics, and correlation of selected biomarkers with clinical outcome were also measured. The most common adverse events considered to be related to entinostat were fatigue, nausea, and diarrhea. No unexpected side effects were observed. Source: PRNewswire 6/4/10

Positive Phase III Results Announced for Fibroid Treatment

PregLem in June announced positive Phase III data from its second pivotal study (PEARL I) for its lead product Esmya (ulipristal acetate), as an effective treatment for uterine fibroids (myoma)--a condition that affects millions of women worldwide. The final set of positive Phase III results, combined with the positive PEARL II results announced in May 2010, will enable PregLem to submit a Marketing Authorization Application to the European Medicines Agency by the end of 2010. Upon approval, PregLem expects to launch the product in major European markets. PEARL I was designed to demonstrate superior efficacy of Esmya versus placebo for the treatment of symptomatic uterine fibroids in women with heavy bleeding leading to anemia. It was a randomized, parallel-group, double-blind, placebo-controlled, multicenter study with a total of 242 patients. It compared 5 mg and 10 mg doses of Esmya and placebo once daily for three months with concomitant iron administration in all three arms. The study met its two co-primary efficacy endpoints. Esmya demonstrated statistically significant superior efficacy to placebo in reducing excessive uterine bleeding measured as a percentage of patients with a reduction of PBAC (Pictorial Blood Assessment Chart) score lower than 75 and in reduction of total fibroids volume assessed by centralized MRI reading. Esmya also showed superior efficacy to placebo in correcting anemia caused by uterine fibroids and suppressing fibroids-related pain using the McGill Short Form questionnaire (SF-MPQ). Both the PBAC and SF-MPQ are validated self-reporting tools. Source: PRNewswire 6/3/10

Drug Meets Primary Endpoint for Advanced Pancreatic Neuroendocrine Tumors

Novartis Pharmaceuticals Corp. announced in June that a Phase III study of Afinitor® (everolimus) tablets plus best supportive care met its primary endpoint, showing the drug significantly extended progression-free survival, or time without tumor growth, in patients with advanced pancreatic neuroendocrine tumors (NET). The study, RADIANT-3 (RAD001 In Advanced Neuroendocrine Tumors), is part of the largest clinical trial program of its kind. Everolimus is approved under the trade name Afinitor tablets for the treatment of patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib. Pancreatic NET can grow aggressively and at time of diagnosis nearly 60 percent of all patients have advanced disease, meaning the cancer has spread to other parts of the body and has become more difficult to treat. The median survival rate for patients with advanced pancreatic NET is 17 months. Currently, surgery and chemotherapy are the only approved treatment options for patients with advanced pancreatic NET. Full results from the RADIANT-3 study will be submitted for presentation at the European Society for Medical Oncology annual meeting taking place in Milan, Italy, in October. Additionally, worldwide regulatory filings are planned for 2010. RADIANT-3 is a prospective, double-blind, randomized, parallel-group, placebo-controlled, multicenter study. The trial examined the efficacy and safety of everolimus plus best supportive care versus placebo plus best supportive care in 410 patients with advanced pancreatic NET, also known as islet cell tumors. Patients who met the study's entry criteria were randomized 1:1 to receive either daily everolimus (10 mg) or daily placebo orally. The primary endpoint of RADIANT-3 is progression-free survival. Secondary endpoints include safety, objective response rate, and overall survival. Source: PRNewswire 6/3/10

Investigation of New Treatment Protocol for Alzheimer's Disease Initiated

Grifols, SA announced at its annual meeting with investors and analysts, that it will initiate a new clinical investigation of Alzheimer's disease in January 2011 with an anticipated enrollment of more than 300 patients. The new clinical investigation involves a combined treatment of therapeutic plasmapheresis and the administration of human albumin and intravenous immune globulin (IVIG) at different doses and frequencies. Human albumin and IVIG are two of the main therapeutic plasma proteins Grifols' produces from donations of human blood plasma at dedicated donation centers across the United States. In conjunction with the announcement of the new clinical investigation, Grifols also announced that it has entered into an exclusive design and development agreement with U.S.-based Fenwal, Inc. for the production of a prototype plasmapheresis device specifically adapted for use in Grifols' Alzheimer's research. Fenwal is expected to deliver the first prototype devices at the end of this year. It is anticipated that the 2011 study will take place over the course of two years. In September 2009, Grifols published the interim results of a clinical trial including 42 patients from three hospital research centers in Spain and two in the United States. That study involved therapeutic plasmapheresis and the administration of human albumin. The preliminary results suggested a trend toward disease stabilization in the treatment group. The newly announced clinical investigation builds off of the results of the prior study by expanding the number of subjects and altering the treatment regimen. Source: PRNewswire 6/2/10

Final Results Announced from Halted Phase III Trial of Anticancer Therapeutic

Marshall Edwards, Inc. announced in early June that a final analysis of its Phase III OVATURE trial of orally administered phenoxodiol in women with recurrent ovarian cancer determined that the trial did not show a statistically significant improvement in its primary (progression-free survival) or secondary (overall survival) endpoints. As previously announced, the trial was closed for recruitment before completion of enrollment with only 142 out of a planned 340 patients enrolled. The multicenter, randomized, double-blind trial assessed the safety and efficacy of daily phenoxodiol in combination with weekly carboplatin versus weekly carboplatin with placebo in patients with platinum-resistant or platinum-refractory, late-stage epithelial ovarian, fallopian, or primary peritoneal cancer following at least second-line platinum therapy. "Owing to the fact that this trial was significantly underpowered due to the small number of patients enrolled, we were disappointed, but not entirely surprised by the final outcome," said Dr. Daniel P. Gold, newly appointed CEO of Marshall Edwards. "However, we remain confident that our investigational isoflavone platform, including triphendiol, a potentially more potent, second-generation analogue of phenoxodiol, may be of benefit to women with ovarian cancer, particularly when administered intravenously. Previously reported results of a Phase II trial, which tested the activity of intravenous phenoxodiol plus weekly cisplatin in a similar platinum-resistant or refractory patient population, demonstrated a 30 percent response rate (six out of 20) compared to less than 1 percent (one out of 142) in the OVATURE study, in which phenoxodiol was administered orally. In addition, we remain excited with the progress of another product candidate in our pipeline, NV-128, a novel isoflavone analogue with a mode of action distinct from both phenoxodiol and triphendiol. Lastly, I want to take this opportunity to personally thank the patients and their families for their participation in this trial. I would also like to thank the clinical investigators and trial coordinators for their dedication and support." Phenoxodiol had a good safety profile and was well-tolerated. The number of patients experiencing at least one adverse event was similar in each treatment group, as was the number of patients experiencing adverse events of Grade 3 or higher. Changes in standards of care over the period of the trial and the stringency of inclusion/exclusion criteria of the OVATURE protocol had slowed patient recruitment rates and, consequently, the company deemed it prudent not to continue the trial to completion. The independent data monitoring committee supported the company's decision to close the study to accrual, and, in a review of the available safety data, confirmed that there were no safety concerns with phenoxodiol in these subjects. Source: Marketwire 6/1/10

Pivotal Data Presented for Primary Premature Ejaculation Spray

Shionogi Pharma, Inc. in early June presented data summarizing the results of two pivotal studies of the investigational new drug PSD502, a topical metered dose spray being developed for the treatment of primary premature ejaculation (PE). These data were presented at the 2010 American Urological Association Annual Meeting in San Francisco, Calif. Evaluating a combined total of 556 (randomized) and 536 (treated) men with primary PE in the United States, Canada, and Europe over a three-month period, with more than 23,000 exposures to PSD502 recorded, the data demonstrated that men who were treated with PSD502 five minutes before intercourse by applying PSD502 via a topical metered dose spray had a time to ejaculation 5.5 times longer than those who used a placebo spray with the actual average measurement in minutes for drug and placebo. A co-primary endpoint also looked at ejaculatory control and satisfaction. Point differences of 6.1 and 5.3 were observed between the PSD502 group and placebo in ejaculatory control and satisfaction domains, respectively. Men selected from 70 centers with primary PE and an Intravaginal Ejaculatory Latency Time (IELT) of less than one minute were randomly placed in one of two groups, two-thirds in the PSD502 group and one-third in the placebo group. Participants were instructed to apply PSD502 or placebo to the glans penis five minutes before intercourse. Efficacy was assessed from changes in IELT and in the domains of the Index of Premature Ejaculation (IPE), a patient reported outcome questionnaire, over a period of three months. The baseline IELT in both study groups was less than 0.6 minutes which increased 5.5 fold and 1.6 fold in the PSD502 and placebo groups, respectively, resulting in a mean IELT of 3.3 minutes in the PSD502 group. There were greater improvements in all domain scores of the IPE in the PSD502 group compared to placebo, resulting in 6.1, 5.3, and 2.6 point differences between PSD502 and placebo in ejaculatory control, satisfaction and distress domains respectively. PSD502 is a proprietary formulation of the two marketed drugs, lidocaine and prilocaine. Source: Newswise 6/1/10

Researchers Find Papillary Renal Cell Carcinoma Unresponsive to Standard Treatment

Of the more than 38,000 Americans diagnosed with renal cell carcinoma (RCC) each year, approximately 20 percent have non-clear cell forms of the disease. New findings shows that a non-clear cell form of kidney cancer known as papillary RCC, which accounts for 12 percent of all RCC, responds differently to sunitinib--a standard frontline treatment for RCC. In a small but decisive Phase II trial, the researchers found that sunitinib was not effective in patients with this form of the disease. The terms clear-cell and non-clear cell refer to the general appearance of the cancer cells under a microscope. The study's lead investigator from the University of Texas MD Anderson Cancer Center reported the results at the 46th Annual Meeting of the American Society of Clinical Oncology on June 7. The research team examined the response and survival rates of 23 patients with papillary RCC who were treated with sunitinib. The study built upon prior research that showed a high response rate and improved progression-free survival and overall survival in patients with clear-cell RCC who used sunitinib to interfere with the growth of cancers cells, either slowing or stopping the development of tumors. In the current study, patients with papillary RCC were treated with sunitinib according to a two-stage design. Following the sunitinib regimen, researchers found no major responses, a median progression-free survival of 1.6 months, and median overall survival of 10.8 months. The best response was stable disease in eight patients. The results underscore the need to develop more effective therapies for papillary RCC. Funding for this investigator-initiated study was provided by Pfizer. Source: EurekAlert! 5/28/10

Trial Halted to Recruitment Due to Significant Benefit Observed for Heart Patients

Pfizer Inc. in late May announced that it plans to halt recruitment to the Phase IIIb EMPHASIS-HF trial early on the recommendations of the trial’s independent executive steering committee. The recommendations follow a second interim analysis by the independent data safety monitoring committee of the EMPHASIS-HF trial confirming the study has reached its primary efficacy endpoint early, according to the protocol predefined stopping rules. The interim analysis showed that patients treated with Inspra® (eplerenone), in addition to current standard of care, experienced a significant reduction in risk of cardiovascular (CV) death or heart failure (HF) hospitalization compared to those on the placebo arm of the trial, where patients received standard of care in addition to a matching placebo. Based upon the interim analyses by the independent data safety monitoring committee, eplerenone, generally, was well tolerated during the EMPHASIS-HF trial. The EMPHASIS-HF trial was a double-blind, placebo-controlled, parallel-group trial, set for 270 centers in approximately 30 countries, comparing the effect of eplerenone plus standard heart failure therapy versus placebo plus standard heart failure therapy on mortality and morbidity outcomes in patients with mild chronic systolic heart failure (NYHA functional Class II) and left ventricular systolic dysfunction. The composite primary endpoints were the first occurrence of either CV death or HF hospitalization. The EMPHASIS-HF trial was to enroll approximately 3,100 patients and was to continue until a total of 813 adjudicated primary endpoint events were reported. Inspra does not have a licence for use in the patient population studied in the EMPAHSIS-HF trial in any individual market. The trial had an estimated end date around October 2011. Pfizer has informed the relevant regulatory agencies, ethics committees/independent review boards, and investigators as appropriate in countries where the trial was being conducted, and continues to work with the data safety monitoring committee, executive steering committee, and all study investigators globally. In addition, Pfizer is working to ensure all patients are informed via their clinicians, and an amendment to the protocol will be requested in order to allow all consenting patients to start treatment with eplerenone in an open-label extension of the study, after completing a close-out visit ending the double-blind, placebo-controlled phase. Source: Pfizer press release 5/27/10

Investigator-Sponsored Trial Launched for Stent System

Boston Scientific Corp. in May announced the initiation of the PLATINUM PLUS clinical trial, an investigator-sponsored research study designed to compare the performance of the Promus® Element™ everolimus-eluting coronary stent system to the Xience Prime™ everolimus-eluting coronary stent system. The Promus Element stent, which received CE Mark in October 2009, is Boston Scientific's third-generation drug-eluting stent technology, and incorporates a platinum chromium alloy into the design and catheter delivery system. PLATINUM PLUS is a prospective, randomized, multicenter clinical trial with planned enrollment of 2,980 patients at 50 sites in France, Germany, Italy, Spain, and the U.K. It will evaluate coronary revascularization outcomes in an unrestricted patient population randomized (2:1) to receive a Promus Element stent or Xience Prime stent. The primary endpoint is 12-month target vessel failure with planned follow-up out to 34 months. The trial is funded by a research grant from Boston Scientific. Results are expected to be presented in 2012. Source: PRNewswire 5/26/10

Top-Line Results from Modified Phase IIb Stroke Trial Show Surprising Placebo Response

Stem Cell Therapeutics Corp. announced in May the top-line results for the modified REGENESIS-Phase IIb stroke trial. The placebo-controlled, double-blinded, 3:1 randomized clinical study enrolled 96 patients with acute ischemic stroke between August 2009 and January 2010. The company reports that the top-line primary endpoint results for the trial of NTx®-265 in acute stroke showed that there was substantial improvement in the primary endpoint absolute change in NIHSS in both placebo-treated patients and those receiving NTx-265, with no statistical differences between the groups. "The profile and magnitude of the placebo response is extremely surprising and merits further examination" said Dr. Alan Moore, CEO and president of Stem Cell Therapeutics. "We are currently conducting a validation review process of the full trial. We expect to report on the outcome of this within the next two to three weeks, together with results from a number of secondary endpoints, such as modified Rankin and Barthel index, which may provide an alternative to NIHSS as a pathway forwards." The results show that NTx-265 was well tolerated in treated patients with no adverse affect on mortality. Of the 96 patients enrolled in the trial, 72 were administered a course of NTx-265, sequential administration of human chorionic gandotropin followed by erythropoietin, with the first dose at 24-48 hours after stroke onset, while 24 patients were treated with placebo. All patients were then monitored for 90 days. The top-line data show that the NTx-265 treated group showed a drop of 6.3 +/- 0.5 NIHSS compared to placebo drop of 7.3 +/- 0.9 NIHSS. This difference was not statistically significant. Additionally, none of the individual dose groups showed a statistically significant effect compared to placebo. Source: Marketwire 5/25/10

Company Provides Update on Phase I Progress of ALS Treatment

Neuralstem, Inc. in May updated the progress of its ongoing Phase I human clinical trial to treat ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease) at Emory University in Atlanta, Ga. The company announced that, after reviewing the safety data from the first cohort of three patients, the safety monitoring board has approved moving to the next cohort and transplantation of the fourth patient. The first cohort of patients received five injections of the company's spinal cord stem cells on one side of the spinal cord. The second cohort of three patients will receive ten injections, five on each side of the cord. The Food and Drug Administration-approved trial to evaluate the safety of Neuralstem's spinal cord stem cells in the treatment of ALS has been under way since January 2010. The trial will ultimately consist of up to 18 ALS patients, who will be examined at regular intervals post-surgery, with final review of the data to come six months after the last patient is treated. The Emory ALS Center has posted the relevant trial information for patients here. Source: EurekAlert! 5/24/10

Data Show Extended-Release Tablets with Stimulants Provided ADHD Symptom Improvement

Shire plc in May announced new findings on once-daily Intuniv™ (guanfacine) extended-release tablets, the first selective alpha-2A agonist approved for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), at a major psychiatric meeting. The primary objective of this study was to evaluate the efficacy of Intuniv, dosed either in the morning or evening, compared to placebo, when co-administered with stimulant medications used to treat ADHD in children and adolescents ages 6 to 17 with ADHD and suboptimal response to stimulant alone. The study met its primary end point, which was the change from baseline to end point in the ADHD Rating Scale-IV (ADHD RS-IV) total score. The U.S. Food and Drug Administration (FDA) approved Intuniv in September 2009 as an ADHD treatment for children and adolescents ages 6 to 17, based on two pivotal monotherapy studies. The data presented in May were included as part of a supplemental New Drug Application submitted to the FDA on April 28 to seek approval for the drug as adjunctive treatment with long-acting oral stimulants for the treatment of ADHD in this patient population. Throughout the nine-week, randomized, double-blind, placebo-controlled, parallel-group, dose-optimized Phase III study, patients continued to take their same once-daily dose of a long-acting stimulant and were randomized to three treatment arms: Intuniv dosed in the morning, Intuniv dosed in the evening, or placebo. A total of 455 patients were evaluated for efficacy and safety. The study consisted of five weeks of dose optimization and three weeks of dose maintenance. Intuniv was optimized up to 4 mg per day. At baseline, mean ADHD RS-IV total scores were 37.6, 37.0, and 37.7 for the Intuniv AM/stimulant, Intuniv PM/stimulant, and placebo/stimulant treatment groups, respectively. At study end, mean ADHD RS-IV total scores were 17.3, 16.1, and 21.7, respectively. Source: PRNewswire 5/21/10

New Data Presented on Advanced Melanoma Agent

Lilly released results in May from a Phase II study evaluating Lilly Oncology's tasisulam, a novel anticancer agent, in patients with metastatic melanoma, the deadliest form of skin cancer. Study results will be presented during the 46th Annual Meeting of the American Society of Clinical Oncology in Chicago, Ill., on June 6. The study evaluated the use of tasisulam as a second-line treatment in patients with unresectable or metastatic melanoma. The trial's primary objective was to determine overall response rate and its two secondary objectives were to determine progression-free survival and overall survival. Of the 68 patients enrolled in the study, eight demonstrated partial response, 24 had stable disease (no progression after two cycles), 25 had progressive disease, and 11 did not have their disease progression completely evaluated. The median progression-free survival was 2.6 months and the median overall survival was 9.6 months. Tasisulam was given in 21-day cycles using a dosing algorithm based on body weight. The most common grade 3/4 hematologic toxicities were thrombocytopenia (low platelet count), neutropenia (low white blood cell count), and anemia (low red blood cell count). Nonhematologic toxicities included fatigue, mucositis (inflammation of the mucous membrane), and stomatitis (inflammation of the mucous lining). Source: PRNewswire 5/20/10

Promising Interim Results from Pilot Study in Severe Nocturnal Asthma

Horizon Pharma, Inc. in May announced interim results from a pilot clinical study showing that Lodotra® (modified-release prednisone tablet) chronotherapy may improve asthma control and asthma-related quality of life when added to standard asthma therapy in patients with severe nocturnal asthma. The data were presented during a poster session at the American Thoracic Society 2010 International Conference in New Orleans, La. The MONA (modified-release prednisone for the treatment of nocturnal asthma) study is a two-stage, open-label, pilot trial assessing Lodotra's treatment effect in patients with severe nocturnal asthma who require treatment with oral prednisone in addition to standard asthma therapy. After a two-week screening period, patients were treated with immediate-release prednisone at 8 a.m. for four weeks, and then switched to four weeks of the same dose in the evening prior to sleep. The primary endpoint of the study was the number of nocturnal awakenings due to asthma in treated patients. Secondary endpoints include asthma control questionnaire responses, asthma quality of life questionnaire responses, and general safety. Data from five patients treated with 5 to 45 mg of daily prednisone in accordance with the study protocol showed clinically relevant improvements in nocturnal symptoms, asthma control, and asthma-related quality of life. The number of nocturnal awakenings changed from 9.2 + 6.3 (standard deviation) with immediate-release prednisone to 2.6 + 5.3 under treatment with Lodotra chronotherapy in the last two weeks of each respective treatment period. General asthma control improved from a mean of 3.2 in the last week of patients receiving immediate-release prednisone, to a mean of 2.0 in the last week of Lodotra therapy. Asthma-related quality of life improved from a mean of 3.9 in the last week of immediate release prednisone treatment to a mean of 4.9 in the last week of Lodotra therapy. The median number of as-needed inhalations of salbutamol per day decreased from 2.1 during the immediate-release prednisone treatment period to 1.0 during the Lodotra treatment period in the last two weeks of each respective treatment period. The incidence of adverse events was low throughout the study and comparable between the two treatment periods. The MONA study is expected to complete enrollment of patients in the third quarter of 2010. Source: PRNewswire 5/19/10

Phase III Bodes Well for Treatment of Pre-Menopausal Women with HSDD

Data from pivotal Phase III clinical trials demonstrate that a higher proportion of pre-menopausal women with Hypoactive Sexual Desire Disorder (HSDD) receiving flibanserin 100 mg reported both an improvement in their condition and a meaningful benefit from their treatment, compared to placebo. Flibanserin is an investigational compound being developed by Boehringer Ingelheim Pharmaceuticals, Inc. HSDD is a persistent or recurrent decrease or lack of sexual desire that causes distress for the patient, may put a strain on relationships with partners, and is not due to the effects of a substance, including medications, or another medical condition. The findings, presented at the 58th Annual Clinical Meeting of the American College of Obstetricians and Gynecologists in San Francisco, Calif., include data from a pre-specified pooled analysis of two pivotal North American trials (DAISY® and VIOLET®) totaling 1,378 subjects. "These new data offer a unique perspective on the effects of flibanserin 100 mg from the patient's point of view. Not only did pre-menopausal women with HSDD report feeling an improvement in their symptoms of low desire and associated distress when taking flibanserin, but they also reported that this change had a meaningful benefit to them," said John Thorp, MD, study investigator and professor of obstetrics and gynecology at the University of North Carolina Medical School. These findings add to data from the primary and secondary endpoint analysis of flibanserin pivotal trials. According to the pre-specified pooled analysis of women who completed 24 weeks of treatment, flibanserin 100 mg showed statistically significant improved measures of sexual desire, overall sexual functioning, distress associated with low sexual desire, and the number of satisfying sexual events, compared to placebo. By 24 weeks, 48.3 percent of women receiving flibanserin and 30.3 percent of women receiving placebo reported feeling very much improved, much improved, or minimally improved. In addition, more women in the flibanserin group versus placebo reported experiencing a meaningful benefit from the study medication (40.5 percent versus 25.2 percent, respectively). Source: EurekAlert! 5/18/10

Implanted Sleep Device Shows Promising Early Results

Apnex Medical announced in May that preliminary data from an Australian first-in-human clinical study showed significant improvements in sleep for people suffering from obstructive sleep apnea (OSA). The Apnex HGNS™ System, developed by the company, is a device designed to treat OSA, which is a serious, life-threatening illness characterized by fragmented sleep and excessive day-time sleepiness. The HGNS System activates an upper airway muscle during sleep, which opens the airway, allowing patients to breathe and remain asleep. "These results demonstrate the potential benefits the HGNS System could provide to patients who do not tolerate continuous positive airway pressure (CPAP) therapy," said Peter Eastwood, PhD, senior research fellow at the West Australian Sleep Disorders Research Institute of Sir Charles Gairdner Hospital, professor at the School of Anatomy and Human Biology of the University of Western Australia, and an investigator with this study. "In most patients, the Apnex HGNS System reduced the severity of their OSA condition, allowing them to sleep better and feel better." Three- and six-month safety and efficacy data from the study were presented at the American Thoracic Society 2010 International Conference. The findings show the HGNS System reduced the severity of OSA by an average of more than 50 percent, as measured by the apnea-hypopnea index (AHI). AHI measures the number of times per hour during sleep that a person either stops breathing or has restricted breathing. Patients also experienced significant improvements in symptoms, as measured by multiple quality of life surveys. Patients tolerated the treatment well, with an average of 6.5 hours of use each night. There were no device failures during the study. Source: PRNewswire 5/17/10

Phase III Study in Primary Liver Cancer Recommended for Continuation

Celsion Corp. announced in May that after reviewing data from 294 patients, including 12 from Japan, enrolled in the pivotal Phase III ThermoDox® clinical study (HEAT) for primary liver cancer, the data monitoring committee has recommended that the company continue to enroll patients in the trial. "We are pleased that the [committee] has recommended continuation of the study based on its review of all of the available study data," stated Michael H. Tardugno, president and CEO of Celsion. "The [committee's] affirmative review of the 12 Japanese patients enrolled to date is a positive step forward, as it confirms Celsion and Yakult's decision to initiate Phase III trials in Japan. The arrangement to move directly into Phase III trials was based on previous evidence in primary liver cancer patients, [and] may have shortened our timeline for approval in Japan by two years. With recent acceleration in patient recruitment, and the study now almost 60 percent enrolled, we are optimistic of a timely completion to enrollment." The company plans to enroll 600 patients under a Food and Drug Administration Special Protocol Assessment. The study is designed to evaluate the efficacy of ThermoDox in combination with radiofrequency ablation (RFA) when compared to patients who receive RFA alone as the control. The primary endpoint for the study is progression-free survival. Source: PRNewswire 5/13/10

Company to Simultaneously Evaluate Self-Expanding Stent System in U.S. and Japan

Terumo Medical Corp. in May announced it has received an investigational device exemption conditional approval from the U.S. Food & Drug Administration (FDA) for its Occlusive/Stenotic Peripheral Artery Revascularization Study (OSPREY) in the U.S., which will evaluate the safety and effectiveness of the Misago™ self-expanding stent system for use in the superficial femoral artery (SFA). This marks the company's first U.S. clinical trial for a premarket approval device. A unique feature of the clinical trial is that it will simultaneously enroll patients in the U.S. and Japan. Referred to as "Medical Device Collaborative Consultation and Review of Premarketing Applications" under the larger "Harmonization by Doing" (HBD) initiative, Terumo's trial was selected as one of two projects to pilot this approach, which is intended to shorten the gap between product approvals in these two significant world healthcare markets. HBD is an international effort to develop global clinical trials and address regulatory barriers that may be impediments to timely device approvals. This process is a cooperative effort to move both Japan and the U.S. toward international regulatory harmonization. The HBD initiative is a pilot project launched in December 2003 that seeks regulatory convergence between FDA and MHLW-PMDA (Japan's regulatory bodies). The learning obtained in the "proof of concept" trials will assist both regulatory bodies in streamlining the clinical trial process for faster approvals in both countries, as well as promote the idea of global trials for purposes of collecting better data. In this pilot HBD approach, the products will be submitted for review and approval at the same time. In the U.S., OSPREY is a single-arm, multicenter, nonrandomized prospective clinical trial for the treatment of atherosclerotic stenoses and occlusions of the SFA. In Japan, there are two arms of the study, with 50 patients receiving the Misago stent and 50 patients receiving percutaneous transluminal angioplasty. The study will include up to 350 patients, with a maximum of 250 patients in up to 30 centers in the U.S. and 100 patients in Japan. There have already been six patients enrolled in Japan, which received regulatory approval to begin the trial last year. The first U.S. enrollments are expected in June 2010. The Misago stent consists of a nitinol stent pre-mounted on the distal portion of a rapid-exchange delivery catheter system. The stent has three radiopaque markers located on each end of the stent to help ensure accurate placement in the lesion. The stent is currently available for sale in Europe. Source: EurekAlert! 5/12/10

Phase III Registration Program Initiated for Hyperphosphatemia Treatment

Keryx Biopharmaceuticals, Inc. announced in May the initiation of its short-term Phase III study of Zerenex™ (ferric citrate), the company's iron-based phosphate binder for the treatment of elevated serum phosphorous levels, or hyperphosphatemia, in patients with end-stage renal disease on dialysis. The initiation of this study marks the commencement of the company's Phase III registration program for Zerenex, which is being conducted in accordance with a Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration. Pursuant to the company's SPA agreement, the registration program will consist of the short-term efficacy study initiated this month, and a 58-week long-term safety and efficacy study, to be initiated in the third quarter of 2010. Patients completing the short-term study are eligible to be enrolled into the long-term study. The short-term efficacy study is a multicenter, randomized, open-label clinical trial with a planned enrollment of approximately 150 patients on hemodialysis. All patients will undergo a two-week washout period, following which the patients will be randomized 1:1:1 to receive a fixed dose of Zerenex (1 gram, 6 grams, or 8 grams per day) for a treatment period of 28 days. The primary endpoint of the study is to demonstrate a dose response in the change of serum phosphorous from baseline (end of washout period) to end of the treatment period (day 28). Approximately 15 sites in the U.S. will participate in the study. Patient enrollment is expected to take up to six months, with study completion expected by the end of 2010. The long-term safety and efficacy study will be a multicenter, randomized, open-label, safety and efficacy clinical trial with a planned enrollment of approximately 300 patients on hemodialysis or peritoneal dialysis. The long-term study will consist of a two-week washout period followed by a 52-week safety assessment in which patients will be randomized 2:1 to receive either Zerenex or another phosphate binder. The 52-week safety assessment will be followed by a four-week efficacy assessment in which only patients randomized to treatment with Zerenex during the safety assessment will be randomized to continue treatment with either Zerenex or placebo. Keryx expects to complete the Zerenex Phase III program and file a New Drug Application for Zerenex for the treatment of hyperphosphatemia in the first half of 2012. Source: PRNewswire 5/6/10 

International Study Targets Lymphoma, Leukemia

Scott & White's Cancer Research Institute in Central Texas is participating in an international study that targets adult relapsed or refractory B-cell non-Hodgkin's lymphoma and chronic lymphocytic leukemia. The Phase I/II study is open to eligible patients with previously treated B-cell non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia, to include small lymphocytic lymphoma. The clinical trial will evaluate the safety, tolerability, and efficacy of an investigative therapeutic research agent called CAT-8015. This research will ultimately include 30 sites in the U.S., Canada, and Europe, and from 110 to 140 subjects. The study will last about 30 months. Source: EurekAlert! 5/5/10 

Top-Line Study Results Demonstrate Surgical Adhesive's Safety and Preliminary Effectiveness

Cohera Medical, Inc. in May announced that top-line clinical study results demonstrate the safety and preliminary effectiveness of the company's lead surgical adhesive product, TissuGlu®. The prospective, open-label, randomized study involving 40 patients at three sites in Germany met its primary endpoints of safety and preliminary effectiveness related to time to drain removal and secondary endpoints of associated wound healing complications, cumulative wound drainage, number of additional procedures and visits, and improved quality of life. In the trial, investigators compared standard wound closure techniques used in abdominoplasty surgeries, or "tummy tuck," to standard wound closure techniques plus the application of TissuGlu. The purpose of the study was to determine TissuGlu's effect on wound drainage and associated complications in the surgeries. The positive results from the first-in-human study of Cohera's surgical adhesive in abdominoplasty procedures move the product toward CE Mark application in Europe and a larger clinical study in the U.S. this year. The company envisions the TissuGlu market opportunity in plastic surgery to encompass applications beyond tummy tuck, such as breast reconstruction and body contouring. Currently, patients who undergo abdominoplasty require the insertion of drains to remove fluids that accumulate under the skin at the surgical site. In some cases, drainage is inadequate, and the excess fluid accumulation called seroma requires an additional procedure for removal. TissuGlu adheres the tissue flaps created during the procedure to reduce fluid accumulation, and, ultimately, the duration of use of the surgical drains. With the use of TissuGlu, patients may experience a significant reduction of fluid accumulation and a more comfortable recovery, which may lead to a quicker return to normal activity. Source: PRNewswire 5/5/10 

Company to Begin Phase II Trials in Glaucoma in Mid-2010

Inotek Pharmaceuticals Corp. in May presented results confirming the mechanism of action of the company's lead glaucoma candidate, INO-8875, as a trabecular meshwork outflow enhancer. Studies were conducted in human trabecular meshwork cells and multiple preclinical models. INO-8875 has successfully completed a single-dose Phase I/II trial in glaucoma, and is expected to enter Phase II trials with an eye-drop formulation in mid-2010. The data were presented in a poster presentation at the Association for Research in Vision and Ophthalmology Annual Meeting in Fort Lauderdale, Fla. INO-8875 in an eye-drop formulation dose-dependently lowered intraocular pressure (IOP) by 20 to 25 percent from baseline at one to two hours after single doses in normotensive eyes. The IOP-lowering effect of INO-8875 was sustained for four to six hours post-dose. By delivering the drug directly to the tissue of the trabecular meshwork, INO-8875 is able to increase outflow there, while keeping systemic exposure to the drug low. Based on these findings and the positive results from the single-dose clinical trial of INO-8875 in glaucoma, the company plans to initiate its first multiple-dose Phase II clinical trial of INO-8875 in glaucoma in mid-2010. Source: Marketwire 5/4/10 

Phase II Study of Oral Therapy for Gaucher Disease Yields Positive Results

Gaucher disease, a rare enzyme deficiency disorder, is one of many conditions with few approved treatment options for patients. In a study published online in early May in Blood, researchers present positive results of a Phase II clinical trial of eliglustat tartrate, an oral therapy in development to treat Gaucher disease. Gaucher disease is a genetic disorder that occurs when a mutation of the glucocerebrosidase gene causes low activity of that enzyme in the body. As a result, harmful fatty substances accumulate in the liver, spleen, bones, and bone marrow, preventing cells and organs from working properly. The primary treatment option is enzyme replacement therapy, which is given intravenously, to break down the accumulated fatty substances. Eliglustat tartrate is an oral drug currently in development for Gaucher disease type 1 (GD1). As a substrate reduction therapy, the drug decreases the body's production of the fatty substances so they do not accumulate in cells. Based on Phase I trials in healthy volunteers that demonstrated positive initial safety results, the research team initiated a multinational, open-label, single-arm Phase II study of 26 GD1 patients to evaluate the efficacy, safety, and pharmacokinetics of eliglustat tartrate administered orally at 50 mg or 100 mg doses twice daily. Eligible patients had confirmed Gaucher disease, characterized as enzyme deficiency and a spleen volume at least 10 times greater than normal, plus abnormal values of either platelet count or hemoglobin levels. The study endpoint (improvement in at least two of the three main efficacy parameters: spleen volume, hemoglobin level, and platelet count) was met by 77 percent of all patients and 91 percent of the 22 patients who completed the full 52 weeks, with the greatest overall improvements seen in hemoglobin level and spleen volume. The research team found statistically significant improvements across many disease symptoms, including mean hemoglobin level, platelet count, spleen volume, liver volume, and lumbar spine bone mineral density. Furthermore, the patients' glucosylceramide plasma levels normalized. Disease symptoms seemed to respond rapidly, and improvement was seen especially in bone mineral density. This may have resulted from the drug's small molecular size, which allows it to diffuse quickly within affected cells. Further clinical development of eliglustat tartrate is already proceeding with larger, controlled Phase III studies in untreated patients and in patients previously stabilized with imiglucerase--an intravenously administered medication currently used to treat Gaucher disease. Source: EurekAlert! 5/3/10 

On Birth Control Pill's 50th Anniversary, Grant Announced to Study Male Contraceptive

As the birth control pill marks its 50th birthday this month, Los Angeles Biomedical Research Institute (LA BioMed) announced that it has received $1.5 million in grant funding to study a contraceptive for men that uses a combination of two hormonal gels applied to the skin of the arm and abdomen. The Food and Drug Administration approved the birth control pill on May 9, 1960, giving women greater control over their reproductive choices and their lives. Drs. Christina Wang and Ronald Swerdloff are LA BioMed principal investigators and directors of one of only two of the National Institutes of Health centers dedicated to clinical research on male contraceptives. They have conducted several studies of male contraceptives, including the current one. Dr. Swerdloff, the director of the LA BioMed at Harbor-UCLA Medical Center's Male Contraceptive Clinical Trials Center, says the development of a male contraceptive will change men's view of their health and their role in reproductive decisions. "Just as women gained greater control over their reproductive choices and their health with the advent of the birth control pill, a male contraceptive would get men more involved in their personal healthcare and would give them greater reproductive choices," said Dr. Swerdloff. "Men are less likely than women to see their physicians on a regular basis. If they relied on a male contraceptive prescribed by their doctor, men would be more likely to visit their physicians on a regular basis--as women on birth control pills currently do." At LA BioMed, Drs. Wang and Swerdloff are currently enrolling 60 men between the ages of 18 and 50 in a study of a combination of hormonal gels applied to the arm and abdomen to see if they will decrease a man's sperm concentration and count to levels that would make him unable to cause a pregnancy. The research volunteers should not wish to father a child during the course of the study. The study will compare two treatments--combined Nesterone® Gel (a progestin) and Testosterone Gel--to the use of Testosterone Gel alone to suppress sperm production in normal men. The LA BioMed study is supported by National Institutes of Health, National Institute of Child Health and Human Development grants. Source: EurekAlert! 5/3/10 

Trial Compares Spinal Cord Stimulation to Spine Reoperation in Failed Back Surgery Syndrome

Boston Scientific Corp. in May announced the start of patient enrollment in the EVIDENCE study, which compares the therapeutic effectiveness and cost effectiveness of spinal cord stimulation (SCS) therapy to spine reoperation in patients with failed back surgery syndrome (FBSS). The first patient was enrolled by Joseph Buwembo, MD, and Krishna Kumar, MD, FRCSC, at Regina General Hospital in Regina, Saskatchewan, Canada. EVIDENCE is a randomized, controlled trial enrolling 132 patients at 20 sites worldwide. Patients in the SCS arm of the trial will receive the Boston Scientific Precision Plus™ Spinal Cord Stimulator System. The trial will examine treatment response rates (leg pain relief with no request for the alternative therapy) at six and 24 months. Successful patient response is defined as having greater than or equal to 50 percent relief of pain in the lower extremities compared to pain levels prior to the intervention. The Precision Plus Spinal Cord Stimulator System delivers electrical signals that travel along nerve fibers through the spinal cord to the brain. The system masks pain signals by delivering doses of electricity to change pain signals into signals that the brain interprets as a pleasant sensation called paresthesia. Spinal cord stimulation is prescribed for patients with chronic pain in the trunk and/or limbs who have not received adequate relief from physical therapy, pain medications, prior surgeries, or other methods. The system is indicated for use as an aid in the management of chronic pain in the trunk and/or limbs, including unilateral or bilateral pain associated with FBSS and intractable lower back and leg pain. FBSS is defined as persistent or recurrent pain following one or more lumbosacral spine surgical procedures. The pain associated with FBSS is commonly neuropathic and is often described by patients as shooting or burning. SCS is particularly effective in treating neuropathic pain. Source: PRNewswire 5/3/10 

Phase III Lung Cancer Trial Shows Biomarker Identifies Patients Likely to Respond to Drug

Results from the VeriStrat® biomarker analysis of a multicenter Phase III trial were presented in late April at the 2nd European Lung Cancer Conference currently being held in Geneva, Switzerland. Results showed that the VeriStrat test identified patients who were likely to have a survival benefit from treatment with erlotinib, a commonly prescribed oral therapy for advanced non-small cell lung cancer (NSCLC). Following treatment with erlotinib, patients in the group classified as "VeriStrat Good" had a median survival of 10.5 months, compared to 4.0 months in the group classified as "VeriStrat Poor." The study retrospectively applied the VeriStrat proteomic analysis to a subset of the patient population from the NCIC Clinical Trials Group study BR.21, a Phase III, multicenter trial of erlotinib versus placebo in previously treated patients with NSCLC. The VeriStrat analysis involved 441 of 729 patients from the BR.21 study and classified patients as either "VeriStrat Good" or "VeriStrat Poor," based on a proteomic profile. The data suggest that with a VeriStrat Good classification a patient is likely to receive therapeutic benefit from treatment with erlotinib, and with a VeriStrat Poor classification, a patient is likely to derive little therapeutic benefit. VeriStrat Good patients treated with erlotinib had a significant improvement in survival of 10.5 months, compared to 6.6 months on placebo. VeriStrat Poor patients treated with erlotinib had a median survival of 4.0 months compared to 3.1 months on placebo, and showed no statistically significant difference between treatment groups. VeriStrat Good patients also had a significantly higher tumor response rate than VeriStrat Poor patients (11.5 percent versus 1.0 percent). VeriStrat status did not correlate with other biomarkers analyzed in the study. VeriStrat is a pretreatment, serum test for patients with advanced NSCLC. The test identifies patients who are likely to have good or poor outcomes after treatment with epidermal growth factor receptor inhibitors (EGFRIs). Samples are processed in Biodesix' CLIA accredited laboratory and results are typically reported within 72 hours of sample shipment. VeriStrat has been validated in clinical studies in more than 1,000 patients. Biodesix is engaging in additional studies to further validate the test and to explore the clinical utility of VeriStrat in other solid epithelial tumors and with other EGFRIs. Source: PRNewswire 4/30/10 

Company Announces Initiation of Phase III Trial of Onychomycosis Treatment

Celtic Pharmaceutical Holdings L.P. in April announced the enrollment of the first patient into its Phase III trial of TDT 067, terbinafine in Transfersomes®, for the topical treatment of onychomycosis (also known as a fungal nail infection). The three-arm, double-blind study will be conducted in approximately 40 centers around the world, and is powered to provide potentially registrational data on the efficacy, tolerability, and safety of topically applied terbinafine delivered through the Transfersome targeted delivery technology over 48 weeks. PPD Inc., a contract research organization, has been appointed to conduct the study. During Phase II development, TDT 067 achieved two orders of magnitude lower plasma terbinafine concentrations compared to oral terbinafine in a pharmacokinetic study conducted under conditions of maximal use. In contrast, terbinafine levels measured in affected nails were three orders of magnitude higher than those reported for oral terbinafine. This illustrates the targeted delivery of terbinafine. In a Phase II efficacy and safety study, patients treated for only 12 weeks with a primary endpoint of mycological cure at 14 weeks and follow up to 48 weeks, a 90 percent mycological cure rate (as defined by negative culture and negative microscopic examination) was observed at 14 weeks. At 48 weeks, the mycological cure rate was still 38 percent, despite no active treatment for the preceding 36 weeks. TDT 067 was well tolerated with negligible systemic exposure and no serious local side effects, confirming the maximal use study findings, suggesting that patients can be treated for longer durations, which should enable improved efficacy. Source: PRNewswire 4/30/10 

Positive Results Seen from Compound's Use in Chronic Constipation Study

Albireo in April announced that additional clinical data will be reported from a recent study assessing the safety, tolerability, and efficacy of A3309 in patients with chronic constipation. A3309 is a first-in-class investigational compound for the treatment of irritable bowel syndrome with constipation and chronic constipation. The results were presented during the 2010 Digestive Disease Week annual meeting in New Orleans, La. A3309 is currently being evaluated in a large Phase IIb study in chronic constipation enrolling approximately 180 patients in the U.S. and further investigation of A3309's enhancement of large bowel transit is being conducted at the Mayo Clinic. Also, given the mode of action, A3309 may be beneficial in patients with dyslipidemia, and a study to evaluate A3309 in patients with high cholesterol levels is being conducted in Sweden. Results of these clinical studies will be available late this year, and plans are to move forward into Phase III in chronic constipation during 2011. In the recent randomized, double-blind, placebo-controlled, prospective dose-escalating study, 30 patients were administered placebo or A3309 in a dose range of 0.1 mg to 10 mg for 14 days. In addition to evaluating safety and tolerability, bowel habits and gastrointestinal symptoms from patient diaries and radiographic assessments of transit were used to assess the efficacy of A3309. There were no serious adverse events reported and no patient discontinued the trial. Adverse events were evenly distributed across the different dose levels and no difference was observed compared to placebo. The mode of action--inhibition of bile acid reabsorption in the small bowel--was clearly demonstrated by biomarker analysis, and colonic transit was improved in the higher dose groups as was the number of bowel movements. In addition, stool consistency improved. A3309 modulates the reuptake of bile acids by inhibiting the ileal bile acid transporter. This results in an increased concentration of bile acids in the colon, which, in turn, increase fluid secretion and colonic motility. Source: PRNewswire 4/29/10 

Catheter for Varicose Veins Trial Results Announced

Results from the initial clinical trial of the ClariVein® catheter, used in a new minimally invasive treatment for varicose veins, have been announced. The device combines mechanical and chemical modalities to accomplish vein treatment in an in-office setting. Steve Elias, MD, FACS, FACPh, principal investigator of the trial at Englewood Hospital and Medical Center in New Jersey, reported that the initial success rate was equal to that from radiofrequency or laser treatment of great saphenous vein disease. Thirty patients with an average age of 55 were part of the first-in-human trial. Most patients had symptomatic varicose veins, with some having more advanced vein disease, such as swelling and skin changes. Mean vein diameter was 8.1 mm. Treatment for each vein averaged five minutes, and overall procedure time was 14 minutes. At six-month followup, 29 of the 30 veins treated were successfully closed. The only vein that did not respond was that of the first patient. Subsequent to the trial, to date 22 other patients have had the procedure, with all being successful. The ClariVein catheter is a product of Vascular Insights LLC, which has received 510(k) clearance from the U.S. Food and Drug Administration to market ClariVein for infusion of physician-specified agents in the peripheral vasculature. Source: PRNewswire 4/21/10 

Positive Results Seen in Grass Pollen Phase III Trial

Stallergenes S.A. in April announced the first results of a Phase III clinical trial (VO61.08) conducted in the U.S. on its sublingual grass pollen immunotherapy tablet, Oralair®. This study is the first clinical study in the U.S. to be conducted by Stallergenes as part of the product's clinical development, which already encompassed four Phase III clinical trials conducted in Europe. This development program has so far included more than 2,300 patients. This study is pivotal in the perspective of a market authorization application for Oralair in the U.S. with an adult indication. The VO61.08 study is a randomized, double-blind, placebo-controlled trial. It included 473 adult patients, aged 18 to 65 years, suffering from grass pollen-induced rhinoconjunctivitis, in 51 centers. The primary endpoint, the reduction of the "combined score" (taking into account symptoms and rescue drugs) by the drug compared to the placebo, was statistically very significant, and of a similar magnitude to the results of European studies. The Oralair active substance consists of five purified and calibrated pollen extracts corresponding to the epidemiological characteristics of patient exposure in Europe: perennial rye grass (Lolium perenne), meadow grass (Poa pratensis), timothy grass (Phleum pratense), cocksfoot (Dactylis glomerata), and sweet vernal grass (Anthoxanthum odoratum). The treatment is taken for four months prior to the pollen season and then throughout it, for three consecutive seasons, rather than as a perennial protocol. Source: PRNewswire 4/19/10 

First Patient Treated in Percutaneous EVAR Clinical Trial

Endologix, Inc. in April announced that the first patient has been enrolled in the company's prospective, multicenter, randomized clinical trial for a bilateral percutaneous approach to endovascular abdominal aortic aneurysm repair (EVAR). The patient was treated at Oklahoma Heart Hospital by Jim G. Melton, DO. Standard EVAR procedures require an open surgical cut-down of one or both femoral arteries for delivery system access and device deployment. Percutaneous EVAR (PEVAR) procedures do not require an open surgical cut-down of either femoral artery, as access to the femoral artery is achieved via a percutaneous (across the skin) approach. There are currently no medical devices approved by the U.S. Food and Drug Administration, or in pivotal clinical trials, for a PEVAR indication. Up to 20 U.S. clinical sites will enroll 150 patients in the randomized trial. All patients will be treated with the Endologix IntuiTrak® endovascular delivery system, which delivers the company's Powerlink® family of stent grafts. The clinical trial is also utilizing a pre-close technique facilitated by the Abbott Vascular, Inc. Prostar® XL Percutaneous Vascular Surgical System or Perclose ProGlide® Suture-Mediated Closure System. One hundred patients will undergo PEVAR with closure facilitated by either the Prostar XL or Perclose ProGlide device, and 50 patients will undergo standard EVAR. Source: PRNewswire 4/14/10 

Positive Phase II Results Achieved in Study of Therapy for Primary Biliary Cirrhosis

Intercept Pharmaceuticals, Inc. in April announced results from its recently completed Phase II clinical trial of INT-747 (obeticholic acid) in patients with primary biliary cirrhosis (PBC) during the 45th Annual Meeting of the European Association for the Study of the Liver. This double-blind, placebo-controlled, dose-response study evaluated INT-747's ability to lower serum alkaline phosphatase (AP) after 12 weeks of treatment in patients with an inadequate response to ursodeoxycholic acid (UDCA) treatment. AP is a validated marker of PBC disease progression and clinical outcome that is routinely used to evaluate the status of PBC patients and response to therapy. The study assessed the efficacy of INT-747 added to ongoing UDCA therapy in patients with AP values greater than or equal to 1.5 times the upper limit of normal (ULN = 117 U/L). Other liver enzymes, such as gamma glutamyl transferase (GGT) and alanine aminotransferase (ALT)--general indicators of liver injury and function--were also measured. The study was conducted at more than 30 centers in eight countries across North America and Europe, the largest PBC study group assembled to date. In total, 165 patients were randomized to one of three doses of INT-747 (10 mg, 25 mg, or 50 mg) or placebo taken once daily for 12 weeks with a two-week followup. All three doses of INT-747 significantly lowered AP by 21-24.7 percent, with absolute values decreasing by 66-77 U/L, compared to a 2.6 percent (5 U/L) reduction in the placebo group. INT-747 reduced GGT by 48-63 percent in the three treatment groups, compared to a 7 percent increase in the placebo group; similarly, ALT was reduced by 21-35 percent in the treatment groups, with no change for placebo. In summary, the 10 mg lowest dose of INT-747 showed good efficacy and was well tolerated. Intercept is planning for an end of Phase II meeting with the Food and Drug Administration, with the goal of initiating a Phase III program in PBC thereafter.Source: PRNewswire 4/13/10 

New Phase II Study Supports Potential of Steatohepatitis Treatment

Results from a multinational Phase II study presented in April at the International Liver Congress 2010 have shown that treatment with the caspase inhibitor GS-9450 can reduce markers of liver damage in patients with nonalcoholic steatohepatitis (NASH--the most serious form of nonalcoholic liver disease), as demonstrated by reduced levels of alanine (ALT) and aspartate aminotransferases (AST), hepatic enzymes that indicate cell damage. GS-9450, a potent inhibitor of caspases-8, -9 and -1, the intracellular proteins that initiate programmed cell death (or cell suicide, also known as apoptosis) in damaged cells, is a potential new treatment option for patients with NASH--a disease characterized by fat build-up in liver cells with subsequent inflammation resulting in accumulation of scar tissue (fibrosis), cirrhosis, and eventual liver failure. In this double-blind, parallel-group study, patients (n=124, principally male, mean age 45 years, with Body Mass Index greater than 30 kg/m2) with biopsy-proven NASH were randomized to receive 1, 5, 10, or 40mg GS-9450 or placebo once daily for four weeks. After four weeks on treatment, patients in the 40 mg treatment group experienced the greatest reduction in ALT and AST levels. At week four, linear regression of ALT versus GS-9450 dose was highly significant, with 35 percent achieving ALT levels within the normal range (7-56 U/L), compared to none at study baseline, and 48 percent achieving normal levels of AST (5-40 U/L1), compared to 20 percent at baseline. Placebo treatment showed no meaningful change for ALT or AST. Additionally, the on-treatment measure of cytokeratin-18 caspase cleavage fragments (proteins that act as markers for liver cell death) declined in the 10 and 40 mg dose groups (median baseline and week four values respectively were 540 and 445 U/L in the 10 mg group and 562 and 386 U/L in the 40 mg group), although no dose-related response was seen. Source: EurekAlert! 4/16/10 

First-in-Class Drug Tested in Patients with Advanced Cancer

Researchers at Boston Biomedical, Inc., are working to develop a novel first-in-class cancer drug that works by targeting the stem-like properties of some cancer cells, and so far, results of an ongoing Phase I clinical trial demonstrate early signs of a strong safety profile and clinical activity. "Cancer stem cells arguably represent one of the hottest frontiers in cancer research today," said Chiang J. Li, MD, chairman and chief executive officer of Boston Biomedical, Inc., who led the research discovery. "If the cancer stem cell hypothesis is proven to be correct, it should be possible to fundamentally advance treatment for patients with a wide variety of cancers because these highly malignant cell populations are inherently resistant to conventional therapies." Updated data were presented during the late-breaking clinical trial symposium at the AACR 101st Annual Meeting 2010 in April. Li and colleagues took an unconventional line of attack by developing BBI608, a first-in-class cancer cell stemness inhibitor that can target highly malignant cancer stem cells, as well as other heterogenous cancer cells. "Current debates or controversies regarding the cancer stem cell hypothesis are less relevant to our approach, since we believe it is crucial to target all malignant cells," said Li. The Phase I study of BBI608 was designed to determine its safety and to establish a dose regimen for Phase II trials in adult patients with various advanced cancers. The study is being conducted at the Segal Cancer Center, Montreal, Quebec, Canada; the Juravinski Cancer Center, Hamilton, Ontario, Canada; and the Karmanos Cancer Center, Detroit, Mich. As of March 26, 18 cancer patients with various solid tumors were enrolled in the study. Treatment with BBI608 consisted of twice-daily, oral administration for four-week cycles. Dose escalation of BBI608 has reached a daily regimen of 600 mg, and the blood concentration of BBI608 has exceeded the level required to kill cancer stem cells and heterogeneous cancer cells in the laboratory. To date, nine patients were evaluated for antitumor activity, of which six have achieved stable disease for at least two months, with early signs of tumor regression and prolonged stable disease. Source: EurekAlert! 4/19/10 

Investigator-Sponsored Trial Program Launched for Cancer Treatments

Peregrine Pharmaceuticals, Inc. in April announced the launch of an investigator-sponsored trial (IST) program for bavituximab and Cotara®. Bavituximab is a novel approach to treating cancer and viral infections and has demonstrated promising interim results in ongoing Phase II clinical trials in non-small cell lung cancer (NSCLC) and advanced breast cancer. Cotara is a brain cancer therapy currently in a Phase II clinical trial for recurrent glioblastoma multiforme, and has generated promising survival data in earlier studies. "Even before formally announcing our IST program, we have been receiving an increasing number of requests from investigators interested in conducting clinical studies with either bavituximab or Cotara, and we are eager to evaluate proposals and begin working with investigators to start new clinical studies," commented Marvin R. Garovoy, MD, head of clinical science at Peregrine. "The launch of our new IST program comes as we prepare to present additional data from multiple clinical studies at upcoming conferences and provide updates to the oncology community. We believe our IST program can provide valuable information on mechanisms of action, use in additional oncology indications, and application in different therapeutic combinations, and we welcome the opportunity to offer this program to oncologists who share our excitement over the clinical potential of our novel agents." This program offers oncologists the opportunity to conduct clinical trials for Cotara in brain cancer and for bavituximab in breast cancer, fibrosarcoma, brain cancer, Hodgkin's lymphoma, NSCLC, pancreatic cancer, prostate cancer, colorectal cancer, melanoma, renal cancer, urinary bladder cancer, hepatocellular carcinoma, and ovarian cancer. Source: Marketwire 4/12/10

First Patients Enrolled in Trial of New Stent Graft System to Treat Abdominal Aortic Aneurysm

Cordis Corp. announced in April that the first patients have been enrolled in the INNOVATION trial, which will assess the safety and performance of a new stent graft system, called INCRAFT™, to treat abdominal aortic aneurysm (AAA). The multicenter, open-label, prospective, nonrandomized study will enroll up to 25 patients in three sites throughout Germany. According to the researchers, current stent grafts have large and bulky delivery systems, making device introduction impossible for small or diseased access vessels. It is hoped that the ultralow profile delivery system of INCRAFT will make endovascular aneurysm repair a possible treatment alternative for a wider range of patients. Cordis has been developing INCRAFT with input from a multidisciplinary physician advisory panel that includes Takao Ohki, MD, chairman of the Department of Surgery at Jikei University School of Medicine in Tokyo; Corey Teigen, MD, managing physician partner at MeritCare Vascular Center, Fargo, N.D.; and Robert Bersin, MD, medical director for endovascular services at Seattle Cardiology and Swedish Medical Center, Wash. The trial is sponsored by Cordis, and its investigators and sites are under contract with Cordis to perform this research. Source: PRNewswire 4/9/10

Intranasal Product Aims to Treat Migraines

OptiNose in April announced the publication in Cephalalgia of results from its Phase II clinical study investigating the efficacy and tolerability of its novel, intranasal drug/device product for the treatment of migraine. Sumatriptan powder in 10 mg and 20 mg doses administered intranasally using OptiNose's bidirectional delivery device was highly effective in treating a single attack of moderate or severe migraine. The proportion of patients pain-free at two hours was 54 percent for the 10 mg dose, 57 percent for 20 mg, and 25 percent for placebo. These results compare very favorably with published figures of 26-42 percent for liquid sumatriptan nasal spray and 35.6 percent for zolmitriptan nasal spray, and higher than the 28 percent/29 percent reported for oral triptans. In addition to high efficacy, OptiNose's bidirectional powder delivery eliminates drip-out and reduces the bitter taste associated with conventional nasal triptan products. The onset of pain relief was much quicker than conventional orally and nasally delivered triptans, and similar to subcutaneous injection of sumatriptan, despite much lower systemic exposure. Sustained pain-freedom at 48 hours was also high for both doses. Treatment-related adverse events were rare. OptiNose's breath-actuated devices deliver intranasal drugs to targeted regions in the nasal cavity, including the sinus openings and the olfactory region. This is achieved without any risk of lung deposition, unlike traditional nasal inhalers, nasal sprays, or nebulizers. The company offers both single and multiuse intranasal delivery devices for liquid and powder formulations. The technology has been successfully tested in a number of clinical trials to date, including gamma scintigraphy studies to confirm highly superior deposition, studies evaluating the immune response to conventional antigens, trials showing excellent effects in chronic sinusitis with and without nasl polyps, and studies evaluating the delivery of CNS active compounds. Source: EurekAlert! 4/7/10

Company Announces Completion of Enrollment Platelet Reactivity Measurement Study

Accumetrics, Inc., developer and marketer of the VerifyNow System for measuring platelet reactivity to multiple antiplatelet agents, announced that it has completed the enrollment phase of its landmark clinical trial, GRAVITAS (Gauging Responsiveness with A VerifyNow assay Impact on Thrombosis And Safety). The trial is specifically designed to demonstrate the value of providing clinicians with actionable information for patients who are poor responders to clopidogrel (Plavix). The multicenter, placebo-controlled trial will determine whether tailored antiplatelet therapy for poor responders, identified based on the results of the company's VerifyNow P2Y12 Test, reduces major adverse cardiovascular events (e.g., heart attack, stent thrombosis) following percutaneous coronary intervention (PCI). The trial is being conducted at approximately 80 sites in the U.S. and Canada, and has enrolled approximately 2,800 patients. The concept of variability in response to antiplatelet therapy has been well established. Also being demonstrated with increased frequency is the relationship between poor response to antiplatelet therapy and poor patient outcomes. The GRAVITAS trial is the first study of its kind to determine whether tailored antiplatelet therapy, based on the results of Accumetrics' VerifyNow System and P2Y12 Test, reduces major adverse cardiovascular events post-PCI. The trial is being coordinated by Scripps Advanced Clinical Trials. Source: PRNewsire 4/6/10

Lithium Trial Fails to Replicate Initial Success for ALS

Contrary to promising results from a recent small pilot study that generated a high level of off-label use, lithium does not delay disease progression in patients with amyotrophic lateral sclerosis (ALS), also known as motor neuron disease or Lou Gehrig's disease, according to the first double-blind, randomized trial of the drug. As such, lithium should not be used as a treatment in patients with ALS, concludes an article published online first and in the May edition of The Lancet Neurology. Since the licensing of riluzole (which has been shown to extend the lives of patients with ALS by an average of three months) 15 years ago, no new drug has been approved for the treatment of ALS, and there is currently no therapy that can cure ALS. However, in 2008, a small pilot study reported that daily doses of the drug lithium, traditionally used in the treatment of bipolar affective disorder, might dramatically slow down progression of ALS. Results showed that after 15 months, there were no deaths in the 16 patients treated with lithium plus riluzole, but 30 percent of those taking riluzole alone died. Additionally, patients taking lithium had a slower decline in disease-related disability. To date, no other treatment has shown such a dramatic effect on ALS. However, the study involved a small number of patients, and the participants were not blinded to treatment, so definite conclusions about the effectiveness of lithium could not be made. To further investigate the potential of lithium as a possible treatment for ALS, a team of researchers from the Northeast and Canadian ALS Consortia led by Swati Aggarwal from Massachusetts General Hospital and Lorne Zinman from Sunnybrook Health Sciences Center designed a novel, double-blind, placebo-controlled, time-to-event trial. Initially, 84 patients with ALS from across the U.S. and Canada were randomly assigned to receive lithium plus riluzole (40) or placebo plus riluzole (44) in similar doses to the pilot study. Several reviews of the data were planned, the first after the 84th person was enrolled, when a decision was to be made on whether to expand the trial to include 250 patients. The primary outcome measure was time to an event, defined as a decrease in ALS functional rating scale-revised (ALSFRS-R) score by at least six points or death. A log-rank statistical test was done at the initial interim analysis to compare the distributions of the time to an event between the lithium and placebo groups. The trial was stopped after the first interim analysis, as the evidence suggested that a large effect of lithium would not be seen as demonstrated in the earlier pilot study. Source: EurekAlert! 4/5/10

Enrollment Begins for Phase I Regenerative Trial in Heart Failure

Juventas Therapeutics in April announced it has started enrolling patients in a Phase I clinical trial for JVS-100 to evaluate safety and efficacy in the treatment of patients with Class III heart failure. JVS-100 encodes Stromal Cell-derived Factor-1 (SDF-1) and has been shown in preclinical studies to significantly increase cardiac function by promoting cell survival and increasing new blood vessel formation in the damaged organ. Specifically, the company completed studies in heart failure pig models demonstrating that JVS-100 treated pigs showed statistically significant improvements in key indicators of cardiac function and remodeling, including reductions in left ventricular end systolic volume. According to the company, the initiation of this trial builds upon years of work in its laboratory demonstrating that SDF-1 is a key molecular factor that attempts to repair damaged tissue through the local recruitment of stem cells. In humans, natural SDF-1 expression is too short-lived to provide any benefit; however, by delivering JVS-100, the company hopes to prolong SDF-1 expression, or reintroduce it, at a time remote from injury for a period of time sufficient to promote significant tissue repair. The company says that JVS-100 has the potential to provide therapeutic benefits associated with regenerative medicine without the complexity of having to deliver stem cells to the patient. Source: PRNewswire 4/5/10

Phase II Data Show Multiple Clinical Benefits in Patients Undergoing Arthroscopic Meniscectomy Surgery

Omeros Corp. in late March announced that a Phase II clinical trial of OMS103HP, its product candidate for arthroscopy, demonstrated that patients treated with OMS103HP during arthroscopic knee meniscectomy surgery achieved statistically significant clinical benefits. OMS103HP is an investigational drug product that is added to arthroscopic irrigation solution and is designed to improve postoperative joint function and motion and reduce postoperative pain. The trial was a multicenter, randomized, double-blind, vehicle-controlled study. Of the 161 patients who were enrolled and treated, 143 patients met the predetermined surgical criteria and were included in the data analysis (71 OMS103HP and 72 vehicle). There were no important differences in demographic characteristics between the two treatment groups. This study has shown that OMS103HP provides greater efficacy than vehicle as measured by visual analog scale (VAS) pain scores, passive knee flexion, and patient-reported functional scores using the Knee Injury and Osteoarthritis Outcome Score (KOOS). The patient-reported outcomes showed a sustained benefit through postoperative Day 90. OMS103HP was well tolerated, and adverse events were more frequent in the vehicle dose group. Pain scores in the immediate 24-hour period, and up to seven days postoperatively, were measured using a validated, 100-point VAS. Range of motion assessments were made at baseline and day seven postoperatively. The protocol was amended to collect patient self-reports using the KOOS, which consists of five subscale scores: symptoms, pain, activities of daily living, sport and recreation function, and knee-based quality of life. The KOOS subset consisted of 67 subjects (33 OMS103HP and 34 vehicle). OMS103HP is injected into standard arthroscopic irrigation solutions and perfused through the joint in low concentrations during surgery. It is currently being evaluated in a Phase III clinical program for anterior cruciate ligament surgery. If approved, OMS103HP would be the first commercially available drug delivered directly to the surgical site to improve function following arthroscopic surgery. Source: PRNewswire 3/31/10

Treatment for Acute Angioedema in Pediatric Patients Enters Phase II

ViroPharma Inc. in late March announced that it has initiated an open-label, single-dose, Phase II study to evaluate doses of Cinryze™ (C1 esterase inhibitor [human)] for treatment of acute angioedema attacks in children less than 12 years of age with hereditary angioedema (HAE). Cinryze was approved by the U.S. Food and Drug Administration in October 2008 for routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE. Cinryze is not approved in the U.S. for acute treatment of attacks or in pediatric patients below the age of 12 years. The study design was agreed upon with the Pediatric Committee of the European Medicines Agency as a component of the Pediatric Investigational Plan that was approved prior to the company's recent submission of a Marketing Authorization Application for Cinryze. The objectives of the study are to evaluate the dose response and the pharmacokinetics/pharmacodynamics of IV administration of Cinryze; and to determine the safety and tolerability following IV administration of Cinryze in the study population. The multicenter, open-label study will be conducted in 12 pediatric patients. Eligible subjects (2 years to less than 12 years of age) will receive treatment for a single acute HAE attack. Cinryze will be administered as a single IV infusion of 500 U, or 1,000 U (for subjects 10-25 kg) and 1,000 or 1,500 U (for subjects greater than 25 kg). Patients will be evaluated for HAE symptom relief and will have blood samples collected for complement levels including antigenic and functional C1 INH and C4. The primary efficacy assessment will be made based on clinical response observed within four hours after dosing. Source: PRNewswire 3/31/10

Company Discontinues Phase III Trial of Pancreatic Cancer Treatment

GenVec, Inc. announced in late March that it is discontinuing its Phase III clinical trial of TNFerade™ in patients with locally advanced pancreatic cancer, based on results of an interim analysis. This interim analysis of overall survival, conducted after the 184th death (two-thirds of total expected events), was designed to determine whether the study should continue. GenVec has determined, after conferring with its independent data safety monitoring board, that the PACT trial would not meet the goal of demonstrating persuasive evidence of clinical effectiveness that could form the basis for regulatory approval in the population chosen for study. This randomized, controlled trial compared treatment with TNFerade (in combination with standard of care [SOC]) to SOC alone in patients with locally advanced pancreatic cancer. These interim data demonstrated an approximately 8 percent lower risk of death in the TNFerade plus SOC arm relative to the SOC alone. Accordingly, these data strongly suggest the trial will not achieve the statistical significance required to form the basis for approval of a biological license application in the population chosen for study, thereby warranting discontinuing the trial. The company is in the process of notifying the investigators and regulatory agencies of the discontinuation of the PACT trial. "We are disappointed that the PACT trial did not provide sufficient evidence of the clinical effectiveness of TNFerade to warrant completion of the trial," said Mark Thornton, MD, PhD, senior vice president of product development at GenVec. "We will, of course, continue to follow the patients currently enrolled in the trial, and are conducting additional analyses of the data from the trial and expect that the results will be presented in the future at an appropriate scientific meeting." Added Paul H. Fischer, PhD, president and chief executive officer at GenVec, "We acknowledge and thank the patients and investigators who participated in this trial. ...[I]n addition to TNFerade, our research and development pipeline consists of a number of funded vaccine programs.... At this time, we will continue to focus on those programs and supporting our collaboration with Novartis to develop treatments for hearing loss." GenVec's PACT trial was a multicenter, randomized, active, and controlled study of 330 patients. Source: PRNewswire 3/29/10

First Independent Trial Validates Real-World Performance of Test to Detect HPV Types

Hologic, Inc. in late March announced that interim data from the first large-scale independent evaluation of clinical performance of Cervista® HPV HR compared to Hybrid Capture 2 (hc2), were presented at the 4th Biennial Meeting of AOGIN (Asia-Oceanic Research Organization in Genital Infection and Neoplasia) in New Delhi, India, in March. Cervista HPV HR is a diagnostic test for the detection of 14 high-risk human papillomavirus (HPV) types. The study, SHENCCAST II, is a major cervical cancer screening trial including more than 10,000 women that is being conducted in China to evaluate the performance of HPV assays, among other endpoints. A preliminary analysis of data from 5,043 patients showed the Cervista HPV HR test performed as follows: Overall HPV positivity for this cohort was 12.2 percent for the Cervista HPV HR test and 14.6 percent with the hc2 test. For histologically confirmed CIN 2 or more severe lesions, the Cervista HPV HR test showed a sensitivity of 90.7 percent and a specificity of 90.2 percent. For the hc2 test, sensitivity and specificity were 94.7 percent and 87.9 percent, respectively. While the Cervista HPV HR test demonstrated improved specificity and the hc2 test yielded higher sensitivity, a statistical analysis of overall test accuracy that plots sensitivity and specificity found the two methods were clinically equivalent. Approved by the U.S. Food and Drug Administration in March 2009, Cervista is the first new HPV assay in more than a decade. Source: PRNewswire 3/29/10

Phase III Trial in Lung Cancer Halted Following Interim Analysis

Antisoma plc announced in late March that the planned interim analysis of data from the ATTRACT-1 Phase III trial of ASA404 in previously untreated non-small cell lung cancer has shown that continuation of the trial would be futile, as there is little or no prospect of demonstrating a survival benefit with ASA404 in this setting. The ATTRACT-1 trial will therefore be halted. No new or unexpected serious adverse effects of ASA404 have been identified by the trial's data monitoring committee. Glyn Edwards, CEO of Antisoma, said: "We are disappointed by the outcome of the ATTRACT-1 study, especially given the very encouraging Phase II data reported in the same setting. We had hoped that this trial would show that use of ASA404 could improve treatment for patients with newly diagnosed lung cancer. We are now focused on delivering Phase III results for our other late-stage product, AS1413." Source: Marketwire 3/29/10

Trial for Diabetic Macular Edema Enrolling Patients

A Phase II clinical trial for a promising treatment for diabetic eye disease has begun enrolling participants. The Juvenile Diabetes Research Foundation and the Wilmer Eye Institute of Johns Hopkins University announced in March that the READ 3 Study (Ranibizumab for Edema of the mAcula in Diabetes--Protocol 3 with High Dose Study), with funding from Genentech, Inc., will evaluate the safety and efficacy of a injections of an antibody treatment in people with diabetic macular edema (DME), a major complication of diabetes and a leading cause of blindness in adults. The study involves 14 clinical centers across the U.S. that will collectively enroll some 100 patients and compare two different doses of the antibody treatment to determine if a higher dose is more effective in improving vision and decreasing retinal thickness; it will also determine if higher doses can reduce the frequency of subsequent treatments for DME. Participants will receive either one or two doses of ranibizumab for six months, followed by a six-month follow-up period with the option for additional treatments. Ranibizumab is an antibody designed to block a protein called vascular endothelial growth factor (VEGF), which is produced in excessive amounts in people with diabetes. VEGF causes leakage in the small blood vessels of the eye that can lead to vision loss and, eventually, blindness. In addition to the READ studies, Genentech is conducting two parallel Phase III trials studying the safety and efficacy of different doses of ranibizumab to treat DME. Source: EurekAlert! 3/26/10

Phase I Initiated for Narcolepsy and Cataplexy Treatment

Arena Pharmaceuticals, Inc. announced in March the initiation of patient screening in a Phase I clinical trial of APD916, a novel oral drug candidate for the treatment of narcolepsy and cataplexy. The randomized, double-blind, placebo-controlled trial is planned to enroll up to 72 healthy adult volunteers, and will evaluate the safety, tolerability, and pharmacokinetics of single-ascending doses of APD916, an inverse agonist of the histamine H3 receptor. The histamine H3 receptor is predominantly expressed in the brain, and inverse agonists of the H3 receptor increase the synthesis and release of histamine through inhibition of presynaptic autoreceptors. Enhanced histamine release plays an important role in arousal, and the histaminergic system is at least partly under the control of orexin/hypocretin neurons. Narcolepsy with and without cataplexy have been associated with orexin/hypocretin deficiency and low levels of histamine in cerebrospinal fluid. Therefore, an H3 inverse agonist, by increasing central histamine activity, could be effective in the treatment of these conditions. APD916 was efficacious in multiple preclinical models, and the data suggest APD916 has potential utility in the treatment of narcolepsy with or without cataplexy. Source: PRNewswire 3/24/10

New Drug for Menstrual Cramps Shows Early Promise

Scientists in March described the discovery of a new drug, VA111913, which is currently in Phase II clinical trials, designed to specifically target the root cause of painful menstrual cramps, not just the symptoms. The condition, called dysmenorrhea, is the leading cause of absenteeism from school and work among women in their teens and 20s. The scientists described the study at the American Chemical Society 239th National Meeting. Vantia Ltd, a pharmaceutical company in the United Kingdom, is developing and testing the drug to block the hormone vasopressin, which plays a role in regulating contraction of the uterus. The drug is administered orally, as a pill, rather than in an injection. Last year, VA111913 successfully passed a landmark toward becoming a new drug, when the first stage of clinical trials showed that it was safe for further clinical studies, with no apparent ill-effects. The next phase of clinical trials is currently under way in the U.K. and the U.S. (at sites in Peoria, Ariz.; Austin, Texas; and Salt Lake City, Utah) to evaluate how well it works to control pain in a group of women with dysmenorrhea. Investigators expect results to be available later this year. If studies continue to show promise, the drug could be available to patients in four years, the scientists say. Source: EurekAlert! 3/23/10

First Patient Treated in Trial for Improvement in Scar Appearance

Garnet BioTherapeutics, Inc. in March announced that the first patient has been treated in a Phase II multicenter, double-blind, placebo-controlled study of its lead product candidate GBT009 at Unity Hospital in Rochester, N.Y. GBT009 gives off a variety of pro-regenerative growth factors and cytokines to help repair damaged tissue and reduce inflammation. The trial will assess the safety and efficacy of GBT009 for the treatment of incisional wounds following breast reconstruction surgery. The transverse rectus abdominis myocutaneous (TRAM) flap is a common type of breast reconstruction that uses skin, muscle tissue, and fat tissue from the lower abdomen to create a very natural looking breast. Breast reconstruction with TRAM flap surgery is a major, invasive procedure, and carries with it the possibility of significant complications, including poor wound healing. The GBT009 clinical trial targets female patients scheduled for a mastectomy with breast reconstruction surgery using an abdominal flap technique. The goal of this study is to assess whether intradermal injections of GBT009 along full thickness abdominal incisions following surgery leads to an improvement in scar appearance. Efficacy measures include assessments of scar appearance that will be periodically evaluated by the investigator and patient using several scales. In addition, photographs will be taken throughout the study, and an independent scar assessment panel will evaluate and rate the standardized, calibrated digital photographs. Garnet is initially developing its cell-based therapy for cosmetic and dermatologic applications where accelerated healing and reduced scarring are desirable, but believes that the therapy may also be applicable for treatment of burns, autoimmune disorders such as psoriasis, and in other conditions where inflammation or scar formation plays an important role in disease pathology. Source: PRNewswire 3/23/10

Phase II Opens for Treatment of Type 2 Diabetes Mellitus

ChemoCentryx, Inc. in March announced that it has undertaken a randomized, double-blind, placebo- and active-controlled Phase II clinical trial of CCX140, a novel, orally available small molecule compound designed to specifically target the chemokine receptor known as CCR2. This receptor has been shown to play a role in the inflammatory response associated with metabolic diseases, including Type 2 diabetes, as well as other diseases, including vascular restenosis following stent placement and multiple sclerosis. Chronic inflammation is now thought to be central to the development of insulin resistance in Type 2 diabetes. Macrophages represent as much as 40 percent of the cell population in obese adipose tissue; the majority of these macrophages are derived from CCR2-positive monocytes recruited from the blood. CCX140 is an antagonist of the CCR2 chemokine receptor that works works by blocking the monocyte/macrophage infiltration that occurs during inflammation, and thus is designed to provide selective treatment of the disease without compromising other immune functions. Successful completion of single and multiple ascending dose Phase I studies in healthy volunteers showed that CCX140 was safe and well-tolerated. The study is expected to enroll approximately 140 patients. Eligible patients will be randomized to one of four treatment groupss: placebo once daily; pioglitazone hydrochloride at 30 mg once daily; CCX140 at 5 mg once daily; and CCX140 at 10 mg once daily. Dosing will be for 28 days with a 28-day follow-up period. Source: PRNewswire 3/22/10

Oral Controlled-Release Hydrocodone Heads Into Phase III

Zogenix, Inc. announced that it has initiated a pivotal Phase III clinical trial with ZX002, a novel, oral, controlled-release formulation of hydrocodone without acetaminophen. ZX002 is being developed for the treatment of moderate to severe pain in individuals who require around-the-clock opioid therapy for the control of pain. Hydrocodone is the most widely prescribed drug in the United States, but there are currently no products available with hydrocodone only, or with controlled-release formulations. The U.S.-based multicenter, randomized, double-blind, placebo-controlled trial for ZX002 is designed to enroll approximately 600 patients with chronic low back pain to evaluate efficacy, safety, and tolerability. Source: PRNewswire 3/17/10

Dual Action Drug Shows Promise Against High Blood Pressure and Heart Disease

A new dual-action drug, called LCZ696, is well tolerated and provides significantly greater reductions in blood pressure than the established angiotensin receptor blocker (ARB) valsartan in patients with hypertension (high blood pressure). LCZ696 might be superior to standard ARBs, and has the potential to be a promising treatment for hypertension and heart disease, concludes an article published online first and in a recent edition of The Lancet. The single-molecule LCZ696 is an angiotensin-II-receptor and neprilysin inhibitor (ARNI) that works in two ways. Like ARBs, it blocks the action of angiotensin II, a hormone that causes arteries to constrict (and the drug therefore should allow blood to flow more easily), but it also neutralises a substance called neprilysin, which results in the blood vessels relaxing and widening, thereby lowering blood pressure. It has been suggested that, because the drug blocks both angiotensin II and neprilysin, it has the potential to offer superior benefits for the treatment of hypertension and heart failure compared with ARBs. In this study, Luis Ruilope from Hospital 12 de Octubre, Madrid, Spain and international colleagues examine whether the dual mechanism of action of LCZ696 leads to further lowering of blood pressure compared with the ARB valsartan. A total of 1,328 patients with mild-to-moderate hypertension were recruited from 18 countries and randomly assigned to eight weeks treatment in one of eight groups: 100 mg LCZ696, 200 mg LCZ696, 400 mg LCZ696, 80 mg valsartan, 160 mg valsartan, 320 mg valsartan, 200 mg AHU377 (which blocks neprilysin alone), or placebo. The primary outcome was the lowering of mean sitting diastolic blood pressure during treatment, calculated as the mean difference in blood pressure between three pairwise comparison doses of LCZ696 versus valsartan (100 mg versus 80 mg, 200 mg versus 160 mg, and 400 mg versus 320 mg). Overall, patients treated with LCZ696 had significant reductions in blood pressure compared with valsartan (a mean drop in sitting diastolic blood pressure of -2.17 mm Hg and sitting systolic blood pressure of -4.20 mm Hg). Over eight weeks, the drop in mean sitting diastolic blood pressure was significantly different for 200 mg LCZ696 versus 160 mg valsartan (-2.97 mm Hg) and for 400 mg LCZ696 versus 320 mg valsartan (-2.70 mm Hg). Source: EurekAlert! 3/16/10

Intensive Blood Pressure, Combined Lipid Therapies Do Not Help Adults with Diabetes

Lowering blood pressure to normal levels--below currently recommended levels--did not significantly reduce the combined risk of fatal or nonfatal cardiovascular disease events in adults with Type 2 diabetes who were at especially high risk for cardiovascular disease events, according to new results from the landmark Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial. Similarly, treating multiple blood lipids with combination drug therapy of a fibrate and a statin did not reduce the combined risk of cardiovascular disease events more than treatment with statin alone. The study of more than 10,000 participants is sponsored by the National Institutes of Health. ACCORD is one of the largest studies ever conducted in adults with Type 2 diabetes who were at especially high risk of cardiovascular events, including heart attacks, stroke, or death from cardiovascular disease. The multicenter clinical trial tested three potential strategies to lower the risk of major cardiovascular events: intensive control of blood sugar, intensive control of blood pressure, and treatment of multiple blood lipids. Results of the ACCORD blood sugar clinical trial were reported in 2008. The lipids targeted for intensive treatment were high density lipoprotein (HDL) cholesterol and triglycerides, in addition to standard therapy of lowering low density lipoprotein (LDL) cholesterol. The results of the ACCORD blood pressure and lipid clinical trials appear online in the New England Journal of Medicine and will be in the April 29 print edition. ACCORD researchers from 77 medical centers in the United States and Canada studied 10,251 participants between the ages of 40 and 79 for an average of 10 years. When they joined the study, all participants were at especially high risk of cardiovascular events because they had pre-existing cardiovascular disease, evidence of subclinical cardiovascular disease, or at least two cardiovascular disease risk factors in addition to diabetes. The researchers caution that the results from the ACCORD clinical trial might not apply to patients who are at lower risk of cardiovascular disease than the ACCORD participants, or to patients with more recently diagnosed Type 2 diabetes. Source: EurekAlert! 3/14/10

Phase IV Trial Initiated for Pelvic Muscle Trainer Device

Athena Feminine Technologies, Inc., in partnership with the National Association of Nurse Practitioners in Women's Health, in March announced the initiation of a nationwide enrollment for Phase IV of the DUETS (Device for Urinary Incontinence, Effectiveness, Tolerability, and Satisfaction) research study for its Athena Pelvic Muscle Trainer™ (PMT). The Athena PMT is a Food and Drug Administration-approved wireless vaginal electrical stimulator available by prescription for women with stress, urge, or mixed incontinence. Kegel exercises can strengthen the pelvic floor muscles, allowing for improved bladder control; however, many women who try these exercises forget to do them or do not do them properly. The Athena PMT is a discreet, tampon-sized device that uses an electrical pulse to mimic Kegels, stimulating the muscle to contract and relax with no effort from the woman. The device has data supporting its safety and efficacy, and has no known side effects. The trial will examine the Athena PMT's effectiveness, in terms of the impact of treatment on stress, urge, and mixed urinary incontinence and sexual health, as well as tolerability and satisfaction with the device among different age, race, and socioeconomic groups. Global impressions of subjects and women's health professionals will also be reported. The 13-week study will also look to determine whether the Athena PMT provides an effective, convenient, and comfortable therapy to limit or control urinary incontinence, time of onset, severity, symptoms, comorbidities, and medical and pharmacological histories. Source: PRNewswire 3/11/10

Effectiveness of New Oral Treatment for Lice Demonstrated

French medical researchers from the AP-HP (Henri Mondor Hospital and Avicenne Hospital) and Inserm (Unit 738 and CIC 202, at Tours) have recently demonstrated the effectiveness of a new molecule in the fight against lice. Faced with the emergence of increasing resistance to conventional treatments by these parasites, this new medication represents a therapeutic alternative to standard treatment. The work was published in the March 11 edition of the New England Journal of Medicine. The multicenter, international study compared the effectiveness of a new oral treatment (oral Ivermectin administered at 400 µg/kg) with that of a conventional antilice treatment (0.5 percent malathion lotion). The trial was conducted by applying one or other of the products twice, at an interval of seven days, to 812 contaminated individuals from 376 families. Ivermectin is a compound from the avermectin family that acts by blocking neurotransmissions in the brains of invertebrates. The results obtained by the researchers showed that 95 percent of the 398 individuals who received Ivermectin were free from lice 15 days after the start of treatment, compared to 85 percent of the 414 individuals treated with malathion. Ivermectin is already available on the market. It is prescribed, in particular, for treatment of scabies. Source: EurekAlert! 3/11/10

Osteoarthritis, Fibromyalgia Patients Needed for Pilot Study

Liquid CMO, LLC, the maker of a new liquid natural supplement formulation of cetyl-myristoleate (CMO), is seeking 65 osteoarthritis and 65 fibromyalgia patients for a pilot study in Phoenix, Ariz., beginning April 12. All participants will be medically supervised by David Arneson, NMD, medical director of the Source Naturopathic Medical Clinic in Phoenix. CMO is a natural ring waxy alcohol (long chain fatty acid) discovered in 1972 by Dr. Harry Diehl, who received U.S. patents on its use as a treatment for rheumatoid arthritis and for osteoarthritis. The new study will focus on CMO's effects on symptoms for osteoarthritis and fibromyalgia over four weeks. Participants will be unpaid in an effort to remain independent, and required to purchase the first bottle of Liquid CMO, a two-week supply, for $92. The second two-week supply is provided at no charge. Source: PRNewswire 3/11/10

Initial Clinical Trial for Cardiac Monitoring System Meets Company's Expectations

Scivanta Medical Corp. in March announced that the results of its initial clinical trial for the Scivanta Cardiac Monitoring System (SCMS) clearly indicate that it can accurately measure cardiac performance as expected by the company. This clinical trial was performed at Kaleida Health/Millard Fillmore Hospital in Buffalo, N.Y. The initial clinical trial was designed to obtain data concerning the safety and efficacy of the SCMS by comparing mean left atrial pressure measurements obtained from the SCMS to left ventricular end-diastolic pressure readings measured in a simultaneous left heart catheterization procedure performed by a cardiologist in the cardiac catheterization unit. These measurements of cardiac performance are used by physicians in the critical evaluation of a patient's cardiac health. In the initial clinical trial, the mean left atrial pressure for five patients, as determined by the SCMS, matched the left ventricular end-diastolic pressure, as determined by the left heart catheterization procedure, within 0.1 mm Hg to 0.5 mm Hg. This translates into a maximum deviation of 3.3 percent for the SCMS data when compared to the left heart catheterization data. These results for the SCMS are considered by Scivanta to be highly accurate. There were no adverse events reported during the course of the initial clinical trial. Source: PRNewswire 3/9/10

Positive Top-Line Results Achieved in Study of Relative Abuse Potential

Acura Pharmaceuticals, Inc. and King Pharmaceuticals, Inc. in March announced that top-line results from its Study AP-ADF-114 (Study 114) demonstrate that two different potentially abused excess oral doses of Acurox® Tablets are significantly disliked compared to equivalent excess oral doses of oxycodone HCl tablets alone (without niacin). All five coprimary endpoints comparing the like/dislike of excess doses of Acurox Tablets to the like/dislike of excess doses of oxycodone HCl tablets alone (without niacin) achieved statistical significance. Study 114 primary endpoint results are supplemented by multiple independently measured secondary endpoints, all of which achieved statistically significant results. The Study 114 design may be reviewed at www.clinicaltrials.gov. Acurox is an investigational new drug product and is not approved for marketing or commercial distribution. Acurox Tablets contain a unique composition of oxycodone HCl, niacin, and essential functional inactive ingredients, and are intended to relieve moderate to severe pain while deterring common methods of prescription drug abuse. Source: Marketwire 3/8/10

Enrollment Completed for Pivotal H1N1 Trial in Mexico

Novavax, Inc. announced in March that the enrollment of more than 3,500 subjects in Mexico has been completed in Stage B of its pivotal 2009 H1N1 virus-like-particle (VLP) pandemic influenza vaccine study. With the 1,000 subjects already enrolled in Stage A of the trial, the enrollment in this pivotal trial is now complete with more than 4,500 subjects, making it the largest clinical trial in the company's history. In Stage B, 2,500 of the healthy volunteers aged 18-to-64 received a 15 mcg single dose of Novavax's unadjuvanted 2009 H1N1 VLP pandemic influenza vaccine candidate, while 1,000 of the subjects received placebo. The 15 mcg single dose regimen was recommended by the data and safety monitoring board after reviewing the results of safety and immunogenicity data from a subset of the 1,000 subjects in Stage A of this trial. These data were recently presented at a meeting sponsored by the World Health Organization in Geneva (presentation available on www.novavax.com). The purpose of the Stage B portion of the study was to evaluate safety. Favorable data from Stage B of this study will position Novavax for possible registration of the 2009 H1N1 VLP pandemic influenza vaccine candidate in Mexico. VLPs mimic the external structure of viruses, but lack the live genetic material that causes viral replication and infection. VLPs can be designed quickly to match individual viral strains and be produced efficiently using portable cell-culture technology. Novavax's VLP-based vaccine candidates are produced more rapidly than egg-based vaccines by using proprietary, portable, recombinant cell-culture technology. Source: PRNewswire 3/8/10

Continuation Study Supports Long-Term Efficacy of Chorea Treatment

Lundbeck Inc. in March announced the presentation of results from an open-label extension study of Xenazine® (tetrabenazine) for the treatment of chorea associated with Huntington's disease. Data from this study demonstrated that after an 80-week treatment period, subjects treated with Xenazine experienced a statistically significant reduction in chorea score, as measured using the Unified Huntington's Disease Rating Scale, compared to baseline. These results are consistent with the reduction in chorea score observed in a pivotal Phase III randomized, double-blind, placebo-controlled, multicenter clinical study in which subjects were treated with Xenazine for 12 weeks. Data from the open-label study were presented at the 12th Annual American Society of Experimental NeuroTherapeutics meeting in Bethesda, Md. Results of this study are published in BMC Neurology, an online open access journal. Xenazine carries a boxed warning for increased risk of depression and suicidality. The jerky, sporadic movements commonly seen with chorea associated with Huntington's disease may make it difficult for affected individuals to perform such tasks as holding objects or walking. The study enrolled 75 subjects, all of whom had previously completed 12 weeks of treatment with Xenazine in the pivotal Phase III trial, followed by a one-week washout period. Xenazine was titrated over a maximum 12 weeks every three to seven days to the best individual dose, up to a maximum of 200 mg/day. Of the 75 subjects enrolled in the study, 45 subjects completed the 80-week treatment period, of which 42 subjects continued on to complete a one-week washout period. Thirty subjects withdrew from the study. Source: EurekAlert! 3/5/10

Phase I Trial Initiated in Patients With ALS

Isis Pharmaceuticals, Inc. announced in March that it has initiated a Phase I study of ISIS-SOD1Rx in patients with an inherited, aggressive form of Lou Gehrig's disease (also known as familial amyotrophic lateral sclerosis [ALS]). Approximately 20 percent of all familial ALS cases are caused by a mutant form of superoxide dismutase, or SOD1. ISIS-SOD1Rx is an antisense drug designed to inhibit the production of SOD1. The ALS Association and the Muscular Dystrophy Association are providing funding for the development of ISIS-SOD1Rx. This is the first study to administer an inhibitor of SOD1 directly into the central nervous system. The placebo-controlled, dose-escalation study is designed to assess the safety, tolerability, and pharmacokinetic profile of ISIS-SOD1Rx in four cohorts with eight patients each. In this study, ISIS-SOD1Rx will be administered intrathecally using an external pump to deliver the drug directly into the spinal fluid during a single, 12-hour infusion. The study will be conducted in multiple centers within the United States. source: PRNewswire 3/5/10

Transplant Drug Preserves Kidneys, Avoids Toxicity

The experimental drug belatacept can prevent graft rejection in kidney transplant recipients while better preserving kidney function when compared with standard immunosuppressive drugs, data from two international Phase III clinical trials show. The results are published in the March issue of the American Journal of Transplantation. The drugs most transplant patients now rely on to inhibit their immune systems and prevent graft rejection have serious side effects. The class of drugs known as calcineurin inhibitors (cyclosporine and tacrolimus, for example) can damage the kidneys and lead to high blood pressure and diabetes. The data from the BENEFIT trial, which tracked 666 kidney transplants at 100 sites around the world, show that patients taking belatacept had graft survival rates similar to those taking cyclosporine, while maintaining higher kidney function and lower blood pressure and cholesterol. In addition, instead of requiring patients to take pills twice every day, in the case of calcineurin inhibitors, belatacept can be given every few weeks. The trial, which was sponsored by Bristol Myers Squibb, compared three regimens: a more intensive and a less intensive course of belatacept treatment, and a standard cyclosporine course. All patients received a temporary course of an anti-T cell antibody called basiliximab, and the standard transplant drugs mycophenolate mofetil and corticosteroids. After one year, the proportion of patients with impaired kidney function (defined through glomerular filtration rate) was 55 percent for more intensive and 54 percent for less intensive, compared to 78 percent for cyclosporine. Patients' blood pressure, cholesterol, and blood sugar profiles were also more favorable with belatacept. More patients experienced acute rejection--a temporary flare-up of the immune system against the donated kidney--under belatacept (22 percent for more intensive, 17 percent for less) compared to 7 percent with cyclosporine. However, in most cases, the acute rejection was successfully treated with drugs and did not lead to graft failure. With belatacept, there was a higher incidence of a serious complication called post-transplant lymphoproliferative disorder (PTLD)--five patients total in the BENEFIT trial, compared to one with cyclosporine. PTLD is associated with infection with the Epstein-Barr virus, which many humans have as a low-level chronic infection. The authors say PTLD might be reduced by avoiding use of belatacept in Epstein-Barr-naïve patients. Source: EurekAlert! 3/3/10

Phase III Alzheimer’s Study Does Not Meet Efficacy Endpoints

Pfizer Inc. and Medivation, Inc. in March announced results from two Phase III trials of the investigational drug dimebon (latrepirdine) in patients with Alzheimer’s disease. In the CONNECTION trial, dimebon did not meet its coprimary or secondary efficacy endpoints compared to placebo. Coprimary endpoints were measures of cognition and global function. Dimebon was well tolerated in both the CONNECTION study and in a separate Phase III safety and tolerability study, which confirmed dimebon’s tolerability when dosed alone or in combination with approved Alzheimer’s disease medicines. CONNECTION is a multinational, double-blind, placebo-controlled safety and efficacy trial involving 598 patients with mild-to-moderate Alzheimer's disease at 63 sites in North America, Europe, and South America. In the study, patients were randomized to one of three treatment groups, receiving dimebon 20 mg three times a day (TID), dimebon 5 mg TID, or placebo TID for six months. No statistically significant improvements for the 20 mg TID group relative to placebo were achieved on the coprimary endpoints. One primary endpoint evaluated the effect of dimebon on cognition, as measured by the Alzheimer's Disease Assessment Scale-cognitive subscale, and showed that dimebon-treated patients achieved a 0.1 point difference from patients receiving placebo. Neither group was significantly changed from baseline. The other primary endpoint evaluated the effect of dimebon on independently rated global function over the course of the six-month trial, as measured by the Clinician's Interview-Based Impression of Change Plus Caregiver Input. According to this scale, 64.9 percent of the patients treated with dimebon 20 mg TID showed improvement or no change at Week 26 compared to 65.4 percent of placebo-treated patients. Results for the dimebon 5 mg dose were similar to the dimebon 20 mg and placebo, although they were numerically lower. The 20 mg TID dimebon-treated patients also showed no statistically significant differences compared to placebo on the secondary efficacy endpoints. The Phase III safety and tolerability study enrolled 742 patients with mild-to-moderate Alzheimer’s disease in the United States and Canada. Dimebon is being studied in four other ongoing randomized, double-blind, placebo-controlled Phase III studies, which currently are enrolling, as well as in the HORIZON trial, a six-month study evaluating dimebon in patients with Huntington's disease. Source: Pfizer press release 3/3/10 For a reaction to this announcement from the Alzheimer Research Forum, click here.

Treatment Increased Survival in Advanced Hormone-Refractory Prostate Cancer

Sanofi-aventis announced results in March from a Phase III trial that demonstrated cabazitaxel, an investigational compound, plus prednisone/prednisolone significantly improved overall survival and progression-free survival in patients with metastatic (advanced) hormone-refractory prostate cancer whose disease progressed following treatment with docetaxel-based chemotherapy. The TROPIC trial compared the combination of cabazitaxel plus prednisone/prednisolone to the active agent mitoxantrone plus prednisone/prednisolone. For many patients with metastatic hormone-refractory prostate cancer, their disease continues to progress despite prior chemotherapy. Currently, there are no approved therapies to treat these patients. Results showed that the combination of cabazitaxel and prednisone/prednisolone significantly reduced the risk of death by 30 percent with a clinically meaningful improvement in the median overall survival of 15.1 months in the cabazitaxel combination arm versus 12.7 months in the mitoxantrone combination arm. Patients who received the combination treatment with cabazitaxel also experienced a significant increase in median progression-free survival (2.8 months versus 1.4 months). TROPIC was conducted in 146 trial sites in 26 countries throughout the world, including the U.S., and assessed 755 patients. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, tumor response rate, tumor progression, prostate-specific antigen (PSA) response, PSA progression, pain response, and pain progression. Disease progression in this trial was defined as tumor progression, PSA progression, or pain progression. Patients were randomly assigned to receive cabazitaxel plus prednisone/prednisolone or mitoxantrone plus prednisone/prednisolone (378 and 377 patients, respectively). Patients were to receive either regimen for up to a maximum of 10 cycles. Source: PRNewswire 3/3/10

Phase II Program Will Study Drug in Combination with RFA for Colorectal Liver Metastases

Celsion Corp. today announced that it will initiate a randomized Phase II study of lyso-thermosensitive liposomal doxorubicin (ThermoDox®) and radiofrequency ablation (RFA) for colorectal liver metastases at the Montefiore Medical Center and Albert Einstein College of Medicine in New York City, and at least two other leading research institutions from North America and the Asia Pacific region, in the second half of 2010. The study is meant to address the growing unmet medical need of colorectal liver metastases, which is globally prevalent and is currently treated by RFA. The company first began studying ThermoDox in combination with RFA in a Phase I safety study of 24 patients, 15 of whom had liver metastases. Source: PRNewswire 3/1/10

Landmark NIH Trial Compares Surgery to Stenting for Stroke Prevention

A major new study of people at risk for stroke showed that two medical procedures designed to prevent future strokes are safe and effective overall. Physicians will now have more options in tailoring treatments for their patients at risk for stroke. In the trial of 2,502 participants, carotid endarterectomy (CEA), a surgical procedure to clear blocked blood flow and considered the gold standard prevention treatment, was compared to carotid artery stenting (CAS), a newer and less invasive procedure that involves threading a stent and expanding a small protective device in the artery to widen the blocked area and capture any dislodged plaque. One of the largest randomized stroke prevention trials ever, the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) took place at 117 centers in the United States and Canada over a nine-year period. CREST compared the safety and effectiveness of CEA and CAS in patients with or without a previous stroke. The trial was funded by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health (NIH), and led by investigators at Mayo Clinic, Jacksonville, Fla., and the University of Medicine and Dentistry of New Jersey in Newark. The overall safety and efficacy of the two procedures was largely the same, with equal benefits for both men and for women, and for patients who had previously had a stroke and for those who had not. However, when the investigators looked at the numbers of heart attacks and strokes, they found differences. The investigators found that there were more heart attacks in the surgical group, 2.3 percent compared to 1.1 percent in the stenting group; and more strokes in the stenting group, 4.1 percent versus 2.3 percent for the surgical group in the weeks following the procedure. The study also found that the age of the patient made a difference. At approximately age 69 and younger, stenting results were slightly better, with a larger benefit for stenting, the younger the age of the patient. Conversely, for patients older than 70, surgical results were slightly superior to stenting, with larger benefits for surgery, the older the age of the patient. Source: NIH press release 2/26/10

Company to Initiate Trials in Europe for Male Sexual Enhancement Drug

Global Health Ventures Inc. in February announced that it has engaged Clinical Investigations Ltd. in the United Kingdom to design and carry out the human clinical trials for X-Excite in Europe under the European Regulatory Guidelines. The study is designed to compare three doses of X-Excite with the current oral formulation of sildenafil citrate (Viagra®) in a randomized open-label study. The focus of the study will be to obtain pharmacokinetics, bioavailability, and the efficacy of X-Excite compared to the existing Viagra® tablets. These trials, which will be conducted in patients with erectile dysfunction, will set up the basis for a larger and more comprehensive trial in North America under Food and Drug Administration guidelines. According to the company, the drug is being developed to work sublingually, thus having a more rapid mode of action, and bypassing all the inconveniences and many side effects associated with other application routs. Source: Marketwire 2/24/10

Phase IIb Enrollment Complete for Liver Cirrhosis Trial

Ocera Therapeutics, Inc. announced in February that the ASTUTE Study (AST-120 Used to Treat Hepatic Encephalopathy) has completed enrollment for its Phase IIb study ahead of schedule, with data expected in mid-2010. AST-120 adsorbs ammonia and other gut derived toxins that factor prominently in the underlying cause of mild hepatic encephalopathy (MHE), a neurocognitive disorder present in a majority of patients with cirrhosis of the liver. Because MHE leads to a change in cognitive function, including personality changes and intellectual impairment, the disorder has a profound negative impact on quality of life. MHE patients are at increased risk of motor vehicle accidents, losing their jobs, and eventually being hospitalized due to acute hepatic encephalopathy. The randomized, double-blind, multicenter study has enrolled 150 patients with MHE; it employed the Repeatable Battery for the Assessment of Neuropsychological Status to screen and evaluate cirrhotic patients for evidence of MHE, and found that MHE was present in more than half of patients screened. Subjects were randomly assigned to receive either AST-120 or placebo for up to eight weeks. The study was designed to evaluate the effects of AST-120 on neurocognitive function using a variety of validated instruments. In addition, quality of life, clinical global evaluations, and safety assessments will be conducted. According to the company, AST-120 adsorbs substances including ammonia, serotonin, histamine, advanced glycation endproducts, and bacterial toxins. The drug has been used chronically by more than 360,000 patients in Japan, where it is already on the market, and studied in more than 3,000 patients worldwide. Source: PRNewswire 2/23/10

Enrollment for U.S. Bridge-to-Transplant Clinical Trial Concludes Early

HeartWare International, Inc. in February announced the conclusion of patient enrollment under its ADVANCE clinical trial, a Food and Drug Administration (FDA)-approved Investigational Device Exemption study designed to evaluate the HeartWare® Ventricular Assist System as a bridge to heart transplantation for patients with end-stage heart failure. The primary endpoint of the trial is survival at 180 days, defined as alive on the originally implanted device or transplanted or explanted for recovery. Secondary endpoints include such adverse events as bleeding and infection, as well as functional status, hospitalization, assessment of neurocognitive function, and patient quality of life. The trial involves 30 U.S. clinical sites implanting a total of 140 patients, making ADVANCE the largest bridge-to-transplant pivotal trial to date. The final implant in ADVANCE was scheduled to occur on February 25, which would result in the final patient reaching the 180-day follow up by the end of August 2010. With completion of the ADVANCE enrollment, HeartWare is seeking approval from the FDA to implant additional bridge-to-transplant patients under a Continued Access Protocol in any U.S. center that implanted a patient under the trial. To advance the clinical development of the HeartWare System, HeartWare has also submitted a protocol to the FDA for a Destination Therapy trial in the U.S., expected to commence in the second quarter of 2010. Source: PRNewswire 2/22/10

Positive Results Seen from Phase II Study in Diabetic Macular Edema

Regeneron Pharmaceuticals, Inc. and Bayer HealthCare AG in February announced that VEGF Trap-Eye showed positive results in a Phase II study in patients with diabetic macular edema (DME). The primary endpoint of the study, a statistically significant improvement in visual acuity over 24 weeks compared to the standard of care in DME, macular laser therapy, was met. Visual acuity improvement was measured by the mean number of letters gained while reading an eye chart over the initial 24 weeks of the study. Patients in each of the four dosing groups receiving VEGF Trap-Eye achieved statistically significantly greater mean improvements in visual acuity (8.5 to 11.4 letters of vision gained) compared to patients receiving macular laser therapy (2.5 letters gained) at week 24. VEGF Trap-Eye was generally well tolerated, and there were no drug-related serious adverse events. In this double-masked, prospective, randomized, multicenter trial, entitled DA VINCI (DME And VEGF Trap-Eye: INvestigation of Clinical Impact), 219 patients with clinically significant DME with central macular involvement were randomized to five groups. The control group received macular laser therapy at week one, and patients were eligible for repeat laser treatments, but no more frequently than at 16 week intervals. Two groups received monthly doses of 0.5 or 2.0 mg of VEGF Trap-Eye throughout the six-month dosing period. Two groups received three initial monthly doses of 2.0 mg of VEGF Trap-Eye (at baseline and weeks 4 and 8), followed through week 24 by either every eight-week dosing or as-needed dosing with specific repeat dosing criteria. Following the initial 24 weeks of treatment, patients continue to be treated for another 24 weeks on the same dosing regimens. Initial one-year results will be available later this year. VEGF Trap-Eye also is currently in Phase III development in wet (age-related) macular degeneration with studies being conducted in the United States and Canada by Regeneron and in Europe, Asia Pacific, Japan, and Latin America by Bayer HealthCare; and in Phase III development for the treatment of central retinal vein occlusion, another major cause of blindness. Source: PRNewswire 2/18/10

PK/PD Data Support Further Development of CCR5 Receptor Antagonist

Pharmacokinetic/pharmacodynamic (PK/PD) data for TBR-652, which is being developed by Tobira Therapeutics for the treatment of HIV infection, show a strong relationship between drug exposure and viral suppression with this next-generation CCR5 receptor antagonist. In a Phase IIa trial involving 54 treatment-experienced HIV infected patients, a 10-day course of once-daily TBR-652 monotherapy produced a median nadir decline from baseline in HIV viral load of up to 1.8 log10 copies/mL. Using a simple inhibitory Emax model, steady state plasma concentrations of TBR-652 were highly correlated with reductions from baseline in HIV RNA levels. The PK/PD model estimated a maximal antiviral effect (Emax) for TBR-652 of ~ 1.5 log10 copies/mL. The plasma concentrations of TBR-652 associated with this Emax were easily achieved at doses of greater than or equal to 75 mg/day. Investigators also observed significant viral load suppression persisting throughout the study's 30-day observation period. Study 652-2-201 was a double-blind, placebo-controlled, dose-escalation trial in which patients were randomized to receive once-daily TBR-652 in the following dosing cohorts: 25 mg (n=8), 50 mg (n=8), 75 mg (n=9), 100 mg (n=10), and 150 mg (n=9); 10 patients were randomly assigned to receive placebo. All patients were HIV treatment-experienced, although none had previously been treated with a CCR5 antagonist. Source: PRNewswire 2/17/10

Company Receives FDA Clearance to Initiate Trial in Meniere's Disease

Otonomy, Inc. in February announced that the U.S. Food and Drug Administration (FDA) has granted clearance of the company's Investigational New Drug application for the clinical trial of OTO-104 in patients with Meniere's disease, a debilitating disorder of the inner ear affecting balance and hearing.The FDA clearance enables Otonomy to move forward with the first clinical trial of a sustained release drug delivered by direct otic injection. Using an approach called intratympanic injection, otolaryngologists deposit the drug into the middle ear via a small perforation in the tympanic membrane (eardrum). This method of drug delivery results in increased drug exposure to the inner ear, where the organs for balance and hearing are located, and minimizes systemic exposure that can cause side effects. The prospective, randomized, placebo-controlled, multicenter, Phase Ib study will concentrate on OTO-104 given as a single injection in subjects with unilateral Meniere's disease. While the primary endpoint of the study is safety and tolerability, a number of efficacy endpoints will be monitored, including the frequency of vertigo attacks experienced by patients pre- and post-treatment. Although there are no FDA-approved drug treatments to control the disease's symptoms, steroid injections appear to provide relief for many patients, as demonstrated in numerous independent physician-sponsored clinical studies. OTO-104 is a proprietary formulation of the steroid dexamethasone designed to provide sustained drug release to the inner ear from a single intratympanic injection. A key component of this formulation is a thermosensitive gel, which increases residence time in the middle ear, thereby enabling higher levels of drug exposure to the inner ear. Preclinical studies confirm the extended release profile of OTO-104 and significant advantage over aqueous formulations, which rapidly drain from the middle ear through the eustachian tube. Sustained release is important to maximize therapeutic effect, enhance drug distribution to the inner ear, and reduce response variability. Source: PRNewswire 2/17/10

Pharmacokinetics Trial Initiated for Migraine Therapy

MAP Pharmaceuticals, Inc. in February announced that it had initiated a single-dose, open-label, crossover trial to compare the pharmacokinetics (PK), safety, and metabolic profiles of Levadex™ orally inhaled migraine therapy to intravenous dihydroergotamine mesylate (DHE) in 24 smokers and 24 nonsmokers. Levadex is a novel therapy that has completed Phase III efficacy development for the acute treatment of migraine. This PK trial is one of two remaining trials to be initiated in support of a New Drug Application (NDA) submission for Levadex as previously requested by the U.S. Food and Drug Administration. In addition to the PK trial, the company is conducting an ongoing 12-month open-label safety extension of its Phase III FREEDOM-301 trial, which has completed enrollment, and also plans to conduct a pharmacodynamic trial. The company anticipates that patients in these trials will complete treatment in 2010. Levadex is a novel formulation of DHE, a drug used intravenously in clinical settings, to effectively and safely treat migraines. It is designed to be differentiated from existing migraine treatments. Based on clinical results, the company believes that the formulation has the potential to provide fast onset of action, sustained pain relief, and other migraine symptom relief in an easy-to-use and noninvasive at-home therapy. Source: PRNewswire 2/16/10 

Hospital Study Demonstrates Safety and Potential Efficacy of Oral Allergy Treatment

An oral allergy treatment administered in drops under the tongue is a safe and effective alternative to injections for adults who are allergic to ragweed pollen, according to a study published in February in the Journal of Allergy and Clinical Immunology by allergic disease specialist at Allegheny General Hospital in Pittsburgh, Pa. Widely used in Europe, but not yet approved by the U.S. Food and Drug Administration, sublingual allergen immunotherapy (SLIT) can be a more convenient and tolerable treatment approach that leads to greater patient compliance, said David Skoner, MD, director of the hospital's Division of Allergy, Asthma, and Immunology and a co-lead investigator in the study. The study involved 115 patients in Pittsburgh, Madison, Wisc., Iowa City, and Evansville, Ind. They were randomly assigned to a medium or high dose of standardized glycerinated short ragweed pollen extract or to a placebo. Participants kept diaries to monitor their symptoms over the course of 17 weeks during the ragweed pollen season. The frequency of daily symptoms, as well as the need for additional medication to treat symptoms, both dropped significantly for those taking the high-dose medication, versus those taking a placebo. The frequency of adverse events was similar between the placebo and treatment groups. The researchers concluded that SLIT was safe and can reduce symptoms in ragweed-sensitive patients, although more trials are needed to definitively establish the method's efficacy. Shortcomings of previous trials with the sublingual method included small patient populations, high withdrawals, and short treatment duration. Questions remaining on SLIT include treatment schedules, optimal doses, and cost-effectiveness. Source: PRNewswire 2/12/10 

Pivotal Clinical Study Launched to Demonstrate Clinical Value of Fluid Shunt System

NovaShunt in February announced the initiation of its pivotal multicenter clinical study named PIONEER, a prospective, open-label, nonrandomized study to investigate the safety and performance of the company's Automated Fluid Shunt (AFS) System in patients with ascites and diuretic resistance. The study concentrates on the use of the system in replacing the need for paracentesis, the standard therapy for patients with refractory ascites. Secondary parameters in the study are concomitant reduction in the need for medication, healthcare costs (hospital stays, treatment), and patients' quality of life. Data from the PIONEER study will be used in an attempt to obtain CE Marking, which will allow NovaShunt to enter the European market. The study is being led by the Principal Investigator Dr. Jose Such, head of hepatology, University General Hospital, Alicante, Spain, and will be initialized in five university hospitals in Europe specialized in managing patients with refractory ascites (located in Alicante, Barcelona, Frankfurt, Regensburg, and London). The AFS System is an implantable, battery powered pump that automatically and continuously removes excess fluid--known as ascites--that builds up in the abdominal cavity in patients with liver disease and other conditions. The majority of patients with ascites can be managed with a sodium-restricted diet and increasingly larger doses of diuretics. However, more than 10 percent of the patients develop refractory ascites and become nonresponsive to diuretic therapy. Source: PRNewswire 2/11/10 

Interim Analysis Backs Continued Enrollment for Blood-Based Acute Appendicitis Test

AspenBio Pharma, Inc. in February reported conclusions from its preplanned, independent, interim analysis of the company's ongoing supplemental clinical trial of AppyScore™, the first blood-based test designed to aid in the evaluation of patients suspected of having acute appendicitis, and outlined next steps for its AppyScore 510(k) filing with the U.S. Food and Drug Administration (FDA). Based on the interim analysis, the trial, currently with more than 600 patients enrolled, will continue enrollment to approximately 800 patients, with completion anticipated in March 2010. Given the time estimate to complete the current trial and related data analysis, the company has withdrawn its 510(k) on file with the FDA and will submit a new 510(k) with full results from the ongoing clinical trial. This clinical trial is statistically sized to stand alone, and thereby becomes the pivotal trial to support the new 510(k) submission. Source: Marketwire 2/9/10 

Study of Concomitant Use of Proton Pump Inhibitors Launched

Takeda Global Research & Development Center, Inc., U.S., announced in February that it has initiated a trial to study how dexlansoprazole (Kapidex™) and several other proton pump inhibitors (PPIs) affect the pharmacokinetics and pharmacodynamics of Plavix (clopidogrel bisulfate) in healthy subjects. Takeda has been evaluating all published data and communications from the U.S. Food and Drug Administration (FDA) regarding the potential risks associated with concomitant use of clopidogrel and PPIs. This clinical trial is currently enrolling subjects and is expected to be completed within the 2010 calendar year. The randomized, open-label, single-center, multiple-dose, two-period, crossover study is designed to assess the effects of multiple oral doses of four once-daily PPIs on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel in healthy subjects. Clopidogrel is a drug that is indicated for the reduction of atherothrombotic events, such as recent myocardial infarction, recent stroke, established peripheral arterial disease, or acute coronary syndrome. According to a recent FDA announcement, studies have shown that omeprazole inhibits a liver enzyme (CYP2C19) important for the activation of clopidogrel. With CYP2C19 inhibition, clopidogrel will have reduced anticlotting effects, thereby reducing its effectiveness. The FDA has recommended that coadministration of omeprazole and other potent CYP2C19 inhibitors, including esomeprazole, be avoided in patients taking clopidogrel. It is unknown how other PPIs may interfere with Plavix. In the interaction study, subjects will be randomized into eight regimen sequence groups, each of which will receive two regimens. The endpoints of this study are to measure plasma concentrations of the active metabolite for clopidogrel and to determine the subject's total exposure to the active metabolite after clopidogrel has been administered with each of the PPIs for nine days. Platelet function will also be assessed prior to and during the trial, as well as 24 hours following the nine-day exposure to each PPI. Source: Marketwire 2/9/10 

Early Artificial Pancreas Trials Show Benefits Overnight

In a landmark study in children and teenagers with type 1 diabetes, Juvenile Diabetes Research Foundation-funded researchers at the University of Cambridge showed that using a first-generation artificial pancreas system overnight can lower the risk of low blood sugar emergencies while sleeping, and at the same time improve diabetes control. Results from the studies are published in the February 5 issue of The Lancet. The trials tested the safety and effectiveness of the system, as used overnight in a hospital setting with participants between 5 and 18 years of age with Type 1 diabetes. The system combined commercially available blood glucose sensors and insulin pumps, controlled by a sophisticated computer program that determined insulin dosage based on blood glucose levels while the participants slept. Notably, the first phase of the Cambridge study showed that the children and teenagers spent twice as much time during the night within targeted blood glucose levels when their diabetes was regulated with the artificial pancreas system than when they followed conventional "manual" therapy. The second phase of the study evaluated the effects of a using the same artificial pancreas system overnight with the additional variable of the participants eating a particularly large meal, which can impact overnight blood glucose levels. The results were comparable to the first phase of the research. The third phase of the study evaluated the effects of moderately intense exercise, which can also impact blood sugar levels. Using the automated system in this setting showed the greatest improvement in blood sugar control. The Cambridge studies were randomized, controlled trials involving 17 children and adolescents conducted at the Wellcome Trust Clinical Research Facility at Addenbrooke's Hospital in Cambridge, United Kingdom over the course of 54 nights. Source: EurekAlert! 2/5/10 

Ponseti Method of Clubfoot Correction Leads to Lower Surgical Rates and Less Revision Surgery

Clubfoot affects one in a thousand babies born in the United States, but with proper corrective treatment and follow-up, infants born with clubfoot can have feet compatible with an active, normal lifestyle. A new study in the February issue of The Journal of Bone and Joint Surgery compared two common treatment options for clubfoot—the Ponseti method and surgical treatment. "While more conservative treatment methods have become popular in the United States over the last several years, surgical treatment has been the primary option in New Zealand until quite recently," explained Matthew Halanski, MD, who authored the study with mentors at the Starship Children's Hospital in Auckland, New Zealand. "This is the first controlled, prospective study to compare the short-term outcomes for clubfeet treated either surgically or with the Ponseti method." Fifty-five patients with 86 clubfeet were treated as part of the study. Forty patients' feet were treated with the Ponseti method, which involves weekly manipulation with above-knee casting often followed by cutting of the Achilles tendon to correct the condition; bracing is then used to maintain the correction. Forty-six were treated with surgery and casting, which involves lengthening of the Achilles tendon and release of the ankle joint, multiple joints in the foot, and often realignment and pinning of the bones in the foot. The average number of casts per patient was six in the Ponseti group and 13 in the surgical group. The study found that among the patients treated, 15 feet in the Ponseti group had a recurrence requiring some surgery (four of these feet had a major recurrence and 11 had a minor recurrence); 14 feet in the surgical group required revision surgery. Patients treated in both groups had a 30 percent to 40 percent rate of relapse. While this is a relatively high recurrence rate for both groups, feet in the Ponseti group needed significantly less invasive operative intervention and required less revision surgery. For patients in the surgical group who required revision surgery, it was actually a repeat procedure, which has been shown in other studies to lead to poorer function. Source: PRNewswire 2/1/10

Phase II Study Considers Treatment of Advanced Waldenstrom's Macroglobulinemia

Keryx Biopharmaceuticals, Inc. in late January announced that an article reporting Phase II data demonstrating the single agent activity of KRX-0401 (perifosine) for the treatment of advanced Waldenstrom's Macroglobulinemia, would appear in the February 1 issue of Clinical Cancer Research. Perifosine, the company's oral PI3K/Akt pathway inhibitor is currently being investigated in a Phase III trial under Special Protocol Assessment for the treatment of advanced multiple myeloma. Similar to multiple myeloma and non-Hodgkin's lymphoma, Waldenstrom's is a hematologic disease in which the cancer cells target the bone marrow. There are currently no drugs approved by the Food and Drug Administration for the treatment of Waldenstrom's. Dr. Irene Ghobrial, assistant professor of medicine in the Bing Center for Waldenstrom's Macroglobulinemia at Dana-Farber Cancer Institute, led the study, in which 37 patients were treated with perifosine 150 mg daily for six cycles. In this study, 41 percent of the patients had three or more lines of prior therapy and 78 percent had two or more prior lines of therapy. Stable or responding patients were allowed to continue therapy until progression. Of the 37 patients, four achieved a partial response, nine achieved a minimal response, and 20 showed stable disease. Overall, 89 percent of patients treated with single-agent perifosine were reported to have stable disease or better, while 11 percent demonstrated progression. The median progression-free survival in the study was 12.6 months, with a median overall survival of 26 months. Source: PRNewswire 1/29/10

Vaccine Approach Extends Life of Metastatic Prostate Cancer Patients

In a newly published clinical trial, patients with metastatic prostate cancer who received a vaccine of harmless poxviruses engineered to spur an immune system attack on prostate tumor cells lived substantially longer than patients who received a placebo vaccine, report researchers at Dana-Farber Cancer Institute and affiliated organizations. The findings will be published by the Journal of Clinical Oncology on its website and later in a print edition. The randomized Phase II study involved the PROSTVAC-VF vaccine, a combination of two weakened poxviruses that have been genetically programmed to produce slightly irregular versions of prostate specific antigen—a protein on the surface of prostate cells that is abnormal in many prostate cancers—and three costimulatory molecules that spur the immune system to a more vigorous attack on tumor cells. The double-blinded trial included 125 patients with metastatic prostate cancer who did not respond to standard, hormone-lowering therapy. Eighty-two of the participants received the vaccine, produced by BN ImmunoTherapeutics, Inc., and 40 received a placebo. At the three-year point after the study, 30 percent of the PROSTVAC-VF patients were alive, versus 17 percent of the control group. The median survival of the vaccine group was 24.5 months, compared to 16 months for the control group. Investigators are planning a Phase III trial that will enroll about 600 patients to further evaluate the vaccine's effectiveness. The Phase II study was supported by funding from the National Cancer Institute. Source: EurekAlert! 1/25/10

First Patient Dosed in Global Registrational Trial of Long-Acting Hemophilia B Therapy

Biogen Idec and Swedish Orphan Biovitrum in January announced that the first patient was dosed in a registrational, open-label, multicenter trial designed to evaluate the safety, pharmacokinetics, and efficacy of the companies' long-acting, recombinant Factor IX Fc fusion protein (rFIXFc) in hemophilia B patients. The trial, called the B-LONG study, will determine the efficacy of rFIXFc in the prevention and treatment of bleeding in approximately 75 previously treated patients with severe hemophilia B. rFIXFc is a fully recombinant clotting factor developed using Biogen Idec's novel and proprietary monomeric Fc-fusion technology. In the B-LONG trial, rFIXFc's ability to prevent bleeding using different dosing regimens will be measured by evaluating the number of breakthrough bleeding episodes annualized over the study period. The study will also evaluate the efficacy of rFIXFc in on-demand and surgical settings, and compare the pharmacokinetics of a single dose of rFIXFc with a single dose of a commercially available recombinant Factor IX product. The companies are also developing a fully recombinant, long-acting Factor VIII Fc fusion protein (rFVIIIFc) for the treatment of hemophilia A. rFVIIIFc is currently being evaluated in a Phase I/IIa, open-label, dose-escalation, multicenter study to evaluate its safety, tolerability, and pharmacokinetics. Source: Marketwire 1/25/10

Enrollment Completed in Phase Ib/II Combination Trial in Acute Myeloid Leukemia

Sunesis Pharmaceuticals, Inc. in January reported that it has completed enrollment in its Phase Ib/II clinical trial evaluating voreloxin, the company's lead compound, in combination with cytarabine, a widely used chemotherapy, in patients with relapsed or refractory acute myeloid leukemia (AML). A total of 110 patients with relapsed or refractory AML were enrolled in this study, including 50 primary refractory or first relapse AML patients enrolled in the expansion Phase II segments of the trial. According to the company, the combination trial has already generated valuable data regarding voreloxin's antileukemic activity, including low 30- and 60-day all-cause mortality and favorable complete remission, safety, and preliminary survival results in a difficult-to-treat patient population. Nearly 300 AML patients have been treated to date, including 113 patients in REVEAL-1, the Phase II single-agent voreloxin study in older patients unlikely to benefit from standard induction chemotherapy. The Phase Ib/II trial is designed to evaluate the safety, pharmacokinetics, and antileukemic activity of escalating doses of voreloxin when administered on days one and four with cytarabine, given either as a continuous infusion of 400 mg/m2 daily for five days or as a two-hour IV bolus of 1 g/m2 daily for five days. A recommended pivotal dose-regimen of voreloxin used in combination with cytarabine has been identified based on results of the trial to date. Voreloxin is a first-in-class anticancer quinolone derivative, a class of compounds that has not been used previously for the treatment of cancer. A Phase II single-agent trial in platinum-resistant ovarian cancer has also completed enrollment. Sunesis expects to begin Phase III testing in AML later in 2010. Source: Marketwire 1/21/10

Global Phase III Trial to Focus on Survival in Lung Cancer

BioNumerik Pharmaceuticals, Inc. in January announced the treatment of the first patients in a global multicenter Phase III clinical trial of Tavocept (BNP7787) in patients with primary adenocarcinoma of the lung, the most common type of lung cancer. In previous studies, Tavocept demonstrated the potential to substantially increase overall and one-year patient survival while concurrently preventing and reducing the incidence and severity of common chemotherapy side effects, as compared to other currently available treatments for advanced lung cancer. Tavocept, originated and developed by BioNumerik, is an investigational new drug with potential for oncology and nononcology indications. Two independent studies of first-line use of Tavocept with chemotherapy found an increase in overall survival of up to 6.7 months in patients with primary adenocarcinoma of the lung. The Phase III Tavocept trial is a randomized, double-blind, placebo-controlled trial to be conducted at approximately 80 to 100 clinical sites in the United States, Russia, Ukraine, Eastern Europe, and Latin America. The primary objective is to confirm whether Tavocept plus taxane and cisplatin chemotherapy significantly increases overall survival in patients with advanced primary adenocarcinoma of the lung compared to taxane and cisplatin treatment alone. Tavocept's ability to prevent or mitigate common chemotherapy-induced toxicities will be prospectively evaluated by prespecified secondary endpoint analyses. BioNumerik estimates that patient enrollment for the trial could be completed in late 2010 to early 2011. Source: PRNewswire 1/21/10

Little Pill Means Big News in the Treatment of MS

A new drug for multiple sclerosis (MS) promises to change the lives of the 100,000 people in the U.K. who have the condition, say researchers at Queen Mary, University of London. A major trial of the oral drug Cladribine—results of which are published in the New England Journal of Medicine on January 20—has shown that it significantly reduces relapse and deterioration of the disease, and goes a long way to eliminating the unpleasant side effects associated with existing therapies. Cladribine can be taken in tablet form for as little as eight to 10 days a year, eliminating the need for regular injections and intravenous infusions otherwise endured by MS sufferers. Cladribine tablets work by suppressing the immune system, thus compromising the disease's ability to further attack the central nervous system. Led by Professor Gavin Giovanonni at Barts and the London School of Medicine and Dentistry, the new study involved more than 1,300 MS patients who were followed for nearly two years and monitored using MRI scans. Patients were given either two or four short treatment courses of Cladribine tablets per year, or a placebo. Compared to patients who were taking a placebo, those taking cladribine tablets were more than 55 percent less likely to suffer relapse, and 30 percent less likely to suffer worsening in their disability due to MS. Source: EurekAlert! 1/20/10 See also PRNewswire

New Treatment Shown to Reduce Recurrence of Debilitating Diarrhea

A combination of two fully human monoclonal antibodies developed by MassBiologics of the University of Massachusetts Medical School and Medarex, a wholly owned subsidiary of Bristol-Myers Squibb Co., when given with standard antibiotics, was shown to reduce recurrence of a debilitating form of diarrhea by 72 percent in patients enrolled in a Phase II clinical trial. The results of the trial are reported in the January 21 New England Journal of Medicine. Clostridium difficile is a common bacterium that can colonize the human gastrointestinal tract. C. difficile can cause disease when patients are treated with antibiotics for other infections and C. difficile then grows unchecked in the gastrointestinal tract, producing large amounts of two toxins, commonly called toxin A and toxin B. The toxins can cause severe diarrhea and damage the lining of the large intestine. The incidence of C. difficile infection (CDI) in the United States is rapidly increasing, with rates doubling from 2000 to 2005. The emergence of an epidemic strain of C. difficile has been implicated in severe outbreaks of CDI in the United States, Canada, and the United Kingdom, and has affected otherwise healthy individuals in the community. The virulence of the epidemic strain has been attributed, at least in part, to the bacteria's markedly increased efficiency in producing both toxins A and B. The epidemic strain appears to cause both more severe illness initially, and a subsequently higher rate of relapse. In the current study, 200 patients with CDI were enrolled in a randomized, double-blind, placebo-controlled trial conducted at 30 locations in the United States and Canada from July 2006 through April of 2008. Patients were divided into two groups and received either a single injection of the two antibodies, or a placebo, in addition to the standard of care antibiotic treatments for CDI. The patients were followed for 84 days to see how many would suffer a recurrence of the disease. The results showed only 7 percent of those patients who received the antibodies suffered a recurrence, while 25 percent of those who received the placebo had a recurrence—a 72 percent reduction in recurrence. Of the 44 patients infected with the epidemic strain of C. difficile, only 8 percent who received the antibodies suffered a recurrence compared with 32 percent of those who received the placebo. The rights to commercialize the two new antibodies against C. difficile toxins have been licensed to Merck & Co. Source: EurekAlert! 1/20/10

Additional Study to Target Advanced Nonsense Mutation Duchenne/Becker Muscular Dystrophy

PTC Therapeutics, Inc. in January announced the initiation of an additional clinical trial of ataluren (PTC124®) in boys and young men with nonsense mutation Duchenne/Becker muscular dystrophy (nmDBMD) who have permanently lost the ability to walk independently. This trial is evaluating the best methods for measuring functional abilities in patients who have lost independent mobility. Patients with nmDBMD develop progressive muscle weakness that leads to deterioration of ambulation, wheelchair dependency, progressive loss of upper limb strength, and eventual respiratory and cardiac failure. The study, which is expected to complete enrollment rapidly, is being funded in part by a $1 million grant from the Muscular Dystrophy Association, and will involve the association's five-center DMD Clinical Research Network and a site in the United Kingdom. This one-year, Phase IIa study is evaluating the safety, pharmacodynamic activity, and pharmacokinetics of ataluren, while assessing the use of several outcome measures of physical, pulmonary, and cardiac function in patients with advanced disease. Approximately 30 patients are being enrolled in the trial. PTC announced in February 2009 that it has completed enrollment of a registration-directed clinical trial in patients with nonsense mutation Duchenne and Becker muscular dystrophy. The trial is a multicenter, randomized, double-blind, placebo-controlled study to determine whether ataluren can improve walking, activity, muscle function, and strength, and whether the drug can safely be given for a long period of time. Results from this trial are expected to be available in the first half of 2010. PTC Therapeutics has an exclusive collaboration with Genzyme Corp. for the development and commercialization of ataluren. PTC Therapeutics will commercialize ataluren in the United States and Canada, while Genzyme will commercialize the product in other regions of the world. Source: PRNewswire 1/19/10

Positive Results Reported from Phase Ib Trial in Metastatic Breast Cancer

Bionovo, Inc. announced in January the publication of results from its Phase Ib clinical trial of Bezielle (BZL101), an oral drug for metastatic breast cancer. The results of the study, available online in Breast Cancer Research and Treatment, demonstrate that Bezielle continues to be safe and well tolerated, with clinical evidence of anticancer activity in a heavily pretreated population of women diagnosed with metastatic breast cancer. The purpose of the trial was to identify the maximum tolerated dose of Bezielle and to determine the drug's safety and feasibility. A total of 27 women with late-stage breast cancer were enrolled after failing an average of six prior therapies since diagnosis with metastatic breast disease; expected survival pretrial was 90 to 120 days. To date, a total of 48 women with advanced breast cancer have been treated with Bezielle in two early-phase trials. In this trial, independent radiology showed six patients had stable disease and three had evidence of tumor regression consistent with a minimal tumor response. An 80-patient Phase II trial will commence at 16 clinical centers in the United States once funding is secured. Bezielle targets diseased cells while leaving normal cells healthy and intact by stopping the production cycle of energy in cancer cells through the inhibition of glycolysis. This leads to DNA damage and cell death in cancer cells while normal cells remain largely unharmed. Source: PRNewswire 1/14/10

Phase III Trial to Evaluate Drug for Type 2 Diabetes Completes Enrollment

Spherix Inc. in January announced the completion of patient enrollment in its global Phase III clinical trial NEET (70971-004), which is evaluating the safety and efficacy of D-tagatose as an oral treatment for Type 2 diabetes mellitus. The company expects the efficacy results to be available as soon as mid-year, with the maintenance phase of the trial continuing through 2010. NEET (Naturlose [D-tagatose] Efficacy Evaluation Trial) is a global, one-year, multicenter, placebo-controlled, double-blinded, randomized, parallel clinical study of 332 patients to evaluate the safety and effectiveness of D-tagatose on glycemic control in subjects with Type 2 diabetes under diet control and exercise. The duration of the efficacy portion of the trial was reduced from 12 to six months in a protocol amendment submitted to the Food and Drug Administration (FDA) last September. The cardiovascular safety-testing portion of the trial totals 12 months. In December 2008, after the initiation of the trial by Spherix, the FDA issued a Guidance for Industry that held that sponsors of diabetes drug trials should demonstrate that the therapy will not result in an unacceptable increase in cardiovascular risk. A global Phase II trial (70971-005) to determine the minimum dose of D-tagatose affecting the primary and secondary endpoints is also under way. NEET concentrates on D-tagatose as monotherapy over the dosing period, and as an adjunct to diet and exercise. The study is powered to detect a 0.5 percent change in HbA1c, as its primary endpoint, with secondary endpoints establishing glucose, insulin, and lipid profiles and measuring changes in body weight. The primary efficacy analysis will compare the change in HbA1c in patients receiving D-tagatose versus placebo. The study is currently under way at more than 40 clinical research sites in the U.S. and India. Source: PRNewswire 1/12/10

New Drug Considered for Treating Painful Menstrual Cramps

Clinical research centers in Salt Lake City, Utah, and Austin, Texas, have joined an international Phase II trial program to test an experimental new drug designed to treat painful menstrual cramps, or dysmenorrhea, a condition that affects between 45 and 90 percent of women of childbearing age in the United States. Although not life threatening, dysmenorrhea can be debilitating and psychologically taxing, and is one of the leading causes of absenteeism from work and school. Current therapies for the condition (including NSAIDs and off-label oral contraceptives) are not completely effective for all women, and sometimes do not provide satisfactory relief of symptoms, particularly in women with more severe pain. The investigational new drug, presently named VA111913, is designed to tackle the cause of the cramps that can leave some women bedridden, rather than just the symptoms. The Jean Brown Research center in Utah and Premier Research in Texas are recruiting women of childbearing age who suffer from dysmenorrhea and normally take medicines to treat their menstrual cramps to take part in a trial of VA111913, which, in earlier studies, has been shown to control abnormal contraction of smooth muscle, such as that found in the uterus wall. By targeting receptors of a hormone called vasopressin, it is hoped the investigational new drug will prove effective in controlling the abnormal contractions that cause period pain. Results from the study, which involves centers in the U.S. and the U.K., are expected in 2010 and if it, and further studies, are successful, the drug could be available in four years. According to physicians leading the trial, there is currently no targeted therapy to treat the condition. The trial is being sponsored by U.K.-based company Vantia Therapeutics, which discovered the new drug. Source: PRNewswire 1/11/10

Phase I Dosing of Dengue Virus Monovalent Vaccine Completed

Hawaii Biotech, Inc. announced in January that it has completed recruitment and dosing in a multiple dose Phase I clinical study of its dengue virus monovalent vaccine. The double-blind, placebo-controlled, dose escalation safety study in healthy subjects is being conducted at the Saint Louis University Center for Vaccine Development. Vaccine recipients in this study are being monitored for safety as well as for development of virus neutralizing antibodies. President and CEO Elliot Parks, PhD, indicated that preliminary safety results and immunologic data from the healthy volunteers treated with three doses of the vaccine will be available later this quarter. Complete results are expected to be announced by fourth quarter 2010. Hawaii Biotech is developing a dengue virus subunit vaccine designed with high fidelity to the native viral antigens in order to provide protective immunity to the recipients. The vaccine is nonreplicating and designed to be safer than live-attenuated vaccines. The company furthermore hopes to initiate clinical studies with a dengue virus tetravalent vaccine later this year. Infection with dengue virus results in severe flu-like symptoms that can lead to a life-threatening hemorrhagic fever. During the last 25 years, many tropical regions of the world have seen an increase in dengue cases. The southern United States is potentially susceptible to dengue epidemics as the types of mosquitoes that transmit dengue virus are prevalent there. Dengue cases were reported in southern Florida in late 2009. Source: Marketwire 1/7/10

Positive Results Seen in Phase II Study in Obstructive Sleep Apnea

Vivus, Inc. in January announced positive results from a Phase II study evaluating the safety and efficacy of Qnexa®, an investigational drug, for the treatment of obstructive sleep apnea (OSA). The company recently completed Phase III development of Qnexa for the treatment of obesity and submitted a New Drug Application to the Food and Drug Administration for that indication. The study announced in January demonstrated statistically significant improvement in the apnea/hypopnea index (a measure of the severity of sleep apnea) in patients with OSA treated with Qnexa for 28 weeks. Qnexa-treated patients also experienced significant weight loss, improvements in blood pressure, and overnight blood oxygen levels. Currently, there are no approved pharmacologic treatments for OSA. The Phase II study (OB-204) was a single-center, randomized, double-blind, placebo-controlled parallel group trial including 45 obese men and women, 30 to 65 years of age. In addition to receiving active or placebo drug, all patients were provided with an intensive lifestyle modification program. Among other results, on average, patients treated with Qnexa for 28 weeks had a 69 percent reduction in sleep apnea events; treatment reduced the number of apnea/hypopnea events from a mean of 46 events per hour of sleep to 14; treated patients lost 10.2 percent body weight in 28 weeks; and systolic blood pressure was reduced by 15 mm Hg in the Qnexa group from a mean of 138 mm Hg at baseline. Source: PRNewswire 1/7/10

Enrollment for Aneurysm Coiling Trial Completed

Boston Scientific Corp. in January announced that it has completed enrollment in its MAPS™ clinical trial, which is studying the coiling of intracranial aneurysms. This prospective, randomized trial commenced enrollment in 2007 and has reached its goal of 630 patients, enrolled at 47 hospitals in 11 countries. Principal investigators for the trial are Anil Gholkar, OBE, MBBS, Clay Johnston, MD, PhD, and Cameron McDougall, MD. The MAPS trial compares clinical outcomes in patients treated with either bare-platinum GDC® Detachable Coils or Matrix2® Detachable Coils, which are covered with a bio-polymer. The primary endpoint is Target Aneurysm Recurrence at one year, a composite clinical endpoint of target aneurysm rupture or re-rupture, re-treatment or neurologic death. Secondary angiographic endpoints will be compared to the primary clinical outcomes over several years to evaluate the long-term predictive value of 12-month angiography. "The MAPS trial has significant potential to enhance our understanding of the products we use to treat intracranial aneurysms as well as our methods for assessing outcomes," said Dr. Gholkar. "By conducting rigorous measurement, monitoring and adjudication of clinical outcomes over multiple years, the MAPS trial will establish a critical baseline from which to judge existing treatments as well as future endovascular technologies." Source: PRNewswire 1/5/10

Phase IIa Trial of Aerosol for COPD Yields Positive Results

Pearl Therapeutics Inc. in January announced positive results from its first clinical trial in patients with chronic obstructive pulmonary disease (COPD). Results from a Phase IIa dose-ranging study of PT005, the company's formoterol fumarate hydrofluoroalkane metered dose inhaler (HFA-MDI) formulation, showed that it was well tolerated with bronchodilator efficacy and safety outcomes comparable to the active control drug Foradil® Aerolizer® (formoterol from a capsule-based, unit dose, dry powder inhaler). Pearl plans to present results from the study at a future medical conference. Formoterol fumarate is a beta2 agonist bronchodilator that is indicated for the management of asthma and COPD and administered twice daily. The study also identified the optimal dose of formoterol to be used in Pearl's combination therapy program. Pearl is currently advancing PT005 aggressively in combination with PT001, its glycopyrrolate inhalation aerosol, a long-acting muscarinic antagonist bronchodilator, as the first and only dual long-acting rapid bronchodilator combination product in an HFA-MDI delivery format. Source: PRNewswire 1/4/10

Phase III Trial of Drug for Non-Small Cell Lung Cancer Discontinued

Pfizer Inc. announced in late December the discontinuation of A4021016 (also known as ADVIGO 1016), a Phase III trial examining the effects of investigational compound figitumumab (CP-751,871) as first-line treatment in patients with advanced non-adenocarcinoma non-small cell lung cancer (NSCLC) due to the study meeting predefined boundaries for early termination. An analysis by an independent data safety monitoring committee (DSMC) showed that the addition of figitumumab to paclitaxel plus carboplatin would be unlikely to meet the primary endpoint of improving overall survival compared to paclitaxel plus carboplatin alone. This discontinuation follows a halt in new patient enrollment to A4021016 in September 2009, when the DSMC observed an apparent imbalance of certain serious adverse events between the treatment arms with more events, including fatalities, occurring in patients who were randomized to receive figitumumab. The Phase III study was initiated based on robust findings from a Phase II study that identified patients of squamous cell histology, the most common form of non-adenocarcinoma and a disease with a high unmet medical need, as those who could potentially benefit most from figitumumab treatment. The company has notified A4021016 clinical investigators and has initiated the notification procedure for all involved regulatory agencies of the discontinuation of A4021016. Investigators have been instructed to work with all of their patients in the A4021016 study on an individual basis to determine an appropriate course of action. A4021016 is part of a global Phase III clinical trial program called ADVIGO (ADVancing IGF-1R in Oncology), which is studying figitumumab in patients with NSCLC. The program also includes A4021018 (also known as ADVIGO 1018), an ongoing study in patients with refractory advanced non-adenocarcinoma NSCLC that is evaluating figitumumab with erlotinib compared to erlotinib alone. A4021017 (also known as ADVIGO 1017), is a Phase III trial that will evaluate figitumumab in combination with another chemotherapy regimen--cisplatin and gemcitabine--as first-line treatment of advanced NSCLC. This trial is still in the planning stage, and will incorporate lessons learned from ADVIGO 1016 into the final design. In addition to NSCLC, Pfizer is studying figitumumab in clinical trials for the potential treatment of other cancers, including prostate and breast cancers, and Ewing’s sarcoma. Source: Pfizer press release 12/29/09

Company Files Trial Application for Vaccine Against Hand, Foot, and Mouth Disease

Sinovac Biotech Ltd. announced in December that it had filed an application with China's State Food and Drug Administration (SFDA) to commence a human clinical trial for its vaccine against human enterovirus 71 (EV 71), which causes hand, foot, and mouth disease (HFMD). This is the first clinical trial application for HFMD vaccine submitted in China. No vaccine or antiviral treatment is currently available for HFMD worldwide, although it has become a very serious problem in Asia in recent years. The disease is highly contagious, and a growing number of HFMD cases have been reported in parts of Asia, especially among infants and children in Mainland China, Hong Kong, Singapore, Korea, and Taiwan. Due to the severity of the disease epidemic, China authorities recognize the unmet medical need and are expected to support the launch of a HFMD vaccine as soon as possible. Therefore, Sinovac believes that fast track status for the reviewing process and approval may be granted. The company began preclinical development in 2008. Sinovac is independently developing the EV 71 vaccine and will retain full commercialization rights of the vaccine upon approval. Created by Sydney University, the animal model showed cross protection and demonstrated that the vaccine is effective in animals. In addition, Sinovac is preparing to file a patent application covering the EV 71 vaccine. For the first 11 months of 2009, more than 1.1 million cases of HFMD were reported in China, with more than 400 reported fatalities. Source: PRNewswire 12/28/09

Development of Investigational Niacin Receptor Agonist for Atherosclerosis is Discontinued

Arena Pharmaceuticals, Inc. announced in December that Merck and Co., Inc. had decided to discontinue development of MK-1903, an investigational niacin receptor agonist to treat atherosclerosis being developed under its research collaboration with Arena. Merck made the decision to discontinue development of MK-1903 following evaluation of the results of a recently completed Phase IIa clinical trial. The randomized, double-blind, placebo-controlled trial evaluated the safety, tolerability, and potential efficacy in patients with dyslipidemia. According to Merck, elevation of HDL cholesterol relative to placebo did not meet the trial's prespecified primary objective for efficacy; no safety signals were implicated as drivers of the decision to discontinue development. "We are disappointed that the trial results did not lead to further development of this program, but it has been a pleasure to work with Merck and we welcome the opportunity to collaborate again," said Jack Lief, Arena's president and chief executive officer. Source: PRNewswire 12/23/09

Positive Results Seen in Phase III Trials of Diabetic Macular Edema Treatment

Alimera Sciences, Inc. in December reported top-line results from the month 24 readout of the FAME Study, which consists of two Phase III pivotal clinical trials (Trial A and Trial B) for the use of Iluvien in the treatment of diabetic macular edema (DME). The primary efficacy endpoint for the FAME Study is the difference in the percentage of patients whose best corrected visual acuity (BCVA) improved by 15 or more letters from baseline on the ETDRS eye chart at month 24 between the treatment and control groups. The month 24 analysis using the Full Analysis Set in Trial A demonstrated statistical significance, with 26.8 percent of the low-dose patients and 26 percent of the high-dose patients having an improvement in BCVA of 15 letters or greater over baseline. In Trial B, the data demonstrated statistical significance with 30.6 percent of the low-dose patients and 31.2 percent of the high-dose patients having the desired BCVA improvement. The Full Analysis Set includes more than 950 patients randomized into the FAME Study, with data imputation employed using last observation carried forward for data missing because of patients who discontinued the trial or are unavailable for follow up. Over the 24-month period, 2.1 percent of patients receiving the low dose and 5.1 percent of the patients receiving the high dose had undergone a trabeculectomy (filtration procedure) to reduce their eye pressure. Based on these and other data, Alimera plans to seek approval of the low dose of Iluvien for the treatment of DME in the second quarter of 2010, followed by registration filings in various European countries and Canada. Although submission of the New Drug Application will be based on the month 24 safety and efficacy data, the FAME Study will continue to month 36. The multicenter, randomized, double-masked trials for Iluvien were conducted in 101 sites across the United States, Canada, Europe, and India. Iluvien is an investigative, extended-release intravitreal insert designed to provide a therapeutic effect of up to 36 months by delivering sustained submicrogram levels of fluocinolone acetonide. Iluvien is inserted in the back of the patient's eye to a position that takes advantage of the eye's natural fluid dynamics with a device that employs a 25-gauge needle, which allows for a self-sealing wound. Source: PRNewswire 12/23/09

Phase II Trial Shows Drug is Well Tolerated in Patients with Severe Sepsis

The investigational compound, eritoran tetrasodium (E5564) appeared to be well tolerated in patients with severe sepsis in a Phase II trial published in the January issue of Critical Care Medicine. The trial evaluated two doses of eritoran, low-dose (45 mg given every 12 hours for six days) and high-dose (105 mg given every 12 hours for six days), along with a placebo group. The randomized, double-blind, placebo-controlled, multicenter, ascending-dose trial was conducted in intensive care units (ICUs) in the United States and Canada with 300 patients randomized to three groups: 96 received placebo, 103 received eritoran low-dose, and 94 patients received eritoran high-dose. Seven patients did not receive any trial drug and were not included in the modified intent to treat population for analysis. Eritoran or placebo doses were administered via intravenous infusion within 12 hours of recognition of severe sepsis and repeated every 12 hours for six days. The mortality in the placebo, low-dose, and high-dose groups was 33.3 percent, 32 percent, and 26.6 percent, respectively. Although not statistically significant, the difference in mortality between the high-dose group and placebo was 6.7 percent. The greatest benefit was observed in the population at the highest risk of mortality as assessed by APACHE II Predicted Risk of Mortality. In patients who were considered at higher risk of death, mortality among placebo patients was 56.3 percent versus 33.3 percent in high-dose patients. Based on the trial results, Eisai is now conducting a global Phase III clinical trial program, called ACCESS (A Controlled Comparison of Eritoran tetrasodium and Placebo in Patients with Severe Sepsis). The trial will further evaluate eritoran as a potential treatment for severe sepsis, the second most frequent cause of death in intensive care patients in the U.S. In the European Union, sepsis is the most common cause of death in ICUs. The ACCESS trial population will enroll substantially more patients than the Phase II trial, and has been sized (n=2,000) to determine the efficacy (reduction in 28-day all-cause mortality) of eritoran and targets a population with severe sepsis that has a moderate-to-high risk of mortality as determined by baseline APACHE II scores from 21 to 37. APACHE II is a severity of illness scoring system commonly used in sepsis research and ICUs. Source: PRNewswire 12/22/09

Phase I/II Clinical Trial Initiated for the Prevention of Acute Radiation Enteritis

Soligenix, Inc. announced in December that it had initiated a Phase I/II clinical trial evaluating SGX201, a time-release formulation of oral beclomethasone 17,21-dipropionate (oral BDP), for the prevention of acute radiation enteritis. This study will be supported in large part by a two-year Small Business Innovation Research grant of approximately $510,000. The trial is designed as a multicenter, open-label, sequential, dose-escalation study in approximately 36 patients. Patients with rectal cancer who are scheduled to undergo concurrent radiation and chemotherapy prior to surgery will be enrolled in one of four escalating dose groups. The objectives of the study are to evaluate the safety and maximal tolerated dose of escalating doses of SGX201, as well as the preliminary efficacy of SGX201 for prevention of signs and symptoms of acute radiation enteritis. The study is expected to be completed in the first half of 2011. Acute radiation enteritis is an unmet medical need and caused by radiation-induced death of cells in the lining of the bowel. As bowel cells die and are not replaced, gastrointestinal toxicity develops over the next few days and weeks due to an inflammatory response to dead cells and bacteria, with chronic diarrhea, vomiting, and pain being the major symptoms. The addition of chemotherapy often exacerbates the onset, severity, and debilitation related to intestinal symptoms and itself can cause significant gastrointestinal toxicity. This treatment-related enteritis often results in delay or interruption of the cancer treatment. SGX201 contains BDP, a highly potent, topically active corticosteroid that has a local effect on inflamed tissue. BDP has been marketed in the United States and worldwide since the early 1970s as the active pharmaceutical ingredient in inhalation products for the treatment of patients with allergic rhinitis and asthma. BDP is also the active ingredient in orBec®, currently in Phase III and Phase II development by Soligenix for the treatment and prevention of acute graft-versus-host disease, respectively. SGX201 is a time-release formulation of BDP specifically designed for oral use. SGX201 has been awarded fast-track designation from the Food and Drug Adminstration for the treatment of radiation enteritis. Source: PRNewswire 12/21/09

Positive Phase I Results Reported for New Targeted Lung Cancer Therapy

Bryan Oncor in December reported the results of a Phase I trial of its targeted radiopharmaceutical therapy using Re-88 P2045, a radiolabeled synthetic peptide, for the treatment of advanced lung cancer. The trial was conducted at the University of Maryland and the University of Iowa and published in the December issue of the Journal of Thoracic Oncology. This novel approach to cancer treatment combines a synthetic peptide molecule, P2045, which targets over-expressed somatostatin receptors (SSTR) on tumors, with a radioactive isotope, Re-188, which has been shown to destroy cancer cells. The trial results demonstrate that Re-188 P2045 is well tolerated, and that targeting SSTRs using this approach is feasible. Martin Magram, MD, an author of the published paper, comments, "This targeted, personalized approach to therapy has the potential to treat a large unmet need in cancer treatment. Somatostatin receptors are expressed not only in lung cancer, but in several other types of tumors, as well." This targeted approach can reduce the risk of toxicity to patients in two ways. First, it enables screening to determine which patients are most likely to benefit from the treatment. Second, because the radiolabeled peptide is bound to the SSTRs on the cancer cells, the dose is concentrated at the tumor site. While the Re-188 P2045 is retained at the tumor, it clears quickly from the blood, minimizing "off-target" systemic exposure. All of the patients in the trial had advanced lung cancer and entered the study with progressive disease. More than half of the patients had stable disease at eight weeks with overall survival of more than 11 months. "We're very encouraged by the results of the Phase I trial, and are planning further studies to demonstrate the effectiveness of targeted RE-P2045 therapy," said Christopher Adams, cofounder of Bryan Oncor. Source: Marketwire 12/21/09

First ALS Stem Cell Trial to Commence in Georgia

Neuralstem, Inc. in December announced that its Phase I trial to treat amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) with its spinal cord stem cells has been approved by the institutional review board at Emory University in Atlanta, Ga. The trial, which was approved by the Food and Drug Administration (FDA) in September, will take place at the Emory ALS Center, under the direction of Jonathan Glass, MD, director of the center, who will serve as the site principal investigator (PI). The trial will study the safety of Neuralstem's cells and the surgical procedures and devices required for multiple injections of the cells directly into the grey matter of the spinal cord. The Emory ALS Center has posted the relevant trial information for patients on its website. Neuralstem expects to begin treating patients with the stem cells in January and to ultimately treat 18 ALS patients with varying degrees of the disease. The FDA has approved the first stage of the trial, which consists of 12 patients who will receive five-to-10 stem cell injections in the lumbar area of the spinal cord. The patients will be examined at regular intervals postsurgery, with final review of the data to come about 24 months later. The overall PI for the Neuralstem ALS trial program is Eva Feldman, MD, PhD, director of the University of Michigan Health System ALS Clinic and the Program for Neurology Research and Discovery. Source: PRNewswire 12/18/09

Company Discontinues Phase II Glioblastoma Multiforme Trial

Thallion Pharmaceuticals Inc. announced in December that it was closing its Phase II trial evaluating TLN-4601 as a treatment for glioblastoma multiforme (GBM) due to a lack of measurable efficacy after analysis of the interim data. The company's decision to close the study follows a recommendation by the study committee, comprised of the medical investigators leading the clinical trial. "Although we are disappointed by the results of the study, the decision to close the TLN-4601 trial will allow us to focus our resources on programs with more immediate commercial potential. On behalf of Thallion, I would like to thank our clinical investigators and the patients that participated in the GBM trial," said Lloyd M. Segal, chief executive officer of Thallion. The planned interim analysis was conducted after enrolling 20 of the targeted 40 patients in the open label trial. Study results showed that only three out of 17 evaluable patients demonstrated stable disease after two cycles (six weeks) of treatment. No stable disease was observed after four cycles of treatment. TLN-4601 was considered as generally safe and well tolerated. In the absence of any meaningful clinical response, the study committee recommended to the company that the study be stopped. Thallion intends to complete a full analysis of the data package prior to making a decision on the next steps for the TLN-4601 program, including its partnership potential. In the trial, TLN-4601 was continuously administered intravenously at a dosage level of 480 mg/m2/day over 14 days, followed by seven days off treatment (three-week cycles). The primary endpoint of the open-label trial was six-month progression free survival, with secondary endpoints including tumor response, progression-free survival at 12 months, and overall survival. TLN-4601 is a novel small molecule derived from a nonpathogenic microorganism. Phase I clinical testing showed the compound to be safe and well tolerated, with early signs of antitumor activity. TLN-4601 was being evaluated based on its proposed mechanism of action and preclinical animal data demonstrating that the compound crosses the blood brain barrier and appears to preferentially accumulate within brain tumors. Source: Marketwire 12/18/09

Phase IIb Data Reported from Clinical Program for Postsurgical Pain Product

DURECT Corp. in December announced positive results from a 60-patient Phase IIb clinical trial of POSIDUR™, a proprietary product under development for the treatment of postsurgical pain. Top-line results from this study of patients undergoing arthroscopic shoulder surgery showed a consistent reduction of pain scores in parallel with a reduction of opioid use in favor of the drug versus placebo. However, these reductions were not statistically significant given the size of the study. There was a comparable safety profile between the two groups in this study and POSIDUR appeared well tolerated. The company looks forward to commencing enrollment of its U.S. Phase III program in the first quarter of 2010. The double blind, multicenter, placebo-controlled, parallel group trial in patients undergoing arthroscopic shoulder surgery randomly assigned eligible patients to one of two treatment groups prior to surgery (SABER™-bupivicaine [POSIDUR] or SABER-placebo). Supplemental rescue analgesia for postoperative shoulder pain in both treatment groups was provided if needed. The study was conducted at sites in Australia and New Zealand. The drug is intended to be administered during surgery, where it continuously releases therapeutic levels of bupivacaine in a controlled fashion, providing up to 72 hours of uninterrupted local analgesia. Source: PRNewswire 12/17/09

Top-Line Phase IIb Results Announced for Peyronie's Disease Treatment

Auxilium Pharmaceuticals, Inc. in December announced top-line efficacy and safety results for the Phase IIb clinical trial for Xiaflex™ (collagenase clostridium histolyticum) in the treatment of Peyronie's disease. The study was designed to measure efficacy endpoints of improvement in penile curvature and improvement in patients' sexual quality of life using the company's Peyronie's disease Patient Reported Outcome (PRO) questionnaire. Overall, Xiaflex demonstrated a statistically significant change compared to placebo at 36 weeks in both improvement in penile curvature and the PRO Peyronie's disease bother domain. Xiaflex was well tolerated, and the most common treatment related adverse events in the study were consistent with adverse events reported in previous Peyronie's disease trials with Xiaflex, which included injection site bruising, edema, and pain. The company expects to meet with the U.S. Food and Drug Administration in the second quarter of 2010 to discuss a proposed Phase III plan that potentially could be started in the second half of 2010. The current trial is one of the largest prospective, randomized, placebo-controlled studies conducted in Peyronie's disease. A total of 145 patients evaluable for efficacy enrolled in 12 clinical sites across the U.S., with 109 patients receiving Xiaflex as a series of intralesional injections and 36 receiving placebo (3:1 ratio) in the study. The treatment and placebo arms were also randomized to test for a benefit with the addition of penile modeling versus no modeling (1:1). Modeling refers to massaging of the plaque, and is intended to maximize the enzymatic effect of the Xiaflex injection in the plaque. There were no statistically significant changes in mean scores between Xiaflex and placebo in the PRO penile pain, intercourse discomfort, or intercourse constraint domains. Source: Marketwire 12/16/09

Drug for Alzheimer's Disease Does Not Appear to Slow Cognitive Decline

Although there were promising results in a Phase II trial, patients with mild Alzheimer's disease who received the drug tarenflurbil as part of a Phase III trial did not have better outcomes on measures of cognitive decline or loss of activities of daily living compared to patients who received placebo, according to a study in the December 16 issue of the Journal of the American Medical Association. A leading theory on the pathophysiology of Alzheimer's disease is the overproduction of amyloid-ß (Aß; a peptide of certain amino acids that appear to be the main constituent of amyloid plaques in the brains of patients with the disease), particularly 42 amino acid peptide Aß42. "Tarenflurbil, a selective Aß42-lowering agent, demonstrated encouraging results on cognitive and functional outcomes among mildly affected patients in an earlier Phase II trial," the authors write. Robert C. Green, MD, MPH, of the Boston University Schools of Medicine and Public Health, and colleagues conducted a large Phase III, randomized trial of tarenflurbil for patients with mild disease to determine its efficacy, safety, and tolerability. The study, conducted at 133 trial sites in the United States, included 1,684 participants who were randomized, of whom 1,649 were included in the analysis, and 1,046 completed the 18-month trial. Patients were randomized to tarenflurbil, 800 mg, or placebo, administered twice a day. The researchers found that tarenflurbil had no beneficial effect on the primary outcomes of cognition and activities of daily living after 18 months. There were also no significant differences on secondary outcomes, which included other disease assessment measures, such as quality of life and caregiver burden. Regarding adverse events, more participants taking tarenflurbil than those taking placebo experienced dizziness, upper respiratory tract infections, and anemia. "Our results are a reminder that interventions affecting amyloid have not yet been shown to alter the course of [the disease]," the authors conclude. Source: EurekAlert!12/15/09

Microbicide Trial Results Disappointing, Researchers and Volunteers Deserve Praise

The Microbicides Development Programme of the AIDS Vaccine Advocacy Coalition announced in December that its MDP 301 effectiveness trial, which was conducted among almost 9,400 women in four African countries, found no evidence that the PRO 2000 microbicide reduces the risk of HIV infection. Although this product had looked promising in animal studies and in earlier human studies, the MDP 301 trial provided a clear answer that this product does not work. The trial organizers say that a trial of this complexity and magnitude is a great accomplishment in the effort to stem the tide of the HIV pandemic. They add that, everyone involved, especially the trial staff and volunteers, deserve thanks and credit for their dedicated efforts and important contributions. While this trial did not result in an effective product, it was a successful trial--it gave a clear result, even if that result is disappointing. In many ways, this trial should serve as a model for future HIV prevention trials, as it will provide critical scientific information as well as important lessons from the extensive social science component and the comprehensive community engagement and preparation undertaken by the trial staff. The principal investigators and trial staff developed several innovative integrated approaches for working with participants and communities to ensure retention in the trial and to track women's use of the product. Today, there are many more HIV prevention options in large-scale trials, including vaccines, other microbicides with different mechanisms of action, and oral pre-exposure prophylaxis--antiretroviral drugs being tested for prevention. Important results from these trials are anticipated in 2010 and beyond. In addition, in the last few years, clinical trials have also shown that medical male circumcision can be effective at preventing HIV infection in heterosexual men. More recently, in October, results from a large clinical trial with more than 16,000 participants in Thailand provided evidence for the first time that it is possible to reduce the risk of HIV infection with a vaccine. Source: PRNewswire 12/14/09

Primary Endpoint Reached in Phase II Prostate Cancer Trial

A first analysis of the primary endpoint based on data from at least six months of treatment of more than 200 patients has been performed in Active Biotech AB's ongoing Phase II clinical study of TASQ in patients with asymptomatic, castrate resistant, metastatic prostate cancer. In this analysis, safety, efficacy, and certain biomarkers were evaluated. The primary endpoint, to show a difference in the number of patients with disease progression at six months, was reached. The fraction of patients with disease progression during the six month period was 43 percent for patients treated with TASQ, compared to 67 percent for placebo-treated patients. The median progression free survival was 24.7 weeks for the TASQ group, compared to 12.9 weeks for the placebo group. TASQ treatment also had a positive effect on several biomarkers relevant for prostate cancer progression and was generally well tolerated. No safety concerns significantly affecting the risk/benefit ratio for TASQ were identified. The top-line data are based on the local review of disease progression and an additional central review is currently ongoing. Complete results from the trial including additional details and data from the central review will be presented at an upcoming scientific conference and in scientific publications. Source: Marketwire 12/14/09

Phase III Study Compares Injectable Treatments for Schizophrenia

Treatment with once-monthly Invega® Sustenna™ is not inferior to treatment with biweekly Risperdal® Consta®, according to new data from a comparative study of both treatments in patients with schizophrenia. Results of the 13-week clinical trial were released in December. The objective of this study was to show that Invega Sustenna, once-monthly injectable atypical antipsychotic that was recently approved in the U.S. for the acute and maintenance treatment of schizophrenia in adults, was statistically similar (noninferior) to Risperdal Consta, a long-acting injectable atypical antipsychotic that is also approved for the treatment of schizophrenia in adults in the U.S., as measured by the Positive and Negative Syndrome Scale (PANSS). The randomized, double-blind, double-dummy trial included 1,220 adults with a diagnosis of schizophrenia and a PANSS total score of 60 to 120. The primary endpoint of the trial was the change in the PANSS total score versus baseline. Noninferiority would be concluded by calculation using a 95 percent confidence interval, based on a prespecified change in total PANSS score. Secondary efficacy measures included change from baseline for Clinical Global Impression-Severity (CGI-S) and Personal and Social Performance (PSP) Scale. Results showed similar improvement in the mean change from baseline to endpoint in PANSS total score for the Invega Sustenna (-18.6) and Risperdal Consta groups (-17.9). Because the lower limit of the 95 percent confidence interval exceeded the prespecified margin of -5, Invega Sustenna was concluded to be noninferior to Risperdal Consta. Patients' CGI-S and PSP figures improved similarly in both groups. The study was sponsored by Johnson & Johnson Pharmaceutical Research and Development, L.L.C. Janssen, a division of Ortho-McNeil-Janssen Pharmaceuticals, Inc., markets both products in the U.S. Source: PRNewswire 12/10/09

Company Initiates Phase IIa Study of Oxygen Therapeutic Agent in Severe Trauma Patients with Hemorrhagic Shock

Sangart, Inc. in December announced the initiation of a dose-finding study designed to evaluate the safety and efficacy of MP4OX treatment plus standard of care in severely injured trauma patients with lactic acidosis due to hemorrhagic shock. MP4OX is a novel oxygen therapeutic agent that is designed to provide rapid oxygen delivery to ischemic tissues. The multicenter, randomized, double-blind, controlled study will enroll up to 75 patients who have suffered hemorrhagic shock with lactic acidosis across approximately 12 trial sites in Europe and South Africa. The primary objective of the study is to measure reduction in lactate levels after infusion of MP4OX. Acute traumatic injury, including both blunt and penetrating trauma, is often associated with severe bleeding that can lead to hemorrhagic shock. During shock, inadequate perfusion of critical organs can lead to insufficient oxygenation of tissues, which can be detected by an increase in lactate levels. Sangart's product platform is based on the MP4 molecule, an investigational biopharmaceutical product designed to enhance the perfusion of oxygen-deprived (ischemic) tissues and provide targeted oxygen delivery in the capillaries. Using a novel pegylation approach, Sangart produces the MP4 molecule designed at the optimal oxygen affinity, diffusion potential, and molecular size to perfuse capillaries and target oxygen delivery to tissues specifically at risk of ischemia. Source: PRNewswire 12/9/09

Drug Shows Positive Responses, Low Side Effects in Multiple Myeloma

The second-generation proteasome inhibitor carfilzomib is showing noteworthy response rates and low levels of adverse side effects among multiple myeloma patients in a Phase II clinical trial, researchers reported in December at the 51st Annual Meeting of the American Society of Hematology. The updated data from the 17-site study focuses on patients with relapsed or resistant multiple myeloma who have received one to three prior therapies, but not the drug bortezomib, the original proteasome inhibitor. While new agents are extending life expectancies for patients with the disease, they often have adverse side effects, including severe neuropathy. Carfilzomib is showing good response rates, with an improved side effects profile. Neuropathy is peripheral nerve pain or numbness that can become debilitating enough to halt treatment. In preclinical studies, carfilzomib has been better tolerated than bortezomib, allowing consecutive day dosing and treatment over extended periods of time. Both drugs work by targeting the cell's proteasome, which destroys mutated or damaged proteins. Blocking this process causes cell death. Carfilzomib targets and binds to the proteasome differently than bortezomib. Researchers previously observed higher response rates to carfilzomib among patients who had never been treated with bortezomib, compared to those with relapsed disease following bortezomib therapy. Fifty-seven bortezomib-naive patients have been enrolled, and 56 have received at least one dose of carfilzomib. Prior therapies included alkylators, stem cell transplant, thalidomide, lenalidimide, and anthracyclines. Patients entered the trial with a variety of side effects from previous treatments, including 21 patients with neuropathy (37 percent) and 12 (21 percent) with impaired renal function. The mean time from diagnosis was four years. Carfilzomib was given intravenously on six days every 28 days for up to 12 cycles. To date, the mean number of doses administered per patient is 30. Five patients have completed the full 12-cycle protocol, and another five have completed at least nine cycles. Seventeen are continuing on in the study. Among 51 evaluable patients, overall response rate has been 45 percent, including one complete response and 18 partial responses. An additional nine patients had minor response, and disease stabilized at least six weeks in 10 patients. This is considered noteworthy for a single-agent drug regimen in patients with tumor progression despite previous therapy with novel combinations. Adverse events, most of which were minor, included fatigue, nausea, and anemia. The incidence of neuropathy dropped to seven cases (12 percent) in 51 evaluable patients. Dose modifications rarely were required. No patients who entered the trial with impaired renal function needed to have their dose reduced due to renal side effects. The clinical trial is funded by Proteolix, the developer of carfilzomib. Source: Newswise 12/7/09

Pivotal Trial Data Demonstrate Device Reduced Seizures in People with Epilepsy

NeuroPace, Inc. in December announced that results from its pivotal trial demonstrated the RNS® System, a novel investigational device that utilizes responsive brain neurostimulation, significantly reduced the frequency of seizures among people who have a common form of epilepsy that is difficult to treat with medication. The pivotal trial data, which were presented at the American Epilepsy Society's 63rd Annual Meeting, included 191 people with medically intractable partial onset epilepsy enrolled at 31 sites located in the United States. The RNS System is designed to continuously monitor brain electrical activity and, after identifying a patient's unique "signature" indicating a seizure is starting, deliver brief and mild electrical stimulations with the intention of suppressing the seizure. NeuroPace plans to submit a premarket approval application to the U.S. Food and Drug Administration in early 2010 seeking approval of the RNS System for the treatment of epilepsy. The trial demonstrated a statistically significant reduction in seizure frequency in the treatment group (responsive stimulation active) as compared to the sham stimulation group (responsive stimulation inactive). During the last two months of the three month blinded evaluation period of the study, people in the treatment group experienced a mean percentage reduction of 29 percent in their disabling seizures, compared to 14 percent reduction for those in the sham stimulation group. In the long-term, open-label period of the trial, at least 12 weeks of data were available for 171 study participants; 47 percent of these subjects experienced a 50 percent or greater reduction in their seizure frequency based on their most recent 12 weeks of data, as compared to their baseline. The trial also demonstrated a serious adverse event rate less than comparative surgical procedures. There were no serious unanticipated device related adverse events reported in the trial. There was no difference between the treatment and sham stimulation groups when comparing the rate of adverse events, including depression, memory impairment, and anxiety. Source: PRNewswire 12/7/09

Phase IIa Data Focuses on Cognitive Impairment in Schizophrenia Patients

Allon Therapeutics Inc. announced in December that the results of a Phase IIa clinical trial presented at a major scientific meeting indicate that the company's lead neuroprotective drug candidate davunetide achieved measurable positive treatment effects in schizophrenia patients with cognitive impairment. The trial was managed by TURNS (Treatment Units for Research on Neurocognition and Schizophrenia), with substantial financial support from the National Institute of Mental Health, part of the U.S. National Institutes of Health. The latest data support and augment top-line results released in July 2009. However, the trial did not achieve statistical significance on the primary endpoint, which was the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) composite battery of tests. Numerical positive treatment effects were seen in specific tests that measured visual learning and working memory. A change was observed in verbal learning favoring placebo. The trial achieved a statistically significant positive treatment effect on a secondary endpoint, which was the University of California at San Diego Performance-based Skills Assessment (UPSA) test. The UPSA scale assesses the functional capacity of skills for daily living and has been recognized by drug regulators as an appropriate coprimary endpoint in patients suffering from schizophrenia-related cognitive impairment. The trial was a randomized, double-blind, placebo-controlled, parallel group study. Two doses of davunetide administered intranasally, 5 mg once daily, and 15 mg twice daily, were compared to placebo. Patients were treated for 12 weeks. All patients were on a stable dose of an approved antipsychotic therapy. A total of 54 patients completed the trial at seven leading medical institutions in the United States. Source: Marketwire 12/7/09

Multiple Myeloma Patients Experience High Response Rate with Three-Drug Combination

A new three-drug combination has shown in a Phase I/II clinical trial that it is a "highly effective regimen" in the treatment of patients newly diagnosed with multiple myeloma, a cancer of white blood cells in bone marrow, say researchers from Dana-Farber Cancer Institute. Partial responses or better were seen in all of the 66 patients treated with the drug combination in the multicenter study, with 74 percent having a "very good partial response rate" in the Phase II population. The rate of complete or "near complete" responses to the therapy was also encouraging at 54 percent. The regimen, known as RVD, combined the drugs Revlimid® (lenalidomide), Velcade® (bortezomib), and dexamethasone, which previously were found to be highly effective in multiple myeloma patients who had relapsed or no longer responded to first-line therapies. Fifteen of the 35 newly diagnosed patients in the open-label Phase II portion of the study subsequently underwent autologous (using their own blood-forming stem cells) transplants, a standard treatment for multiple myeloma. For the entire group, after a median 19.3 months of follow up, the median time-to-progression (TTP) of the disease, progression-free survival (PFS), and overall survival (OS) had not yet been reached. The estimated TTP and PFS at one year are 76 percent, and the estimated one-year overall survival is 100 percent, the results showed. The study's leader says it was "particularly exciting" to observe that the high response rate was not affected by the specific genetic characteristics of the patients' disease. Patients with so-called "adverse cytogenetics" are at higher risk for treatment failure and death, but in the current study, the drug combination worked as well for them as it did in patients with more favorable cytogenetic features. The combination has now gone into large Phase III clinical trials. Source: EurekAlert! 12/5/09

Treatment for Chronic Rhinosinusitis with Nasal Polyps Termed Effective

OptiNose in December announced the publication of results from its Phase II clinical study investigating the efficacy and tolerability of its novel, intranasal drug/device product for the topical treatment of chronic rhinosinusitis with nasal polyps in the journal Rhinology. Chronic rhinosinusitis with nasal polyps is a chronic disease that can significantly reduce a patient's quality of life, causing facial pressure and pain, nasal obstruction, and reduced sense of smell. The OptiNose device delivers drugs to target sites deep in the nose, including the sinus openings where nasal polyps emerge. In the study, patients in the active treatment group experienced highly significant reductions in polyp size compared to placebo with corresponding significant and progressive improvements of all symptom scores, including rhinitis symptoms, nasal discomfort, and sense of smell. At the conclusion of the study, the polyps had disappeared in 10 out of 54 patients in the active group, whereas polyps were still present in all patients in the control group. The multicenter study, conducted in 109 patients with mild-to-moderate bilateral nasal polyposis, assessed the efficacy, safety, and tolerability of 400 micrograms of fluticasone propionate delivered twice daily with OptiNose's liquid nasal drug delivery device over a 12-week period. Source: EurekAlert! 12/1/09

Company Receives Refuse to File Letter from FDA on MS Tablets

EMD Serono, an affiliate of Merck KGaA, Darmstadt, Germany, announced in November that it received a refuse to file letter from the U.S. Food and Drug Administration (FDA) on the New Drug Application (NDA) for Cladribine Tablets, EMD Serono's proprietary investigational oral formulation of cladribine, as a therapy for relapsing forms of multiple sclerosis (MS). EMD Serono plans to request a meeting with the FDA as soon as possible to discuss its comments on the NDA submission and to reach an understanding on what would be required for the NDA to be accepted for review. Cladribine is a small molecule that may interfere with the behavior and the proliferation of certain white blood cells, particularly lymphocytes, which are thought to be involved in the pathological process of MS. The clinical development program for Cladribine Tablets includes two Phase III trials and one Phase II trial. Source: PRNewswire 11/30/09

First Patients Enrolled in Multinational Study for Reduction of Transplant-Related Mortality

Kiadis Pharma announced in November that the first patients have been enrolled in a multinational registration clinical trial with the company’s orphan product, ATIR™, a donor lymphocyte preparation depleted of alloreactive T-cells. The study is designed to show reduction in transplant-related mortality after one year following an allogeneic stem cell transplantation with a mismatched (haplo-identical) donor in blood cancer patients eligible for an allogeneic stem cell transplantation but without having a matched donor available. The study is currently open for enrollment in centers in Europe and Canada and is designed to serve as a registration trial for European approval. ATIR is designed to provide early immune reconstitution to fight infections and remaining tumor cells (by eliminating the use of prophylactic immune suppressants) while preventing acute severe (Grade III/IV) graft versus host disease. Source: PRNewswire 11/30/09

Ibuprofen Injection Demonstrates Significant Fever Reduction in Hospitalized Burn Patients

Cumberland Pharmaceuticals Inc. in November announced positive new top-line results from a study evaluating the safety and efficacy of Caldolor (ibuprofen) Injection in treating fever in hospitalized burn patients. Statistical significance was achieved for the primary endpoint of reducing fever in burn patients over the first 24 hours of treatment. The study evaluated 61 adult burn patients with second or third degree burns covering more than 10 percent total body surface area. Other participant criteria included an anticipated hospital stay of more than 72 hours and temperatures of 38 degrees C (100.4 degrees F) or greater. Patients were administered 800 mg of Caldolor every six hours for five consecutive days. The multicenter, randomized, double-blind, placebo-controlled trial was conducted at five U.S. and international clinical sites, including hospital burn units and burn centers. As with previous clinical trials, Cumberland Pharmaceuticals plans to submit the results of this study for publication as well as for medical meeting presentation. Source: PRNewswire 11/23/09

Phase IIb Clinical Trial in Cystinosis Completed

Raptor Pharmaceutical Corp. in November announced results from a Phase IIb clinical trial of its proprietary delayed-release cysteamine bitartrate (DR Cysteamine) in patients with nephropathic cystinosis. The trial, conducted at the University of California, San Diego General Clinical Research Center, evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of a single dose of DR Cysteamine in nine cystinosis patients. Among other results, the product demonstrated improved tolerability and the potential to reduce total daily dosage and administration frequency compared to immediate-release cysteamine bitartrate; pharmacokinetic evaluation showed that it had a terminal half-life more than three times longer than the terminal half-life of immediate-release cysteamine bitartrate capsules; and twice-daily DR Cysteamine may achieve the same pharmacodynamic result while using a daily dose 30 percent lower than immediate-release cysteamine bitartrate capsules administered four times daily. Raptor plans to meet with the Food and Drug Administration and European Medicines Agency to discuss the results the study and its plans to initiate a repeat-dose, pivotal Phase III trial at multiple sites in the U.S. and Europe in the first quarter of 2010. Source: PRNewswire 11/23/09

Initial Results Announced From Phase IIb/III Study in Pediatric Eosinophilic Esophagitis

Ception Therapeutics, Inc. and Cephalon, Inc. in November announced results from a Phase IIb/III clinical trial for Cinquil™ (reslizumab), an investigational humanized monoclonal antibody against interleukin-5, as a treatment for pediatric eosinophilic esophagitis (EoE). Ception and Cephalon continue to fully analyze the data and are planning to perform an analysis of an ongoing open-label extension study to help further assess the clinical results. The four-month, double-blind, placebo-controlled clinical trial evaluated the efficacy and safety of the product in 226 pediatric patients between five and 18 years of age with poorly controlled EoE. Study participants were randomized to receive one of three dose levels of Cinquil (1 mg/kg, 2 mg/kg, and 3 mg/kg) or placebo. The reduction of esophageal eosinophils was marked in all active groups, with statistically significant reductions of peak esophageal eosinophils at all dose levels compared to placebo. All active groups also experienced improvement in the physician global assessment of their symptoms. However, the placebo cohort also demonstrated improvement in their physician global assessment; therefore, there were no statistically significant differences between the active groups and the placebo group for this endpoint. EoE is a rare disease more frequently diagnosed in children. The symptoms of EoE frequently mimic severe gastroesophageal reflux disease; however, individuals affected by EoE commonly have other allergic diseases such as rhinitis, asthma, and/or eczema. There are no approved therapies for EoE; however, symptoms of the condition are typically treated through use of restricted diets and / or steroids. Source: PRNewswire 11/23/09

Phase II Study of Cat Allergy Therapy Identifies Approach for Late-Stage Development

Circassia Ltd in November announced positive results from a recently completed Phase II clinical study of its ToleroMune® cat allergy therapy, which successfully identified the optimal dosing regimens to progress into late-stage development. The clinical trial, which was the first of its kind in the field of cat allergy immunotherapy, showed that the treatment was extremely well tolerated and greatly reduced sufferers' symptoms. Circassia conducted the double-blind study in Canada, where 121 subjects with confirmed cat allergies were randomized to receive placebo or one of four different treatment regimes with standardized doses of ToleroMune. The volunteers were exposed to cat allergens (aerosolized dander) in an environmental exposure chamber for three hours each day on four consecutive days, both before and after treatment. At set time points, the subjects scored their ocular and nasal symptoms to allow investigators to measure the effect of the treatment. This is the first trial of a cat allergy immunotherapy to use this validated approach. The study's results demonstrate that ToleroMune therapy can dramatically reduce both nasal and ocular allergy symptom levels, and that the treatment effect grows as the duration of exposure increases and symptoms are at their greatest. The optimal regimen decreased total symptom scores by 67 percent compared with placebo. Source: PRNewswire 11/20/09

Pivotal Study Shows Aerosol Spray Increased Ejaculatory Latency

At November’s annual meeting of the Sexual Medicine Society of North America, Inc., Sciele Pharma, Inc., a Shionogi Company, and Plethora Solutions Limited, a wholly owned subsidiary of Plethora Solutions Holdings PLC, presented data from its second positive pivotal study of PSD502 for the treatment of premature ejaculation (PE). Results of the double-blind treatment phase of this study, which enrolled 256 patients from the U.S., Canada, and Poland, are consistent with previously reported results of the pivotal trial conducted in Europe and showed that men who were treated with PSD502 five minutes before intercourse were able to delay ejaculation up to five times longer than those who used placebo. Additionally, patients and partners in both trials reported significant improvements in sexual satisfaction, and the drug was well tolerated. PSD502 is a proprietary formulation of the two marketed drugs lidocaine and prilocaine dispensed by a metered dose aerosol. PSD502 works selectively on non-keratinized skin on the glans penis (head of the penis). Both pivotal trials showed clinically and statistically significant efficacy in the treatment of PE, as measured by changes in intravaginal ejaculatory latency time (IELT) and index of PE (IPE), a patient-reported outcome of ejaculatory control, sexual satisfaction, and distress. Also presented for the first time at the conference were two subset analyses of the European Phase III trial data showing increased ejaculatory latency and improvements in patent-reported outcomes seen in the first month of use with PSD502 were maintained over two to three months of treatment; and a significant positive correlation between mean IELT and IPE domain scores after three months of treatment, indicating that increases in IELT are associated with improvements in patient-reported outcomes. Source: EurekAlert! 11/19/09

Positive Results Seen in Phase IIb Shingles Trial

In November, Epiphany Biosciences announced results from its Phase IIb dose-ranging study of EPB-348 (valomaciclovir) in patients with shingles (herpes zoster) infection. The study's primary endpoint was noninferiority of once-daily valomaciclovir compared to thrice-daily valacyclovir in terms of time to complete crusting of the shingles rash. The double-blinded study enrolled 373 patients who were randomized into three arms: 1 gram of once-daily EPB-348, 2 grams of once-daily EPB-348, and thrice-daily valacyclovir (1 gram, three times per day). Eighteen patients also received 3 grams of once-daily EPB-348. Once-daily EPB-348 at 2 grams met the primary endpoint. EPB-348 was also noninferior to valacyclovir in the secondary endpoints of time to complete pain resolution, time to rash resolution, and time to cessation of new lesion formation. The highest dose of valomaciclovir demonstrated superiority to valacyclovir with regards to the primary endpoint. Dose-dependent trends to improved pain resolution in the subset of treated patients who were over 50 years old and trends to faster resolution of severe pain in patients of all ages were seen in the higher dose EPB-348 treatment arms when compared to valacyclovir. All doses of EPB-348 showed improvement over valacyclovir for patients presenting for first treatment toward the end of the 72-hour treatment window. Currently approved shingles treatments are effective only within the first 72 hours of rash appearance. EPB-348 has also been shown to be effective against acute infectious mononucleosis, for which there is no Food and Drug Administration-approved treatment, in a Phase IIa study. Source: PRNewswire 11/18/09

Erectile Dysfunction Treatment Demonstrates Efficacy in Phase III

VIVUS, Inc. in November announced positive results from REVIVE (TA-301), a Phase III pivotal study evaluating the safety and efficacy of avanafil, an investigational drug candidate for the treatment of erectile dysfunction (ED), in 646 patients. The randomized, double-blind, placebo-controlled efficacy and safety study evaluated three doses of avanafil in men with a history of general ED for at least six years. The study met all primary endpoints across the three doses studied by demonstrating statistically significant improvement in erectile function as measured by the Sexual Encounter Profile and improvements in the International Index of Erectile Function score. The study, conducted under a Special Protocol Assessment with the U.S. Food and Drug Administration (FDA), also demonstrated successful intercourse in 30 minutes or less, and a favorable side-effect and safety profile. Nearly 80 percent of sexual attempts among patients on a 200 mg dose of avanafil had erections sufficient for intercourse; full efficacy was maintained for all doses across multiple time points from 30 minutes to beyond six hours; and all FDA-defined primary endpoints were met across all three doses. REVIVE is the first of four Phase III avanafil trials. Additional studies include treatment in diabetic males with ED (REVIVE-Diabetes, TA-302) and in males with ED following a post-radical prostatectomy (TA-303), each with a treatment period of approximately 16 weeks. In March of this year, VIVUS initiated an open-label safety study (TA-314) evaluating the long-term safety and tolerability of avanafil as part of its path toward a New Drug Application filing with the FDA. TA-314 is being conducted over one year in approximately 600 patients across 40 U.S. centers; patients completing either the 12-week REVIVE or REVIVE-Diabetes studies are eligible to participate in TA-314. Results of the study are expected to be available by late 2010. In total, the Phase III avanafil clinical program will enroll approximately 1,300 patients. Source: PRNewswire 11/18/09

Company Announces Modification to Phase IIb Study of Chronic HCV Infection

InterMune, Inc. in November announced that the ongoing Phase IIb study conducted by Roche of ITMN-191 (RG7227) combined with standard of care (SOC) Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin) in hepatitis C virus (HCV) treatment-naive patients has been modified. The study has four dosage cohorts: SOC, 300 mg q8h plus SOC. 600 mg q12h plus SOC, and 900 mg q12h plus SOC. To date, approximately 175 patients have been enrolled in the study. Three patients in the blinded 900 mg q12h dosage cohort experienced a Grade 4 elevation in ALT levels, one of whom experienced an elevation of total bilirubin while also receiving concomitant allopurinol. After its review of the unblinded data from all cohorts, the study's independent data monitoring committee recommended that the 900 mg q12h cohort be discontinued and that all other cohorts of the study continue. The companies accepted the committee's recommendations. The objective of the randomized, double-blind, placebo-controlled study is to further characterize the safety, tolerability, and antiviral effects of ITMN-191 in triple combination, compared to SOC. The two-part study will evaluate treatment regimens of both 12 and 24 weeks. The second part of the study is designed to further evaluate ITMN-191 in a 24-week triple combination regimen with Pegasys and Copegus. Source: PRNewswire 11/17/09

Trials Initiated for the Treatment of Atrial Fibrillation in Open-Chest Procedures

nContact Surgical, Inc. in November announced the initiation of a clinical trial designed to evaluate the safety and efficacy of its Numeris® - AF Tethered Coagulation System with VisiTrax® device in an open-chest concomitant procedure for the treatment of longstanding persistent atrial fibrillation (AF). This multicenter, nonrandomized, prospective clinical trial will enroll up to 107 participants at 15 study sites across the United States. The procedure involves creating a biatrial lesion pattern on a beating heart to block electrical signals that cause AF. The lesions are created using nContact's tethered device on the upper chambers of the heart, the left and right atria, where the AF occurs. Once the lesions have been created, a cardiothoracic surgeon will be able to confirm intraoperatively through pacing whether the lesions are nonconductive and the pulmonary veins are isolated. The hope is that this study will lead to participants being free from AF and completely off class I and class III antiarrhythmic drugs (AADs) following their treatment. The decision to stop the use of AADs will be decided by each participant's physician evaluation of the participant's medical status. Source: PRNewswire 11/16/09

Phase III Trial in Small Cell Lung Cancer Did Not Meet Primary Endpoint

Poniard Pharmaceuticals, Inc. on November 16 announced that its pivotal Phase III SPEAR (Study of Picoplatin Efficacy After Relapse) trial of picoplatin in the second-line treatment of small cell lung cancer (SCLC) did not meet its primary endpoint of overall survival. The analysis, based on 320 evaluable events (patient deaths), showed a hazard ratio of 0.82 with a p value of 0.089. "We are disappointed that the trial did not meet the primary endpoint. The data indicates that more patients on the best supportive care arm received chemotherapy following progression than those on the picoplatin arm, and we believe that this may have been a significant factor contributing to the trial outcome, as picoplatin appeared to demonstrate a trend toward a survival advantage. Based on these findings and other analyses, we are contacting the [Food and Drug Administration (FDA)] today to request a meeting to discuss a regulatory path forward. We look forward to presenting the full SPEAR efficacy and safety data at an upcoming medical conference early next year," said Jerry McMahon, PhD, chairman and chief executive officer of Poniard. "We believe that the SPEAR data, coupled with efficacy and safety data from more than 1,100 cancer patients treated with picoplatin and the proof-of-concept data from our trials in colorectal, prostate and ovarian cancers, support our continued partnering effort. Our focus will be on the regulatory pathway for picoplatin, partnering activities, and realigning the use of resources for these objectives." The international, multicenter, randomized, controlled trial was conducted under a Special Protocol Assessment with the U.S. Food and Drug Administration (FDA). The trial evaluated the efficacy and safety of picoplatin as second-line therapy in 401 cancer patients with SCLC who were refractory to or who progressed within six months of first-line platinum-based therapy. Picoplatin administered as an intravenous infusion once every three weeks plus best supportive care was compared to best supportive care alone. In addition to the SPEAR trial, Poniard is evaluating intravenous picoplatin in a Phase II clinical trial in patients with colorectal cancer, in a Phase II clinical trial in patients with castration-resistant prostate cancer, and in a Phase I cardiac safety assessment. In addition, final results from a trial of an oral formulation of picoplatin were presented earlier this year. Source: PRNewswire 11/16/09

Viagra for Women? Drug Developed as Antidepressant Effective in Treating Low Libido

The drug flibanserin, which was originally created as an antidepressant, is effective in treating women with low libido, pooled results from three separate clinical trials have found. These trials were the first ever to test a therapy that works at the level of the brain to enhance libido in women reporting low sexual desire. Studies have shown that the prevalence of hypoactive sexual desire disorder in the U.S. ranges from 9 percent to 26 percent of women, depending on age and menopausal status. Flibanserin is currently an investigational drug and is available only to women taking part in clinical trials. The results were presented in November at the Congress of the European Society for Sexual Medicine in Lyon, France. The presentation was given by Elaine E. Jolly, MD, overall principal investigator and a professor at the University of Ottawa in Canada. Jolly and colleagues pooled data from four clinical trials of flibanserin conducted in the U.S., Canada, and Europe. A total of 1,946 premenopausal women ages 18 and older were randomized to receive either flibanserin or placebo for 24 weeks, with four weeks of pre-treatment baseline measurement and four weeks of post-treatment follow-up. Initially, four different dosing regimens were used in the trials: 25 milligrams twice a day, 50 milligrams once a day at bedtime, 50 milligrams twice a day, and 100 milligrams once a day at bedtime. The dosing regimens totaling 50 milligrams a day were not effective, while the regimens totaling 100 milligrams were. So, the results being reported are from only three of the four trials and are based on the 100 milligrams once a day dosing regimen only. The researchers concluded that treatment with 100 milligrams of flibanserin once a day was associated with significant improvements versus placebo in terms of satisfying sexual events, sexual desire, distress associated with sexual dysfunction, and sexual functioning. The trials were funded by Boehringer Ingelheim Pharmaceuticals, the manufacturer of flibanserin. Source: Newswise 11/16/09

Monotherapy Found Effective for GERD Symptoms in Phase IIb Trial

Addex Pharmaceuticals announced in November that it achieved statistically significant efficacy on the primary endpoint, increasing the number of symptom free days in the Phase IIb trial of ADX10059 as a monotherapy in patients with gastroesophageal reflux disease (GERD), the cause of heartburn and other symptoms. ADX10059 is a first-in-class reflux inhibitor that works by reducing activation of the metabotropic glutamate receptor 5 (mGluR5) through negative allosteric modulation (NAM). This approach may lead to a new class of drugs that addresses the causes of GERD rather than just the symptoms. Study ADX10059-204 was a double-blind, placebo-controlled, multicenter European trial in 103 GERD patients known to respond well to proton pump inhibitors (PPIs). There was a two-week baseline symptom evaluation period followed by two weeks of administration of ADX10059 120 mg twice daily. ADX10059 was used as a monotherapy so patients in the study did not use PPIs or other acid suppressant therapy during the baseline and study treatment periods. The primary clinical endpoint was the patient reported number of GERD symptom free days in the second week of treatment compared to the last seven days of baseline. Objective measures of the effects of ADX10059 on esophageal function and reflux events were made in a subset of 24 patients on the day before starting treatment and on the last day of treatment using impedance pH monitoring and esophageal manometry. Reflux events on impedance pH monitoring were the mechanistic primary variables. At baseline, the mean number of symptom free days was 0.46 in the ADX10059 group and 0.72 days in the placebo group. During the second treatment week, this increased to 2.5 days in the ADX10059 group and to 1.71 days in the placebo group. In the subset of 24 patients who underwent mechanistic monitoring, ADX10059 also achieved statistical significance in two mechanistic primary endpoints. ADX10059 significantly reduced total impedance measured reflux events and also acidic reflux events over the 24-hour monitoring period. ADX10059 also showed statistical superiority over placebo for a variety of secondary variables, including an increase in heartburn free days, a reduction in sleep disturbance, a reduction in the requirement for antacid medication, and an improvement in a GERD symptom patient-reported outcome questionnaire. Addex also announced that enrollment has been completed in the second trial of ADX10059 in GERD patients. In the study ADX10059-205, the product is being used as an add-on therapy in patients who are partial responders to PPIs. Results are expected in January 2010. A third trial, where ADX10059 is being studied as a migraine prophylaxis in patients with frequent migraines, is progressing as expected and data will be reported in the second quarter of 2010. Source: Marketwire 11/16/09

Phase III Data Show Drug Significantly Improves Patient Outcomes Following PCI

The Medicines Company announced in November that the data from 13,941 patients treated in the discontinued CHAMPION Phase III program of cangrelor did not show superiority to 600 mg clopidogrel given orally for the prespecified primary endpoint comprising death, myocardial infarction (MI), or ischemia driven revascularization (IDR) at 48 hours. However, full analysis of the CHAMPION program data revealed strong evidence of pharmacological effects, clinical effectiveness, and suitable safety in patients undergoing percutaneous coronary intervention (PCI). In fact, cangrelor significantly reduced the composite endpoint of death, Q-wave MI, and IDR. Two separate presentations on the results of the CHAMPION PCI and CHAMPION PLATFORM trials were given at the American Heart Association Scientific Sessions 2009 in Orlando, Fla. by the lead authors of two papers on these results published in the New England Journal of Medicine. CHAMPION program data were analyzed after the program's discontinuation in May 2009 when 98 percent of targeted patients in CHAMPION PCI and 84 percent in CHAMPION PLATFORM had been enrolled. At that time, the program's independent interim analysis review committee reported to the company and the principal investigators that the CHAMPION PLATFORM trial was not expected to meet its primary endpoints. Cangrelor was superior to clopidogrel (600 mg given orally before PCI) in inhibiting platelet aggregation measured by a range of laboratory tests during the first two hours of treatment, resulting in more rapid and greater effect than that of clopidogrel. The antiplatelet effects of cangrelor are quickly reversible, enabling smooth transition to oral clopidogrel with no evidence of attenuation of clopidogrel effect. The risk of the composite endpoint of death, Q-wave MI, or IDR was 39 percent lower on cangrelor than on 600 mg clopidogrel given immediately before or immediately after PCI. Similarly, the risk of the composite endpoint of death, Q-wave MI, or stent thrombosis was 45 percent lower. In CHAMPION PCI, cangrelor was not superior to 600 mg clopidogrel loading dose in the 37 percent of patients who entered the trial on clopidogrel maintenance therapy. However, cangrelor was superior to a 600 mg clopidogrel loading dose in remaining 63 percent thienopyridine-naïve patients with a relative risk reduction for death/Q-MI/IDR of 43 percent. In CHAMPION PLATFORM, all patients were thienopyridine-naïve and cangrelor showed a relative risk reduction for death/Q-MI/IDR of 45 percent. The company will continue enrolment in the BRIDGE study--a trial testing cangrelor as a platelet inhibitor in patients with coronary stents who need to discontinue clopidogrel prior to planned surgery. The company also will initiate various other clinical pharmacology studies. Source: Marketwire 11/15/09

Phase I Study Initiated for Dyslipidemia Treatment

Esperion Therapeutics in November announced that the company has initiated a Phase I clinical study for ETC-1002, the company's novel small molecule compound designed to beneficially regulate the levels of plasma lipids and lipoproteins. The single escalating dose study in healthy volunteers will be the first clinical study conducted by Esperion since the reestablishment of the company in May 2008. ETC-1002 is being developed to treat dyslipidemia, an early-stage risk factor of coronary artery disease and associated metabolic syndromes. The compound targets lipid metabolism in two ways: first, by inhibiting fatty acid and cholesterol synthesis, and second, by enhancing oxidation of fatty acids. ETC-1002 therefore has the potential to lower LDL-C and triglycerides and also to increase HDL-C. Source: PRNewswire 11/13/09

Phase II Results Promising for Nonconstipating IBS Drug

Lexicon Pharmaceuticals, Inc. announced in November that the company's investigational new drug, LX1031, a tryptophan hydroxylase (TPH) inhibitor, demonstrated positive results in clinically important parameters for the treatment of nonconstipating irritable bowel syndrome (IBS). Top-line results showed that treatment with one gram of LX1031 four times daily produced a statistically significant improvement in global assessment of relief of IBS pain and discomfort over the four-week dosing period as compared to placebo. Improvements in global assessment parameters also corresponded with statistically significant improvements in stool consistency. Notably, increased clinical response correlated with a greater reduction in serotonin synthesis as reflected by measures of urinary 5-HIAA, a breakdown product of serotonin. The Phase II clinical trial, which began at the end of December 2008, was a four-week, randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of LX1031 and its effects on symptoms associated with IBS. The study included 155 patients with either diarrhea-predominant IBS or mixed IBS. Two dose levels were evaluated: a 250 mg dose and a 1,000 mg dose, each administered four times daily. LX1031 was well tolerated, with no statistically significant differences in adverse events observed between placebo and either treatment group. Efficacy endpoints evaluated included a global assessment of adequate relief, as well as measures of specific symptoms associated with IBS. Based on the positive data obtained, Lexicon intends to pursue the development of LX1031 as a novel treatment for patients with IBS. Top-line results from this study will be presented at the GASTRO 2009 conference in London on November 25. Lexicon has three additional drug candidates progressing through Phase II clinical trials, including LX1032, a peripherally available TPH inhibitor for carcinoid syndrome, LX2931, an S1P lyase inhibitor for rheumatoid arthritis, and LX4211, an SGLT2 inhibitor for Type 2 diabetes. Results from these programs are expected over the next 12 months. Source: PRNewswire 11/12/09

NHLBI Stops Enrollment in Study on Resuscitation Methods for Cardiac Arrest

Enrollment has ended early in a large, multicenter clinical trial comparing two distinct resuscitation strategies delivered by emergency medical service (EMS) providers to increase blood flow during cardiac arrest. The study's independent monitoring board and the National Heart, Lung, and Blood Institute (NHLBI), the lead sponsor of the study, stopped enrollment based on preliminary data suggesting that neither strategy significantly improved survival. One strategy compared different durations of manual cardiopulmonary resuscitation (CPR) by EMS providers before they assessed whether defibrillation was needed, and the other strategy tested the potential benefits and risks of an investigational device to maintain pressure in the chest during CPR. After reviewing data on approximately 11,500 study participants, the study's data and safety monitoring board (DSMB) recommended on October 23 that the NHLBI stop enrollment because sufficient data had been gathered, and continuing recruitment was unlikely to change the overall outcomes of the study. The board had no concerns about the safety of any of the interventions tested, and NHLBI accepted the DSMB recommendations on the same day. Researchers will continue to monitor study participants who agree to follow-up visits for up to six months. They will analyze and publish the final data in the coming months. The NHLBI is part of the National Institutes of Health. Source: NIH press release 11/6/09

Phase III Trials Initiated for Erectile Dysfunction Drug

Dong-A PharmTech Co. Ltd. in November announced that its U.S. partner, Warner Chilcott plc, has initiated two Phase III trials for udenafil, a new long-acting drug under development for erectile dysfunction (ED). Each randomized, double-blind, placebo-controlled trial is designed to evaluate the safety and efficacy of udenafil, an orally administered selective inhibitor of phosphodiesterase, versus placebo. The trials will be conducted in 80 sites in the U.S. and will enroll approximately 1,120 subjects with ED. The company aims to complete the remaining clinical trials for the ED program in the U.S., European Union, and most other major markets within two years. In addition, based on recent positive meetings with the U.S. Food and Drug Administration, it anticipates initiating Phase IIb trials to evaluate the safety and efficacy of udenafil for benign prostatic hyperplasia and pulmonary arterial hypertension. Source: PRNewswire 11/4/09

World's Largest Malaria Vaccine Trial Under Way in Seven African Countries

A pivotal efficacy trial of RTS,S, the world's most clinically advanced malaria vaccine candidate, is now under way in seven African countries: Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and Tanzania. The trial, which is expected to involve up to 16,000 children, is on schedule, with more than 5,000 children already enrolled, researchers announced November 3 at the 5th Multilateral Initiative on Malaria Pan-African Malaria Conference. GlaxoSmithKline Biologicals' RTS,S is the first malaria vaccine candidate to demonstrate significant efficacy during early development to warrant Phase III testing. It is the leading vaccine candidate in the global effort by the PATH Malaria Vaccine Initiative to develop a malaria vaccine. RTS,S is the first vaccine designed primarily for use in Africa. Recent Phase II studies showed that RTS,S reduced clinical episodes of malaria by 53 percent over an eight-month follow-up period. The Phase III trial will evaluate the vaccine's efficacy in two groups of children. One group, aged 6 to 12 weeks, will be vaccinated as part of their regular schedule of infant immunizations; the second group includes children aged 5 to 17 months. The vaccine profile is intended primarily for infants, as they and children under the age of five are the most vulnerable to malaria. Source: EurekAlert! 11/3/09

Patient Enrollment Completed for Phase IIb Trial in Uncontrolled Asthma

Aerovance Inc. in November announced it has completed patient enrollment in a Phase IIb clinical trial of the inhaled dry powder formulation of Aerovant for the treatment of uncontrolled asthma. Top-line results are expected by the second quarter of 2010. Named AeroTrial™, the study enrolled approximately 540 patients at 75 sites in the United States and Europe. In the double-blind, randomized, placebo-controlled, dose-ranging trial, patients with moderate to severe asthma who were inadequately controlled on the combination of inhaled corticosteroids (ICS) and long-acting beta agonists (LABA) were assigned to receive one of three Aerovant doses (1 mg, 3 mg, or 10 mg) or placebo by inhalation twice daily for 12 weeks. During this time the standard ICS and LABA therapies were withdrawn gradually. The trial's primary endpoint is the incidence of asthma exacerbations on Aerovant therapy as compared to placebo. Secondary endpoints include pulmonary function, time to exacerbation, daily peak expiratory flow and symptom scores, immunoglobulin E levels, and fractional concentration of expired nitric oxide. The company anticipates completing dosing of all patients in early 2010 and expects top-line data to be available by the second quarter of 2010. Aerovant is a recombinant human IL-4 variant that is a potent inhibitor of both IL-4 and IL-13 activity. Source: PRNewswire 11/3/09

Initial Results Show Strong Response in Pregnant Women to 2009 H1N1 Vaccine

Healthy pregnant women mount a robust immune response following just one dose of 2009 H1N1 influenza vaccine, according to initial results from an ongoing clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health. A preliminary analysis of blood samples taken 21 days postvaccination from a subgroup of 50 pregnant women participating in the trial shows that in 25 women who received a single 15-microgram dose of the vaccine, the H1N1 flu vaccine elicited an immune response likely to be protective in 92 percent of these women; and in 25 women who received a single 30-microgram dose of the vaccine, the H1N1 flu vaccine elicited an immune response likely to be protective in 96 percent of these women. The trial began on September 9 and reached its target enrollment of 120 volunteers in mid-October. All participants are between 18 to 39 years old and began the study in their second or third trimester (14 to 34 weeks) of pregnancy. For the overall trial, two injections of vaccine are spaced three weeks apart. Safety is being monitored closely in the trial by the study investigators and by an independent safety monitoring committee. To date, the vaccine appears to be well-tolerated, and no safety concerns related to the vaccine have arisen. The vaccine used in this clinical trial was manufactured by Sanofi Pasteur. NIAID is conducting this trial through five clinical sites affiliated with its longstanding clinical trials network, known as the Vaccine and Treatment Evaluation Units. Source: EurekAlert! 11/2/09

Clinical Tests Begin on Medication to Correct Fragile X Defect

National Institutes of Health-supported scientists at Seaside Therapeutics are beginning a clinical trial of a potential medication designed to correct a central neurochemical defect underlying Fragile X syndrome, the most common inherited cause of intellectual disability. There has to date been no medication that could alter the disorder's neurologic abnormalities. The work is the outcome of basic research that traced how an error in the Fragile X mental retardation (FMR1) gene leads to changes in brain synapses. The changes in turn appear to be the mechanism for learning deficits in Fragile X syndrome. The new trial tests Seaside Therapeutics'novel compound, STX107, which targets the synaptic defect. The National Institute of Mental Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Neurological Disorders and Strokes have provided grant support. Private foundations providing funding include the advocacy groups Autism Speaks and FRAXA Research Foundation. Normally, the protein product of the FMR1 gene acts to dampen the synthesis of proteins at synapses that are stimulated via a specific class of receptors on brain cells--metabotropic glutamate receptors (mGluRs). Without the brake provided by FMR protein, synaptic protein synthesis is excessive and connections do not develop normally. The current study will focus on a compound, designated STX107, that selectively inhibits one type of mGluR receptor, mGluR5. Evidence in mice with Fragile X-like symptoms suggests that reducing levels of mGluR5 can restore normal synaptic protein synthesis and improve function. The initial Phase I study of STX107 will involve healthy volunteers. If results suggest that the medication is safe and tolerable, the study will progress to a Phase II test of dosage and efficacy in adults with Fragile X syndrome. If STX107 shows promise in adults, the compound will be assessed for pediatric safety (with funding from the Best Pharmaceuticals for Children Act through NICHD) prior to initiating clinical trials in children. Source: EurekAlert! 11/2/09

Allergy Immunotherapy Tablet Meets Primary Endpoint Against Grass Pollen

Schering-Plough Corp. in November announced that its investigational sublingual Grass (Phleum Pratense) Allergy Immunotherapy Tablet (AIT) has met the primary endpoint in a U.S. Phase III study of adult subjects in the U.S. with a history of grass pollen induced rhinoconjunctivitis with or without asthma. The investigational Grass AIT treatment is designed to work by inducing a protective immune response against grass pollen allergy and providing sustained prevention of allergy symptoms, treating both the symptoms and the underlying cause of the disease. The multicenter, randomized, placebo-controlled, double-blind, parallel-group clinical trial evaluated the efficacy of the grass sublingual tablet versus placebo in the treatment of grass pollen-induced rhinoconjunctivitis based on the combined (sum of) rhinoconjunctivitis daily symptom score and rhinoconjunctivitis daily medication score averaged over the entire grass pollen season. In the study, 439 adults were randomized to receive either placebo or grass tablet. The study met its primary endpoint. Additionally, the adverse events experienced by subjects receiving the drug in this study were similar to previous studies in adults and include oral itching, with no new or unexpected findings. These data are planned to be submitted for presentation at a U.S. medical conference in 2010. Source: PRNewswire 11/2/09

Company to Initiate Trial of Once-Daily Tablet for Alzheimer's Disease

Adeona Pharmaceuticals, Inc. in November announced that it has received institutional review board approval to initiate a 60-patient, randomized, double-blind, placebo-controlled clinical trial of its patent pending Zinthionein™ ZC-GS150 in an Alzheimer's disease and mild cognitive impairment patient group. The CopperProof 2 trial will test, for the first time, the effects of a novel gastro-retentive, sustained release zinc/cysteine combination tablet on the amelioration of subclinical zinc deficiency, and elevated percentage serum free copper, associated with Alzheimer's disease. Near-term comparative data will be generated and made available in the first part of the study and randomized blinded clinical parameters will also be evaluated in the second part of the study following six months of treatment with Zinthionein ZC-GS150 versus placebo. Adeona believes that Zinthionein ZC-GS150 demonstrates significantly improved bioavailability and tolerability for the patient, which would permit the convenience of once-a-day dosing. Zinthionein ZC-GS150 is intended to be marketed as a medical food for the dietary management of Alzheimer's disease and mild cognitive impairment and available by a physician prescription, with use under medical supervision. Source: Marketwire 11/2/09

Tolerability and Effectiveness Results Reported from ADHD Study

Shire plc in late October announced findings at a major medical meeting from a Phase IIIb study of the tolerability and effectiveness of Daytrana® (methylphenidate transdermal system) in adolescents aged 13 to 17 years diagnosed with attention-deficit/hyperactivity disorder (ADHD). In addition, data regarding the pharmacokinetic profile of Daytrana in children and adolescents were presented. Daytrana, the first and only patch for the treatment of ADHD, is indicated for use in children aged 6 to 12 years with the disorder. The six-month, open-label adolescent extension study found that most adverse events were generally mild to moderate in intensity. Additionally, Daytrana treatment resulted in significant improvements in ADHD Rating Scale IV mean total scores from baseline to end point. Participants were titrated to their optimal dose over five weeks and were then maintained on that dose for an additional five months. Participants from a previous double-blind, seven-week study were able to enroll. In the seven-week study, Daytrana was shown to significantly improve ADHD symptoms as rated by clinicians and parents compared to placebo. The long-term extension study evaluated four doses of the Daytrana patch worn for nine hours at alternating hips and used for about six months. Source: PRNewswire 10/30/09

Global Phase III Study Finds Breast Cancer Treatment Meets Primary Endpoint of Overall Survival

Eisai Inc. in late October announced preliminary results from a recently completed Phase III study with eribulin mesylate (E7389), discovered and developed by the company, in patients with locally advanced or metastatic breast cancer. The global EMBRACE (Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389) study was an open-label, randomized, parallel two-arm, multicenter trial of 762 women with locally recurrent or metastatic breast cancer previously treated with at least two and a maximum of five prior chemotherapy regimens, including an anthracycline and a taxane. The patients were treated either with eribulin (administered intravenously over two to five minutes on days 1 and 8 every 21 days) or with treatment of physician's choice. Treatment of physician's choice is defined as any single agent chemotherapy, hormonal treatment, or biological therapy approved for the treatment of cancer; or palliative treatment or radiotherapy administered according to local practice. Preliminary results from the study demonstrated a statistically significant improvement in overall survival, the primary endpoint, in eribulin-treated patients compared to the physician's choice of therapy. The safety profile of eribulin in this study was consistent with the adverse events seen in previous Phase II clinical studies, and the most common adverse event reported was myelosuppression. Eisai will complete a more detailed analysis of the data prior to submitting marketing authorization applications for eribulin to health authorities in Japan, the United States, and Europe for locally advanced and metastatic breast cancer by the end of the fiscal year 2009. Eisai is currently conducting clinical trials of this compound in-house to evaluate its efficacy and safety not only in breast cancer, but also in non-small cell lung cancer (NSCLC), hormone refractory prostate cancer, and sarcoma. Eisai also includes eribulin as one of the compounds in codevelopment projects based on a strategic collaboration agreement with Quintiles, and will proceed with joint clinical development of this compound for NSCLC and bladder cancer. Source: PRNewswire 10/30/09

NIH Launches Multicenter Trial of Blood Pressure Strategy

The National Institutes of Health (NIH) is launching a large multicenter randomized clinical trial to determine whether maintaining blood pressure levels lower than current recommendations further reduces the risk of cardiovascular and kidney diseases, or age-related cognitive decline. Called the Systolic Blood Pressure Intervention Trial (SPRINT), the nine-year, $114 million study will be conducted in more than 80 clinical sites across the United States. SPRINT will evaluate the potential benefits of maintaining systolic blood pressure at less than 120 mm Hg for adults who are at risk for heart disease or kidney disease. The study will also assess possible risks of this therapeutic strategy. Study participants will be treated with commonly available blood pressure medications to achieve one of two different levels of blood pressure control--either less than 140 mm Hg (standard group) or less than 120 mm Hg (treatment group). Those in the treatment group will take an average of three to four medications; those in the standard group will take about two medications. SPRINT participants will be seen in clinics every few months at the beginning of the study and less frequently as their blood pressure is controlled. The study will include standard tests for determining the health of the heart, kidneys, and brain. The clinical trial is based in large part on observational studies that suggest that maintaining a lower blood pressure level than is currently recommended reduces the risk of cardiovascular diseases. SPRINT will enroll approximately 7,500 participants age 55 years or older with systolic blood pressure of 130 mm Hg or higher. Participants will have a history of cardiovascular disease; be at high risk for heart disease by having at least one additional risk factor, such as smoking or high blood cholesterol levels; or have chronic kidney disease. Enrollment for SPRINT is expected to begin in fall 2010. Source: EurekAlert! 10/29/09

Positive Results Announced on GI Safety of Prodrug for Treating Arthritic Conditions

Logical Therapeutics, Inc. announced in October the positive results of a Phase I/II clinical trial evaluating the gastrointestinal (GI) safety of its investigational drug LT-NS001, the first of a new class of bioactivated prodrugs being developed for the chronic treatment of arthritic conditions. In the study, subjects receiving LT-NS001 experienced a 78 percent reduction in the rate of gastric ulcers, and fewer gastric and duodenal erosions, when compared to subjects receiving Naprosyn® (naproxen). The LT-NS001 prodrug is unique among nonsteroidal anti-inflammatory drugs (NSAIDs) as it is pharmacologically inactive as a COX inhibitor in the GI tract, but once absorbed into the bloodstream, it is converted rapidly to naproxen. LT-NS001 has been engineered to reduce the GI safety risks associated with NSAIDs. In this study, 120 normal volunteers aged 45 to 70 years received either LT-NS001 (n=61) or Naprosyn (n=59) for seven days and underwent an upper GI endoscopy at baseline and on the seventh day to visualize the extent of GI injury. At the conclusion of the study, nine subjects (15.8 percent) had developed a total of 29 gastric ulcers while taking naproxen, compared to only two subjects (3.3 percent) developing three ulcers on LT-NS001. Additionally, subjects receiving LT-NS001 developed no duodenal ulcers. The primary endpoint for the trial, total modified gastroduodenal Lanza score (an indicator of GI injury) demonstrated less overall GI mucosal injury in the LT-NS001 subjects as compared to subjects receiving naproxen. Treatment emergent adverse events also favored LT-NS001 with no serious or severe adverse events, including fewer incidences of abdominal pain, gastritis, and dyspepsia. Source: PRNewswire 10/27/09

Treatment for Primary Biliary Cirrhosis Does Well in Phase II

Intercept Pharmaceuticals, Inc. in October announced positive results from a 165-patient, placebo-controlled, double-blind Phase II clinical trial of INT-747 in patients at more than 30 centers in eight countries with primary biliary cirrhosis (PBC). The study evaluated the effects of adding one of three doses of INT-747 or placebo to ursodeoxycholic acid (UDCA) therapy in patients who did not respond adequately to UDCA therapy alone. All three doses of INT-747 added to UDCA produced a statistically highly significant reduction in alkaline phosphatase (Alk Phos) levels, the primary endpoint at the end of the 12-week treatment period, as compared to patients receiving placebo and UDCA. Alk Phos is a liver enzyme routinely used to evaluate the clinical status and disease progression of PBC patients. All the INT-747 doses added to UDCA produced 20 percent or greater reductions in Alk Phos, with similar significant falls in other clinical liver enzymes. With the exception of a higher incidence of pruritus (itching) in the two top INT-747 dose groups, adverse events were generally similar across all groups. PBC is a chronic autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts within the liver, which may lead to liver failure and the need for liver transplantation. PBC primarily afflicts women with up to 300,000 patients estimated worldwide. According to the company, the performance of INT-747 in this study, together with the previously announced positive Phase II study results in type 2 diabetes patients with nonalcoholic fatty liver disease, supports INT-747's potential as a novel therapeutic across a range of chronic liver diseases. Intercept intends to present the complete data set from the study at an appropriate scientific meeting in 2010. Source: PRNewswire 10/27/09

Company Receives Approval to Begin Trials of Surgical Adhesive in Europe

Cohera Medical, Inc. announced in October that it has received approval to begin human clinical trials of its lead product TissuGlu® in Germany. Receipt of the approval allows the company to proceed with patient recruitment and initiation of an investigational study of its novel internal surgical adhesive, being developed for its first intended use to adhere surgical tissues together in large flap surgeries. The feasibility study will investigate the safety and preliminary effectiveness of TissuGlu and its effect on wound drainage and associated complications in abdominoplasty (tummytuck) surgeries. The study will be conducted at three sites near Bonn, Frankfurt, and Freiburg in Germany and will enroll 40 patients. Patient recruitment is expected to begin in November this year. Source: PRNewswire 10/23/09

Positive Results Seen in Phase II Study of Product for Sedation, Anxiolysis, and Analgesia

AcelRx Pharmaceuticals, Inc. in October announced positive results from a Phase II clinical trial of ARX-03, a proprietary sublingual dosage form combining an opioid, sufentanil, with a benzodiazepine, triazolam. ARX-03 is designed to address the current unmet need for a noninvasive product to provide mild sedation, anxiolysis, and analgesia with rapid onset of action for the increasing number of painful and anxiety-producing office-based procedures. The objective of this randomized, double-blind, placebo-controlled study was assessment of safety, tolerability, and efficacy of ARX-03 relative to placebo in patients undergoing an elective low-volume abdominal liposuction procedure. In the study, 40 patients were randomized to receive either a single sublingual dose of ARX-03 (sufentanil 15 mcg/triazolam 200 mcg NanoTab™) or placebo prior to the injection of a local anesthetic and the subsequent liposuction procedure. Source: PRNewswire 10/22/09

Trial to Focus on Control of Pregnancy Weight in Obese Women

More than half of women in the United States are overweight or obese when they become pregnant, and most go on to gain more than the recommended amount during pregnancy. The excess weight can lead to a myriad of complications, including preeclampsia, diabetes, bigger babies, C-sections, birth injuries, and weight retention after pregnancy. In order to reduce these complications, Kaiser Permanente is launching the first clinical trial to help obese women control their weight during pregnancy. The "Healthy Moms" study, funded by a $2.2 million grant from the National Institute of Child Health and Human Development, began recruiting in October. The trial will enroll 180 obese pregnant women from Washington and Oregon who are members of the Kaiser Permanente health plan; half will receive one-time dietary and exercise advice and the other half will attend two individual counseling sessions and then weekly group counseling for the remainder of their pregnancy. The study will recruit women for 18 months, and preliminary results are expected in three years. Source: EurekAlert! 10/21/09

Investigational CML Drug Meets Primary Endpoint in Pivotal Trial Against Approved Product

Novartis announced in October that Tasigna® (nilotinib) 200 mg met its primary endpoint in the first head-to-head comparison with the company's groundbreaking drug Gleevec® (imatinib mesylate). Tasigna produced faster and deeper responses than Gleevec when given as first-line therapy for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase. Tasigna was well tolerated in the study. The Phase III clinical trial, Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients (ENESTnd), is the largest global randomized comparison of two oral therapies ever conducted in newly diagnosed Ph+ CML patients. Designed to detect a difference in major molecular response between Tasigna and Gleevec after 12 months of treatment, it is also the first registration study in which molecular traces of a key biomarker specific to Ph+ CML have been used as a primary endpoint for regulatory review. The comparison study also met its secondary endpoint, a difference in complete cytogenetic response in favor of Tasigna. ENESTnd is being conducted at 220 global sites, with 846 patients enrolled. Source: PRNewswire 10/20/09

Phase IIb Re-Treatment Study in Rheumatoid Arthritis Goes Well

Trubion Pharmaceuticals, Inc. in October today announced favorable safety and efficacy data following administration of a second course of re-treatment with 800 mg of TRU-015 for rheumatoid arthritis (RA). These data are the latest results from the ongoing open-label re-treatment portion of the Phase IIb (15002) RA study of TRU-015. Pfizer Inc. and Trubion are collaborating on the development of TRU-015 for the treatment of autoimmune and inflammatory diseases, including RA. The new data demonstrate that repeat administration with TRU-015 is generally well-tolerated and results in sustained improvement in the signs and symptoms of RA. The double-blind, placebo-controlled, randomized study is designed to evaluate the safety, tolerability, pharmacodynamics, pharmacokinetics, and clinical activity of repeat doses of TRU-015. Of the 276 original patients who began the study, 240 (204 of whom were rheumatoid-factor positive) entered the first open-label re-treatment portion of the trial. A total of 226 patients from the first re-treatment were enrolled in the second re-treatment portion of the trial. Source: PRNewswire 10/19/09

Phase I/II Brain Cancer Studies Find Drug Crosses the Blood-Brain Barrier

Angiochem, Inc. announced in October that its lead drug candidate, ANG1005, has demonstrated a favorable safety and efficacy profile in more than 100 patients with brain cancer from two separate Phase I/II clinical studies in patients with progressive gliomas, including recurrent glioblastoma, and in patients with progressive brain metastases. In a recently completed brain metastases trial, more than 70 percent of patients receiving therapeutic doses experienced disease control (stable disease or better), with more than half of them showing clear reduction in tumor size. Furthermore, 78 percent of patients with taxane-resistant tumors showed responses, indicating ANG1005 has the potential to be effective against resistant tumors. Of significance, therapeutic doses of ANG1005 were present in patient brain tumor samples, indicating that the drug successfully crosses the blood-brain barrier and concentrates in the tumor, without showing central nervous system toxicity or immunogenicity. Similar trends in patient responses have been observed to date in an ongoing recurrent glioblastoma trial, with approximately 65 percent of patients experiencing disease control. Source: EurekAlert! 10/18/09

Drug Could Provide First Treatment for Scleroderma

Investigators in October said that Gleevec, a drug that is currently approved to treat certain types of cancer, could provide the first treatment for scleroderma, a chronic connective tissue disease for which a treatment has remained elusive. Investigators at Hospital for Special Surgery in New York City enrolled 30 patients with diffuse scleroderma, a widespread severe form of the disease, and gave them 400 mg of Gleevec per day. Patients were evaluated monthly for 12 months during treatment and were seen for follow-up three months after discontinuing the drug. The investigators reported an interim analysis of their results, although the study is ongoing. At one year, the investigators saw a 23 percent improvement in skin scores. The researchers also saw an improvement in forced vital capacity scores by 9.6 percent and diffusion capacity scores by 11 percent in the 18 patients who had completed one year of treatment. The study is the largest single-center trial of Gleevec in scleroderma to date, with the longest duration of treatment and follow-up. Source: EurekAlert! 10/17/09

Gel for Diabetic Foot Ulcers Will Move to Phase III

Cardium Therapeutics in October reported positive data from its Matrix Phase IIb clinical trial of Excellarate™ for the potential treatment of patients with chronic nonhealing diabetic foot ulcers based on the company's Gene Activated Matrix (GAM) technology platform. The study evaluated patients treated with the Excellarate product candidate (GAM501, which is a combination of Ad5PDGF-B and 2.6 percent collagen) or 2.6 percent collagen alone (matrix), compared to patients who received only the protocol-specified standard of care without any applied Ad5PDGF-B or collagen matrix. The study was abbreviated and enrollment ended early after key efficacy measures among blinded groups were observed at rates substantially higher than those expected for patients receiving only standard of care. Nearly half of patients (48 percent) receiving a one-time Excellarate treatment had complete wound closure by 12 weeks, compared to a 31 percent wound closure rate for standard of care. Following completion of safety and preliminary efficacy data, the company plans to schedule a meeting with the Food and Drug Administration to review the complete integrated data set and outline plans for a Phase III clinical study program. Source: PRNewswire 10/14/09

All Endpoints Achieved in Metastatic Pancreatic Cancer Study

Epeius Biotechnologies has confirmed what it calls "the first real breakthrough for pancreatic cancer seen in years," and published a report of tumor-targeted Rexin-G as standalone therapy in chemotherapy-resistant pancreatic cancer. Following Phase I studies at the Mayo Clinic, which affirmed the general safety of Rexin-G, advanced U.S. Phase I/II studies were undertaken, which included a Phase II efficacy component and examined progressive dose escalations of Rexin-G, while monitoring objective tumor responses in a comprehensive manner. Employing these higher doses of Rexin-G led to improved tumor responses, as assessed by all available measures, and nearly tripled the expected survival time, all in a dose-dependent manner. Moreover, this U.S. study serves to establish a critical pharmacological threshold of bioactivity for this otherwise intractable disease, by demonstrating an increase in overall survival time from virtually nil using low doses to more than 28 percent of the patients using high doses surviving beyond one year. The drug met all primary and secondary study endpoints of safety and efficacy by achieving both progression-free survival and overall survival benefits, while avoiding untoward systemic or dose-limiting toxicities. Source: PRNewswire 10/14/09

Interim Phase IIa Data Look Promising in Nonalcoholic Steatohepatitis

Raptor Pharmaceutical Corp. has announced positive findings from the completed treatment phase of its open-label Phase IIa clinical trial of delayed-release cysteamine bitartrate (DR Cysteamine) in adolescent patients with nonalcoholic steatohepatitis (NASH), a progressive form of liver disease. At the completion of the initial six-month treatment phase, the study achieved the primary endpoint: mean blood levels of alanine aminotransferase (ALT), a common biomarker for NASH, were reduced by more than 50 percent. Additionally, more than half of the study participants had achieved normalized ALT levels by the end of the treatment phase. The trial currently has enrolled 11 NASH patients between 11 and 18 years old. Trial subjects continue to be monitored during the six-month post-treatment period currently under way. Full results are being submitted for peer review by Raptor and its study partner, the University of California, San Diego, and are expected to be presented in 2010. Source: PRNewswire 10/12/09

Delayed-Release Capsules Improve Fat Absorption in Patients With Cystic Fibrosis

Solvay Pharmaceuticals, Inc. announced in October that Phase III data published in the Journal of Cystic Fibrosis showed that Creon® (pancrelipase) Delayed-Release Capsules, a pancreatic enzyme replacement therapy, significantly improve a key measure of fat absorption in patients with cystic fibrosis (CF) who suffer from exocrine pancreatic insufficiency (EPI). EPI is a condition resulting from a deficiency in the production and/or secretion of pancreatic enzymes that are necessary to digest nutrients in food and, if untreated, can lead to poor growth, poor weight gain, and failure to thrive in children with CF. According to the study results, patients with CF and confirmed EPI had an improved coefficient of fat absorption (CFA) during treatment with Creon compared to treatment with placebo. Based on the results of this study, Creon was approved by the Food and Drug Administration with an indication to treat EPI due to CF or other conditions. In the double-blind, randomized, placebo-controlled, two-arm, crossover study, CFA was greater during treatment with Creon (88.6 percent) compared to placebo (49.6 percent). Source: PRNewswire 10/9/09

Multicenter Clinical Study Completed for Imaging Prostate Abnormalities

ProUroCare Medical, Inc. in October announced the completion of a National Cancer Institute-supported clinical study to evaluate the ability of the company's ProUroScan imaging system to visualize and document abnormalities in the prostate detected or monitored by the digital rectal exam. The results of the clinical study will be submitted to the U.S. Food and Drug Administration (FDA) in support of a 510(k) application in the near future after third party validation of the data. In an earlier clinical study conducted by Artann Laboratories and Dr. Robert Weiss at the Robert Wood Johnson Medical Center, and published in the peer-reviewed journal Urology, 168 patients were assessed using the ProUroScan system to demonstrate the technology's ability to provide an objective and reproducible image or map of the prostate. In an ensuing meeting with the FDA, a modified clinical study was discussed for imaging at least 40 patients using an enhanced version of the ProUroScan imaging system. This study, which closed on September 25 with support from Artann Laboratories, ultimately included 57 patients recruited at the University of Minnesota Veterans Affairs Medical Center in Minneapolis; the Robert Wood Johnson Medical School Division of Urology in New Brunswick, N.J.; AccuMed Research Associates in Garden City, N.Y; Urological Associates of Lancaster in Lancaster, Pa.; and the Mayo Clinic in Rochester, Minn. Source: PRNewswire 10/8/09

Head-to-Head Crossover Study Evaluates Two Non-Calcium Phosphate Binders

Shire plc in October announced the publication in Clinical Nephrology of findings from a head-to-head clinical study comparing the efficacy of two non-calcium based phosphate binders, Fosrenol® (lanthanum carbonate) and sevelamer hydrochloride (Genzyme's Renagel®) in chronic kidney disease (CKD) patients on haemodialysis. In this 12-week crossover study, patients (n=182) were randomized to receive either Fosrenol or sevelamer for four weeks, and then switched to the alternative phosphate binder for the same period. Product doses were predefined to allow a direct efficacy comparison. Doses were based on those used in previous clinical trials and established clinical practice. The study's primary endpoint, change in serum phosphorus from baseline to end of treatment, was evaluated using several statistical analyses. In the completer population (n=119), Fosrenol reduced serum phosphorus by 1.8 mg/dL, compared to 1.3 mg/dL for sevelamer, a statistically significant difference. A statistically significant difference was also observed between the treatments at week 1. Study investigators concluded that the statistically larger reduction within the completer group suggested that Fosrenol may offer greater serum phosphorus reduction in CKD patients on haemodialysis. Source: PRNewswire 10/7/10

Pilot Clinical Study Considers Elderberry Extract for Flu-Like Symptoms

The ability of a proprietary elderberry extract to significantly reduce flu-like symptoms has been demonstrated in a double-blind, placebo-controlled study undertaken on behalf of HerbalScience Group LLC. The pilot, randomized clinical trial was conducted by Dr. Fan-kun Kong, assisted by medical personnel at Shanghai Construction Technical College, China. The study took place during the spring 2009 flu season and involved 64 patients ranging in age from 16 to 60 years. At the time of enrollment in the study, each of the patients had had three or more flu-like symptoms (fever, headache, muscle aches, coughing, nasal mucus discharge, and nasal congestion) for less than 24 hours. Patients were randomized into two groups and for two days were given four doses daily of the proprietary elderberry extract developed by HerbalScience or a placebo. Patients were asked to self-assess their symptoms at specific intervals over the two days. "By 48 hours, nine patients (28 percent) in the group receiving the elderberry extract were symptom-free, 19 patients (60 percent) showed relief from some symptoms and had only one or two mild symptoms, while the remaining four showed symptom improvement but to a lesser degree," said Kong. "By contrast, complete recovery was not achieved by a single patient in the placebo group, and only 16 percent showed improvement in one or two symptoms. For most in the placebo group, symptoms remained the same or even worsened over the 48-hour period." An article by Kong detailing the clinical study has been published in the peer-reviewed scientific journal Online Journal of Pharmacology and PharmacoKinetics. Source: PRNewswire 10/6/09

Preliminary Phase II Results Announced for Gaucher Disease Treatment

Amicus Therapeutics in October announced preliminary results from its randomized, open-label Phase II study to assess the safety, tolerability, and preliminary efficacy of its investigational drug, Plicera™ (afegostat tartrate), in treatment-naive adult patients with Type 1 Gaucher disease. Two dose regimens of Plicera (225 mg three days on/four days off and seven days on/seven days off) were studied during this six-month trial. While all patients enrolled experienced an increase in the level of the target enzyme (GCase) as measured in white blood cells, clinically meaningful improvements in key measures of disease were observed in just one of the 18 patients who completed the study. The preliminary results suggest that treatment with Plicera was generally well tolerated, with no serious adverse events reported. One subject discontinued treatment because of an adverse event (conjunctivitis-related symptoms). Once the data are final, the company plans to further analyze and evaluate the results in collaboration with its partner, Shire Human Genetic Therapies, Inc., and, based on this work, will determine the appropriate next steps for the Plicera program. However, based on these preliminary results, the company does not expect to advance Plicera into Phase III development at this time. Source: PRNewswire 10/2/09

Liver Stabilization Trial Initiated

Vital Therapies, Inc. announced in early October that the first subject has been enrolled in a pivotal trial of its Extracorporeal Liver Assist Device (ELAD) human cell-based liver assist system at California Pacific Medical Center (CPMC) in San Francisco. Todd Frederick, MD, director of Liver Support Services, is the principal investigator for the trial at CPMC. It is anticipated that up to 20 leading academic liver centers in the United States and Europe will take part in the SILVER (Stabilization In LiVER disease) study. The SILVER protocol allows for enrollment of patients with chronic liver disease who have recently suffered an acute event leading to moderate to severe liver failure. The SILVER trial is focusing on stabilization of liver disease so patients can either recover with their own liver intact or live long enough for a liver transplant. More than 120 patients have so far been treated with ELAD in six clinical trials in the United States, United Kingdom, and China. An application for approval to market ELAD in China was filed in September 2007 after a pivotal clinical trial in China. During ELAD therapy, the patient's plasma flows inside hollow fiber cartridges containing cells that process toxins and synthesize proteins and metabolites that are key products of normal human liver function. Source: PRNewswire 10/1/09

First Human Trial Launched for Embryo Culture System for In Vitro Fertilization

Incept BioSystems, Inc. announced in late September that it has initiated the first U.S. human clinical trial of its proprietary SMART Embryo Culture System. The microscale SMART technology platform is designed to improve the in vitro manipulation, performance, and viability of embryos for the treatment of patients undergoing in vitro fertilization (IVF). The study will assess the SMART system's capacity to safely enhance morphological embryo development and survival rates at day three of development, in comparison to the existing practice of growing embryos in a conventional culture dish. The prospective, multicenter, randomized performance study, which will take place at three investigational sites, is expected to enroll approximately 400 to 600 embryos from up to 40 couples who have been diagnosed with infertility and are planning to undergo IVF and embryo transfer. Unlike the current IVF practice of culturing embryos in a static environment (i.e., a microdrop in a culture dish), Incept's microfluidic system provides a continuous, refreshable culture microenvironment while using industry-standard IVF culture medium. It is believed that this dynamic environment may provide a beneficial physical stimulus to the embryos in addition to replenishing the embryos with fresh medium while removing metabolized waste products. Source: PRNewswire 9/30/09

Phase I Study Will Focus on Drug for Pompe Disease

Amicus Therapeutics in September announced it plans to initiate a Phase I study of AT2220 (1-deoxynojirimycin HCl), its investigational drug in development for the treatment of Pompe disease. The primary objective of this study is to evaluate the pharmacokinetics of AT2220 in muscle tissue in healthy adult subjects. The U.S. Food and Drug Administration (FDA) has agreed to Amicus' proposal for the study and subsequently converted the clinical hold of AT2220 to a partial hold to allow the conduct of this study. In June 2008, the company announced the commencement of a Phase II clinical trial of AT2220 in adults with Pompe disease based on data from both preclinical and Phase I studies. In February 2009, the company announced it had suspended enrollment after two patients enrolled in the trial experienced serious adverse events that were probably related to treatment with AT2220. The AT2220 Investigational New Drug application was subsequently placed on clinical hold by the FDA. The company has completed a thorough evaluation of all data from these two subjects and has completed additional preclinical studies of AT2220. Based on these data, the company proposed the planned Phase I study to FDA in order to further evaluate the pharmacokinetics of AT2220 in muscle, the key target tissue in Pompe disease. The open-label, single-dose study will commence in the fourth quarter of this year. The company expects data from this trial to be available in the first quarter of 2010. Source: PRNewswire 9/30/09

Head-to-Head Study Compares Insulin Treatments

Sanofi-aventis in September announced results of a head-to-head study providing further evidence on the efficacy of once-daily, 24-hour basal insulin Lantus® (insulin glargine [rDNA] injection) compared to twice-daily insulin detemir. The study was presented during the 45th Annual Meeting of the European Association for the Study of Diabetes in Vienna. In the randomized, noninferiority, controlled clinical trial of 964 patients, patients taking Lantus required an average daily dose of 43.5 units to achieve the primary endpoint of HbA1c below 7 percent without symptomatic hypoglycaemia compared to patients on insulin detemir, who received 76.5 units--an increase of 76 percent. Despite lower doses of insulin in the glargine group, Lantus once-daily and insulin detemir twice-daily resulted in similar improvements in glycemic control (HbA1c) and a similar risk of hypoglycaemia (primary endpoint: 27.5 percent versus 25.6 percent). Patients in the Lantus arm of the study also achieved significantly lower fasting blood glucose (-63.1 mg/dL Lantus versus -57.7 mg/dL). Lantus is indicated for once-daily subcutaneous administration in the treatment of adult patients with Type 2 diabetes mellitus who require basal (long-acting) insulin for the control of hyperglycaemia and for adult and paediatric patients (6 years and older) with Type 1 diabetes mellitus. Source: PRNewswire 9/30/09

Phase I Study Considers Drug's Potential Against Advanced Solid Tumors

Onyx Pharmaceuticals, Inc. in September announced that it has begun enrolling patients in a Phase I study of ONX 0801, a novel alpha-folate receptor-mediated thymidylate synthase inhibitor, as a potential treatment for advanced solid tumors. This open-label, dose-finding study will evaluate the safety and pharmacokinetics of ONX 0801 in patients with advanced solid tumors. The open-label, dose-finding study is evaluating the safety and pharmacokinetics of ONX 0801 in approximately 60 cancer patients with advanced solid tumors. Cohorts of three to six patients will receive ONX 0801 at escalating doses until a maximum tolerated dose is determined. Each patient will receive a three-hour intravenous infusion of ONX 0801 weekly of repeated 21-day treatment cycles. In preclinical studies, ONX 0801 targeted malignant cells that overexpress the alpha-folate receptor, which is located on the cell's surface and is overexpressed in a number of tumor types with significant unmet needs, including ovarian cancer, lung cancer, breast cancer, and colorectal cancer. ONX 0801 was discovered at the Institute for Cancer Research in the United Kingdom and is licensed to Onyx by BTG International. Source: PRNewswire 9/28/09

Gout Treatment Enters Phase II

BioCryst Pharmaceuticals, Inc. announced in September that it is initiating a Phase II study of BCX4208 for the treatment of gout. The primary objective is to determine the effect of different doses of orally administered BCX4208 on serum uric acid levels in patients with gout. The trial is expected to enroll up to 120 subjects in a randomized, double-blind, placebo-controlled format. The study's primary endpoint is the change in uric acid in the blood compared to baseline measurement prior to treatment. In a previous study of BCX4208 in patients with psoriasis, patients were administered daily doses up to 120 mg for six weeks. Results showed that BCX4208 was safe and well tolerated up to the maximum dose studied, and produced a statistically significant reduction in uric acid concentration in patients. BCX4208 is a next-generation purine nucleoside phosphorylase inhibitor with the potential for once-a day dosing suitable for chronic administration. A recent study has shown that BCX4208 may have utility in inflammatory diseases dependent on T-cells, B-cells, or uric acid. Source: PRNewswire 9/28/09

Company Completes Enrollment of First Mid-Stage GERD Trial

Addex Pharmaceuticals in September announced the completion of enrollment in its Phase IIb trial of ADX10059 as a monotherapy in patients with gastroesophageal reflux disease (GERD), the cause of heartburn and other symptoms. ADX10059 is a first-in-class reflux inhibitor that works by reducing activation of the metabotropic glutamate receptor 5 through negative allosteric modulation. This approach may lead to a new class of drugs that addresses the causes of GERD rather than just the symptoms. Study ADX10059-204 is a double-blind, placebo-controlled, multicenter European trial in 90 GERD patients known to respond well to PPIs. There is a two-week baseline symptom evaluation period followed by two weeks of administration of ADX10059 120 mg twice daily. ADX10059 is used as a monotherapy, so patients in the study do not use PPIs or other acid suppressant therapy during the baseline and study treatment periods. The coprimary endpoints are patient reported symptom control compared to baseline and the effects of ADX10059 on lower esophageal sphincter (LES) function. Objective measures of the effects of ADX10059 on LES function and acid reflux events will be made in a subset of patients using esophageal manometry and pH impedance monitoring. Data are expected to be communicated in late 2009. ADX10059 also is in Phase IIb trials to treat GERD patients who are partial responders to Proton Pump Inhibitors (PPIs) and, separately, as a migraine prophylaxis in patients with frequent migraines. Source: Marketwire 9/28/09

Drug Improves Time Before Breast Cancer Worsens

One of the first of a series of trials to investigate the use of sorafenib--a targeted anticancer drug--for the treatment of advanced breast cancer has found that if it is combined with the chemotherapy drug, capecitabine, it makes a significant difference to the time women live without their disease worsening. Principal investigator of the study, Professor José Baselga, told Europe's largest cancer congress, ECCO 15 – ESMO 34, in Berlin on September 23, "This is the first large, randomized study that demonstrates significant clinical activity of sorafenib in breast cancer when given in combination with chemotherapy. Our results showed that patients who received sorafenib plus capecitabine had a 74 percent improvement in the time they lived without their disease worsening compared to those who received the chemotherapy alone. This is a very positive study and the magnitude of the benefit is such that it suggests that this agent will be an important addition to our therapeutic armory in breast cancer." Sorafenib (Nexavar®) is a potent multikinase inhibitor, which works by interfering with the growth of cancer cells and slowing the growth of new blood vessels within the tumor. Until now, it has only been used in the treatment of kidney and liver cancer. Baselga, who is head of the oncology department at Vall d'Hebron University Hospital (Barcelona, Spain), president of ESMO (European Society for Medical Oncology), and a member of the ECCO (European CanCer Organization) executive committee, and his colleagues in Spain, France, and Brazil enrolled 229 patients with locally advanced or metastatic breast cancer in the double-blind, randomized Phase II clinical trial between June 2007 and December 2008. They randomized the patients to receive capecitabine 1,000 mg/m2 pill taken twice daily for 14 of every 21 days and a placebo (114 women), or capecitabine and sorafenib 400 mg pill taken twice daily continuously (115 women). The first results from the trial only became available in time for the ECCO 15 – ESMO 34 congress, and they show that the average progression free survival (the time that elapses without the cancer getting worse) was 6.4 months for women on capecitabine and sorafenib compared to 4.1 months for women taking the placebo. It is too early for data on overall survival to be available. Source: EurekAlert! 9/23/09

Treatment Could be New Hope for Adrenal Cancer Patients

TGen Clinical Research Services (TCRS) at Scottsdale Healthcare in September announced the start of a clinical trial for a drug designed to combat adrenocortical carcinoma (ACC), a rare but deadly cancer that attacks the adrenal glands. Other than surgery, the only treatment for ACC is the exacting use of a compound called mitotane, a chemical relative of DDT, which the U.S. banned as an insecticide in 1972. TCRS clinicians hope the new compound, OSI-906, developed by OSI Pharmaceuticals Inc. of Melville, N.Y., will stop ACC tumor growth, and perhaps even promote tumor shrinkage, without the toxic side effects of current chemotherapies. The trial will focus on patients with inoperable tumors who have relapsed or failed to respond to conventional therapies. This clinical trial of OSI-906 is expected to last several years and include 135 patients, with 30-40 enrolled at TCRS. As there is no standard therapy available, two-thirds of the patients will receive the drug OSI-906 and the rest a placebo. Sites elsewhere in the U.S., as well as in Europe and Australia, are expected to enroll patients over the coming months. ACC patients often face radical surgery as part of their treatment, because the tumors can be the size of a football. OSI-906 is an orally available small molecule IGF-1R inhibitor that blocks the chemical pathway that otherwise allows the ACC tumors to grow out of control. OSI-906 is expected to have minimal impact on the healthy tissue of the adrenal glands or their normal function. Although ACC is very rare, affecting only one or two people per million, TGen has devoted more than three years of work to developing a new drug against this orphan indication with funding from a patient advocate and ACC survivor who wished to combat what little research he saw being done on the disease. Source: EurekAlert! 9/22/09

New Type of Sirolimus-Eluting Stent Demonstrates Superior Results

A new type of sirolimus-eluting stent (SES) successfully showed significantly greater neointimal suppression than a paclitaxel-eluting stent (PES), with greater vessel wall integrity surrounding the stent, confirming the finding of superiority of the SES over the PES stent for the trial's primary endpoint of in-stent late loss. Results from the RES-ELUTION I Trial on the safety and effectiveness of a new SES in the treatment of coronary artery disease (a single atherosclerotic lesion) in native coronary arteries were presented at the 21st annual Transcatheter Cardiovascular Therapeutics scientific symposium, sponsored by the Cardiovascular Research Foundation. RES-ELUTION I, which began in March 2008, is a multicenter, randomized, single-blind, controlled trial comparing the SES system to the PES system in de novo native coronary artery lesions. A total of 394 subjects were randomized to treatment with either the SES or PES. The new SES utilizes a reservoir technology that incorporates a number of small wells, each acting as a depot into which drug-polymer compositions are loaded. The stent's design achieves both a significant reduction in total polymer load, as well as a reduction in tissue-polymer contact by more than 75 percent compared to conventional drug-eluting stents, in which the entire stent surface is coated with polymer. Its use of a bioresorbable polymer is another theoretical advantage from the safety perspective, allowing the drug-eluting stent to become simple bare metal within the vessel wall approximately three months after deployment. In this clinical trial, detailed arterial responses to the new stent technology were also investigated in vivo using intravascular ultrasound (IVUS). Serial IVUS (immediately poststenting and six-month follow-up) was performed in a predefined IVUS subset of 100 patients (52 SES in 50 patients; 52 PES in 50 patients). Volumetric IVUS analysis demonstrated significantly less neointimal proliferation in the sirolimus-eluting stent, resulting in less late lumen area loss and smaller maximum cross-sectional narrowing (neointimal area/stent area) than PES. Source: EurekAlert! 9/21/09

Company Receives FDA Approval to Commence First ALS Stem Cell Trial

Neuralstem, Inc. in September announced that the U.S. Food and Drug Administration (FDA) has approved its Investigational New Drug application to commence a Phase I trial to treat Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's disease) with its spinal cord stem cells. Neuralstem is the first company to commence a stem cell trial to treat ALS. The trial will study the safety of Neuralstem's cells and the surgical procedures and devices required for multiple injections of Neuralstem's cells directly into the grey matter of the spinal cord. While the trial aims to primarily establish safety and feasibility data in treating ALS patients, the company hopes to be able to measure a slowing down of the ALS degenerative process. Ultimately, 18 ALS patients with varying degrees of the disease will be treated through spinal injections of the company's patented human neural stem cells. The FDA has approved the first stage of the trial, which consists of 12 patients who will receive five to 10 stem cell injections in the lumbar area of the spinal cord. The patients will be examined at regular intervals postsurgery, with final review of the data to come about 24 months later. Neuralstem expects to conduct the trial at Emory University. Source: PRNewswire 9/21/09

Trial Yields Big Results for Weight Management

Arena Pharmaceuticals, Inc. in September reported positive, highly significant top-line results from the BLOSSOM (Behavioral modification and LOrcaserin Second Study for Obesity Management) trial. BLOSSOM confirms the results previously reported for the BLOOM (Behavioral modification and Lorcaserin for Overweight and Obesity Management) trial and completes the lorcaserin Phase III pivotal registration program of 7,190 patients evaluated for up to two years. Arena plans to submit a New Drug Application for lorcaserin to the U.S. Food and Drug Administration (FDA) in December. In the one-year BLOSSOM trial, lorcaserin met all primary efficacy and safety endpoints. Patients achieved highly significant categorical and absolute weight loss. Lorcaserin was very well tolerated and was not associated with depression or suicidal ideation. The integrated echocardiographic data set from BLOSSOM and BLOOM rules out a risk of valvulopathy in lorcaserin patients according to criteria requested by the FDA. Treatment with lorcaserin also resulted in significant improvements as compared to placebo in multiple secondary endpoints associated with cardiovascular risk. Arena plans to present detailed data from both the BLOOM and BLOSSOM trials at the 27th Annual Scientific Meeting of the Obesity Society, scheduled for October 24-28 in Washington, D.C. BLOSSOM was a double-blind, randomized, placebo-controlled trial that enrolled 4,008 patients in approximately 100 sites in the U.S. Source: PRNewswire 9/18/09

Company Receives SFDA Approval for Clinical Trial of Abuse-Resistant Opioid Drug

China Aoxing Pharmaceutical Co., Inc. in September announced that its Clinical Trial Application for Tilidine/Naloxone Capsules, an opioid drug with abuse-resistant property, was officially approved by the China State Food and Drug Administration (SFDA). The company hopes to begin the clinical trial by the end of this year, and estimates that receipt of a market license could occur in 2011. The drug is designated as a Class III New Medicine with approximately at least three-year market exclusivity protection upon marketing clearance by the China SFDA. Tilidine/Naloxone Capsules were developed with China Aoxing's proprietary technology, which combines Tilidine, an effective opioid agonist, with Naloxone, an opioid antagonist, to address moderate to severe pain, such as cancer pain and postoperative pains. Based on clinical trials in Europe, when Tilidine/Naloxone Capsules were taken as directed, pain relief was provided and Naloxone passed through the body without observed clinical effect. If the capsules are crushed or dissolved in alcohol, which are common approaches abusers use to tamper with an opioid product in order to gain euphoria, both Tilidine and the Naloxone are released, and the euphoric effect of Tilidine is significantly reduced. Source: Marketwire 9/17/09

First Clinical Study with Hospitalized H1N1 Infected Patients to Commence

CEL-SCI Corp. announced in September that the U.S. Food and Drug Administration has indicated that the company can proceed with its first clinical trial to evaluate the effect of its investigational LEAPS-H1N1 treatment on the white blood cells of hospitalized H1N1 patients. The initiation of CEL-SCI's rapidly accelerated LEAPS-H1N1 clinical development program builds on CEL-SCI's work with its Ligand Epitope Antigen Presentation System (L.E.A.P.S.™) technology in the context of H1N1. The technology is a novel T-cell modulation platform technology that allows the company to direct an immune response against specific disease epitopes. In the case of CEL-SCI's investigational LEAPS-H1N1 treatment, this involves nonchanging regions of H1N1 pandemic flu, avian flu (H5N1), and the Spanish flu. This is intended to enable stimulation of the specifically needed immune responses, while avoiding the administration of regions of H1N1 and other viruses that may exacerbate the problem of cytokine storm, which CEL-SCI scientists believe may be involved in the death of some H1N1 patients. The L.E.A.P.S. technology combines a small peptide that activates the immune system with a small peptide from a disease-related protein, such as the H1N1 hemagglutinin molecule, to make an investigational product that induces defined immune responses. Source: PRNewswire 9/16/09

Phase I Study Initiated for Compound to Boost Erythropoietin Production

Akebia Therapeutics, Inc. announced in September that it has initiated dosing of healthy volunteers in the first-in-human Phase I study for AKB-6548, an orally bioavailable hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor in development for anemia. AKB-6548 has been designed to increase the natural production of erythropoietin, a glycoprotein hormone that controls red blood cell production, in anemic patients. The study is designed to evaluate the safety, tolerability, and pharmacokinetics of single ascending doses of AKB-6548 in healthy volunteers. In addition, the efficacy of AKB-6548 will be ascertained by measuring erythropoietin and other biomarker responses. The trial will involve up to 48 healthy volunteers and will be conducted at Medpace, Inc. in Cincinnati, Ohio. The study is expected to be completed this year. Akebia will initially target patients with chronic renal disease and predialysis patients, two patient populations that are currently undertreated for anemia. Source: Marketwire 9/15/09

Positive Results Seen in Phase I Multiple Sclerosis Trial

Artielle ImmunoTherapeutics announced in September that results from a Phase I safety study of RTL1000, a recombinant T-Cell receptor ligand specific for an immunodominant MOG peptide, in multiple sclerosis (MS), were presented at the Congress of the European Federation of Neurological Societies in Florence, Italy. The presentation showed that the study met its primary objective, which was to evaluate the safety profile and determine the maximum tolerated dose of a single IV dose of RTL1000. Secondary objectives of the study were also met; these were to determine the pharmacokinetic profile of RTL1000 and assess immunologic parameters in a subset of MS patients. This was a first-in-human, double-blind, placebo-controlled trial that enrolled 34 subjects with relapsing remitting and secondary progressive MS at six centers in the United States. All subjects were followed for clinical and MRI changes, pharmacokinetics, and cytokine levels in plasma and blood mononuclear cells. The trial demonstrated that RTL1000 was safe and did not exacerbate MS disease activity at any of the tested doses. Although not designed to assess efficacy, the study's immunological data from a subgroup of patients indicated RTL1000 was biologically active. Source: PRNewswire 9/14/09

Phase III Trial in Metastatic Pancreatic Cancer Discontinued

Sanofi-aventis and Regeneron Pharmaceuticals, Inc. in September announced the discontinuation of a Phase III trial that was evaluating aflibercept (VEGF Trap) plus gemcitabine versus placebo plus gemcitabine for the first-line treatment of metastatic pancreatic cancer (VANILLA), based on the recommendations by an independent data monitoring committee. As part of a planned interim efficacy analysis, the committee determined that the addition of aflibercept to gemcitabine would be unable to demonstrate a statistically significant improvement in the primary endpoint of overall survival compared to placebo plus gemcitabine in this study. The types and frequencies of adverse events reported on the combination arm with aflibercept were generally as anticipated. With the closure of the study, a detailed analysis of the efficacy and safety results will be conducted by the companies and results will be presented at a future medical meeting. Sanofi-aventis and Regeneron have notified the study investigators and appropriate regulatory authorities of the decision to discontinue the study. Patients in the study will continue to be provided access to aflibercept at the determination of the study investigators in consultation with the patients. Metastatic pancreatic cancer is among the most intractable cancers. Clinical development of new therapies, including anti-VEGF agents, has been generally characterized by a failure to achieve significant incremental clinical benefit over existing treatments. Sanofi-aventis indicated that it remains committed to ongoing Phase III trials of aflibercept in colorectal cancer, non-small cell lung cancer, and hormone-refractory metastatic prostate cancer, each of which is currently more than 70 percent enrolled. Source: PRNewswire 9/11/09

Company Receives Clearance to Initiate Trials for Multi-IAP Antagonist

Ascenta Therapeutics announced in September that, following the approval by the U.S. Food and Drug Administration of its Investigational New Drug application for AT-406, an orally active, small molecule, multi-IAP antagonist, the company will initiate a Phase I clinical trial in patients with advanced cancer during the fourth quarter of 2009. The multicenter, single-agent, open-label, accelerated dose-escalation study will evaluate safety and determine the maximum tolerated dose and optimal dosing schedule of AT-406 in patients with advanced lymphomas and solid tumors. Secondary endpoints will include pharmacodynamic and pharmacokinetic parameters and evidence of antitumor activity. AT-406 is designed to promote programmed cell death (apoptosis) in tumor cells by blocking the activity of at least three "inhibitors of apoptosis proteins," or IAPs, (including XIAP, c-IAP1, and c-IAP2) to create conditions in which apoptosis can proceed. IAPs are key components of the complex cascade of protein signaling that activates enzymes called caspases to initiate breakdown of the cancer cell. AT-406 is thought to mimic the activity of Smac (second mitochondria-derived activator of caspases) by binding to XIAP and preventing it from inhibiting caspase activation. Upon binding, AT-406 induces rapid degradation of cIAP-1/2 proteins and promotes apoptosis through activation of caspase-8 and the death-receptor complex. AT-406 has demonstrated strong single-agent antitumor activity in multiple preclinical xenograft models of human cancer, including breast cancer, pancreatic cancer, prostate cancer, and lung cancer. AT-406 has also been shown to work synergistically with conventional chemotherapeutic and targeted agents (such as tyrosine kinase inhibitors) in preclinical tumor models. Source: PRNewswire 9/10/09

Early Results Announced for 2009 H1N1 Influenza Vaccines

According to a recent announcement from the National Institutes of Health (NIH), "We are encouraged by reports that are now emerging from various clinical trials of 2009 H1N1 influenza vaccines, conducted by various vaccine manufacturers. We expect additional companies to announce their preliminary trial results shortly. The early data from these trials indicate that 2009 H1N1 influenza vaccines are well tolerated and induce a strong immune response in most healthy adults when administered in a single unadjuvanted 15-microgram dose. We congratulate the companies on these trials, which are an important part of the ongoing worldwide effort to develop vaccines to protect the public from 2009 H1N1 influenza." The National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, also is conducting clinical trials of 2009 H1N1 influenza vaccines, produced by Sanofi Pasteur and CSL Limited. The NIAID trials are testing two different dosages (15 micrograms versus 30 micrograms) and evaluating the immune response to one and two doses of these vaccines. More than 2,800 people are participating in ongoing NIAID trials of these vaccines. "We are pleased to note that preliminary analyses of early data from the NIAID trials align with the recently announced findings and those to be announced imminently by other companies in that both vaccines studied induced what is likely to be a protective immune response in most adults following a single dose in the same amount (15 micrograms) used in seasonal flu vaccines," the NIH said. Source: EurekAlert! 9/11/09

Drug for Preventing Protracted Labor Successful in Phase II

Karolinska Development in September announced that one of its portfolio companies, Dilafor AB, has concluded an extensive clinical study of its candidate drug, tafoxiparin, a new drug substance for the prevention of protracted labor during childbirth. The promising results of the Phase II trial bring the project closer to exit in line with Karolinska Development's business strategy. The tafoxiparin trial was designed to measure the effect on labor time after preventive treatment using the candidate drug. A total of 263 women at 18 clinics in Sweden were included in the randomized, double-blind, placebo-controlled study, conducted over a two-year period. The treatment, which was administered during the last phase of pregnancy, was shown to be safe and well tolerated. Although labor time was shorter in the treated group, the effect did not reach statistical significance. However, further analyses of results suggest that treatment with tafoxiparin provides beneficial effects, including a statistically significant reduction in the number of women with labor times in excess of 12 hours; fewer complications as a cause of protracted labor; and fewer caesarean sections as a result of protracted labor. The company will now start actively seeking a collaboration partner with whom it can carry out a Phase III program. Source: PRNewswire 9/4/09

Australian Company Receives Clearance to Start U.S. Haematological Disorders Trials

Cytopia Limited's Investigational New Drug (IND) application for CYT387 has passed U.S. Food and Drug Administration (FDA) review. CYT387 is a small-molecule oral JAK1/JAK2 kinase inhibitor designed to treat various haematological disorders. The company's IND application is now active and Cytopia is able to proceed with clinical trials for CYT387 in the United States. CYT387 will be the second of Cytopia's compounds to enter clinical trials. The company's anticancer vascular-disrupting agent CYT997 is already in Phase II studies in Australia. Hyperactivity of the JAK2 enzyme is known to cause a number of haematological conditions known as myeloproliferative disorders (MPDs). This group of diseases includes myelofibrosis, polycythemia vera, and essential thrombocythemia. In addition, Cytopia has identified potential activity of CYT387 in a range of cancers, which may substantially enlarge the value of this compound. Dual JAK1/JAK2 inhibition is likely to increase the clinical benefit in these disease indications and broaden the therapeutic opportunities for CYT387. Preparations for the company's initial Phase I/II trial of CYT387 in patients with myelofibrosis are currently being finalized. Myelofibrosis is a life-threatening scarring of the bone marrow. This study will be undertaken at the Mayo Clinic in Rochester, Minn. The company anticipates opening the study to enrollment in the fourth quarter of 2009. Further details of the study will be disclosed following site ethics committee approval. Source: PRNewswire 9/3/09

Positive Phase III Results Seen for Rheumatoid Arthritis Treatment

Nitec Pharma AG in September announced positive results from the second pivotal Phase III trial for its lead product, Lodotra™. The CAPRA-2 study (Circadian Administration of Prednisone in Rheumatoid Arthritis-2) was a 12-week, multicenter, double-blind trial evaluating the safety and efficacy of Lodotra for the treatment of rheumatoid arthritis (RA). In total, 350 patients, all inadequate responders to DMARD therapy, were randomized in one of two arms to receive either Lodotra (5 mg once daily) or placebo in addition to their existing therapy. The primary efficacy endpoint was the ACR-20 response rate, which is defined as at least a 20 percent improvement in a number of disease-specific criteria. The key secondary endpoint was the change in the duration of morning stiffness of the joints. CAPRA-2-data will be used to file for U.S. marketing approval with the Food and Drug Administration together with the data already available from the CAPRA-1 pivotal Phase III trial, which has shown the superiority of Lodotra over standard prednisone treatment. Lodotra-treated patients showed an ACR-20 response of 49 percent compared to 29 percent in the placebo group. The reduction of morning stiffness was 44 percent in the Lodotra group (21 percent in the placebo group). Source: PRNewswire 9/2/09

Trial Results Signal Advances Against Skin Cancer

Analyses of clinical trial results published recently in the New England Journal of Medicine show a potential new investigational therapy for advanced and metastatic basal cell skin cancer. The study, conducted at Translational Genomics Research Institute (TGen) Clinical Research Service (TCRS) at Scottsdale Healthcare and two other sites, appears to demonstrate tumor shrinkage and limited side effects. TCRS is a strategic alliance between TGen and Scottsdale Healthcare. These findings are significant because no proven therapy exists for advanced basal cell carcinoma (BCC). The trial, sponsored by Genentech, included clinicians at TCRS, the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, and Karmanos Cancer Institute in Detroit. The results demonstrated that GDC-0449, a Hedgehog Pathway Inhibitor, appears to shrink tumors in locally advanced and metastatic BCC. Known as the "Hedgehog" trial, the clinicians observed a durable clinical benefit--defined as tumor shrinkage visible on x-ray or other physical exam or improvement in symptoms without tumor growth--in 18 of 33 patients evaluated. Others had stable disease for prolonged periods of time. Only 4 patients had progression of disease. Source: EurekAlert! 9/2/09

Interim Phase II Data Presented on Brain Cancer Treatment

Peregrine Pharmaceuticals, Inc. in September reported that clinical investigators presented interim Phase II data showing that its brain cancer agent Cotara® appeared well tolerated and demonstrated encouraging signs of efficacy in patients with glioblastoma multiforme (GBM), the deadliest form of brain cancer. The data, presented at the XIV World Congress of Neurological Surgery Annual Meeting, covered 10 recurrent GBM patients at first relapse treated at All India Institute of Medical Sciences as part of an ongoing 40-patient trial. Eight males and two females with a mean age of 51 years received a single intratumoral infusion of Cotara. Currently, follow-up duration ranges from between seven to more than 73 weeks, with an interim median recurrence-free survival of 33 weeks and an interim median overall survival of 41 weeks. Expected survival for patients with GBM is approximately 24 weeks from time of disease recurrence. Based on this interim data, the study authors conclude that Cotara appears to be feasible and tolerable, and that it has encouraging signs of efficacy in recurrent GBM patients. The open-label study is designed to enroll up to 40 patients who have experienced a first relapse. The primary objective of the trial is to confirm the maximum tolerated dose of Cotara in GBM patients at first relapse. Secondary objectives include estimates of overall patient survival, progression-free survival, and the proportion of patients alive at six months. In addition to the Phase II trial now under way in India, a dosimetry and dose confirmation trial in GBM patients at leading U.S. academic brain cancer centers is nearing completion. Cotara has been granted orphan drug status and fast track designation for the treatment of GBM and anaplastic astrocytoma by the U.S. Food and Drug Administration. Source: PRNewswire 9/2/09

Cholesterol Treatment Demonstrates Long-Term Efficacy and Tolerability

New data presented in early September showed that in patients treated with Livalo (pitavastatin), high-density lipoprotein cholesterol (HDL-C) concentrations increased, and nearly three-fourths of patients attained low-density lipoprotein cholesterol (LDL-C) targets, with results sustained over 52 weeks. Additionally, the drug was found to have comparable efficacy to atorvastatin and simvastatin, as measured by reduction in LDL-C from baseline. The Phase III data were presented at the European Society of Cardiology Congress in Barcelona, Spain. The primary objective of the two double-blind, active-controlled studies was to demonstrate noninferiority of Livalo to atorvastatin and simvastatin, as measured by the reduction of LDL-C. Secondary objectives of the study were to assess National Cholesterol Education Program and European Atherosclerosis Society LDL-C target attainment, other lipid and lipoprotein fractions, safety, and tolerability. An open-label extension study was also conducted to assess the long-term safety and tolerability of Livalo 4 mg once daily for up to 52 weeks. In the first study, a total of 830 patients were randomized to one of four treatment groups: Livalo (2 mg or 4 mg) or atorvastatin (10 mg or 20 mg), once daily. Results showed that the drug was comparable to atorvastatin in terms of reduction in LDL-C, and no significant differences emerged in the other endpoints. In the second study, a total of 857 patients were randomized to Livalo (2 mg or 4 mg) or simvastatin (20 mg or 40 mg), once daily. Results showed that Livalo 4 mg and simvastatin 40 mg were comparable in LDL-C reduction, with low-dose Livalo resulting in a greater reduction in LDL-C than simvastatin 20 mg. Additionally, low-dose Livalo showed significantly better decreases in total cholesterol and non-HDL-C than simvastatin 20 mg. Moreover, the percentage of patients who met the LDL-C goal was greater with low-dose Livalo compared to simvastatin 20 mg. The extension study demonstrated a favorable safety and tolerability profile for Livalo 4 mg over the 52-week trial. In addition, a higher proportion of Livalo-treated patients met the defined LDL-C target at the end of the extension study than at the end of the core study. Steady increases in HDL-C were observed throughout the extension period, reaching more than 14 percent. Source: PRNewswire 9/1/09

Company Submits NDA for Type 1 Gaucher Disease Therapy

Shire plc in early September reported that it has completed its submission of a New Drug Application (NDA) for velaglucerase alfa, its enzyme replacement therapy in development for the treatment of Type 1 Gaucher disease, with the U.S. Food and Drug Administration (FDA). The company also announced positive results from the final two Phase III studies of velaglucerase alfa, with both studies reaching all of their primary and secondary endpoints, and that it is on track to submit a European filing for velaglucerase alfa by the end of 2009. Shire's velaglucerase alfa program included the largest and most comprehensive set of Phase III clinical trials conducted to date for Gaucher disease. More than 100 patients at 24 sites in 10 countries around the world have participated in the clinical studies. All three Phase III studies of velaglucerase alfa demonstrated positive results. The product was generally well tolerated in both treatment-naive and previously treated Gaucher patients. One study examined velaglucerase alfa in naive patients, another was a head-to-head comparison of velaglucerase alfa and imiglucerase, and a third was a switch study from imiglucerase to velaglucerase alfa. The specific data from all three trials will be presented at future scientific meetings. Source: PRNewswire 9/1/09

Vaccine Trial Initiated Against Leishmaniasis in Sudan

The Infectious Disease Research Institute (IDRI) announced in August the start of a clinical trial in Sudan to test its leishmaniasis vaccine candidate for the treatment of post kala-azar dermal leishmaniasis (PKDL), a complication of visceral leishmaniasis (VL) that is observed in 50 percent of patients treated for VL in the country, predominantly affecting children. This trial reflects IDRI's commitment to develop innovative, affordable products against all forms of leishmaniasis, one of the most neglected infectious diseases. PKDL is characterized by extensive skin lesions that can require months of additional daily injections of drugs that are either toxic, incompletely effective, or very expensive. Importantly, PKDL patients play a significant role in the transmission of the disease, because the parasite responsible for leishmaniasis is present in large numbers in the skin lesions and can be transmitted to healthy persons through the bites of sandflies. This new Phase I clinical trial is testing the vaccine candidate's safety and ability to induce an immune response against the disease when given in combination with a standard drug treatment. A total of 42 patients diagnosed with persistent PKDL will be recruited in the double-blind study. In addition to the daily drug therapy, 28 patients will be randomly assigned to receive IDRI's vaccine candidate and 14 to receive placebo, both administered as three subcutaneous injections every other week. The total duration of safety follow-up of each patient will be approximately 12 months. IDRI, a Seattle-based not-for-profit, has been working on leishmaniasis for more than 15 years with the support of the National Institutes of Health and the Bill & Melinda Gates Foundation. IDRI's leishmaniasis vaccine candidate has already been evaluated with favorable results in completed clinical trials in healthy adults in the U.S., Colombia, and India, and in adult patients with different forms of leishmaniasis in Peru and Brazil. Source: PRNewswire 8/27/09

Regulatory Approval Allows Start of Human Testing of Avian Flu Vaccine

Medicago Inc. in August announced that it has received clearance from Health Canada to commence a Phase I human clinical trial with its H5N1 avian influenza vaccine. Enrollment of volunteers is now under way. The placebo-controlled, double-blind, dose-escalating study will evaluate safety, tolerability, and immune response of the vaccine candidate in up to 48 healthy volunteers between the ages 18 to 60. Volunteers will receive two doses, injected 21 days apart, of either a placebo or the influenza vaccine at doses of 5, 10, or 20 micrograms. The trial will take place at the Vaccine Evaluation Center of McGill University in Montreal, Canada. Results of this study are expected during the fourth quarter of 2009. The trial will be the first in which a plant-based vaccine will be injected into humans in Canada. Formulated to protect against the Indonesian influenza virus, the vaccine is manufactured in Nicotiana benthamiana, a relative of the tobacco plant, using the company's proprietary technology. Source: PRNewswire 8/25/09

Treatment for Shingles Complication Falls Short in Phase IIa

Valeant Pharmaceuticals International in August announced preliminary results from its Phase IIa proof-of-concept clinical trial of retigabine for the treatment of pain associated with postherpetic neuralgia (PHN), a painful and common complication of shingles. While retigabine was generally well tolerated, the study did not meet its prespecified primary efficacy endpoint. Further detailed analyses are warranted and are ongoing. "As is typical in many proof-of-concept studies, these results are inconclusive at this time with regard to the potential utility of retigabine in PHN patients," stated J. Michael Pearson, chairman and chief executive officer. "The treatment duration was relatively short and with limited statistical powering for the study overall. There are many additional analyses that have yet to be undertaken, and these will be performed over the next several months. Moreover, given that the provisional results from this study will not impact the submission of our New Drug Application for retigabine in epilepsy, we remain focused on the submission as our number one priority." The randomized, double-blind, placebo-controlled study of 187 patients was conducted in approximately 50 trial locations. Study patients were titrated to their individually determined maximum tolerated dose within the range of 300 mg to 900 mg per day. The primary outcome assessment was the comparison of the average pain intensity over the last seven days of maintenance therapy with retigabine versus placebo. The drug, a first-in-class neuronal potassium channel opener, is currently in late-stage development as an adjunctive treatment for patients with partial-onset seizures. In Phase III epilepsy trials, retigabine was shown to be efficacious with a demonstrated reduction in monthly seizure rates. Source: PRNewswire 8/24/09

Company Receives Conditional FDA Approval for Ventricular Assist Device Study

World Heart Corp. announced in August that it has received conditional approval from the Food and Drug Administration (FDA) to begin a bridge-to-transplant study of the Levacor ventricular assist device at 10 U.S. centers. The company is required to provide some additional information to the FDA within 45 days, but the study is permitted to begin upon receipt of clinical center institutional review board approvals. WorldHeart has been working closely with a number of clinicians and clinical sites that are interested in participating in the Levacor Study. Center expansion beyond the initial 10 sites will be based on a supplemental Investigational Device Exemption application and subsequent FDA approval. Study enrollment will involve approximately 200 subjects, with an opportunity to demonstrate statistical significance through a planned interim analysis at approximately 150 subjects. The device is the only bearingless, fully magnetically levitated, implantable centrifugal pump to enter clinical trials. The pump uses magnetic levitation to fully suspend the spinning rotor, its only moving part, inside a compact housing. Source: PRNewswire 8/20/09

IND for Spinal Cord Injury Placed On Hold

Geron Corp. in August announced that its Investigational New Drug (IND) application for GRNOPC1, a cell therapy for neurologically complete, subacute spinal cord injury, has been placed on clinical hold by the Food and Drug Administration (FDA) pending the agency's review of new nonclinical animal study data submitted by the company. A clinical hold is an order that the FDA issues to a sponsor to delay a proposed trial or to suspend an ongoing trial. Since filing the IND, Geron has been undertaking studies to enable dose escalation of its spinal cord injury product, and has been investigating application of the product to other neurodegenerative diseases. The company has also been performing additional product characterization and conducting further animal studies. Data from this work has been submitted to the FDA. Geron will work closely with the FDA to facilitate their review of the new data and to release the clinical hold. No patients have yet been treated in this study. Source: Geron press release 8/18/09

Phase IIb Results Published on Herbal Extract for Rheumatoid Arthritis

Phytomedics Inc. in August announced the publication of results from a six-month, Phase IIb clinical trial with an extract of Tripterygium wilfordii Hook F (TwHF), to be developed as PMI-001, in patients with rheumatoid arthritis, in the August 18 issue of the Annals of Internal Medicine. The TwHF extract, or thundergod vine, was shown to be clinically superior to sulfasalazine (SSZ) using the standard American College of Rheumatology (ACR) criteria with a comparable safety profile. This randomized, double-blind, active-controlled study was conducted at 11 sites in the U.S., under the auspices of the National Institutes of Health's National Institute of Arthritis and Musculoskeletal and Skin Diseases. Patients received the TwHF extract 180 mg/day, divided TID (n=60) or SSZ 2 g once daily (n=61) for 24 weeks. The primary endpoint of the study was a 20 percent improvement in disease activity by ACR criteria (ACR20). At six months 67.6 percent of PMI-001-treated patients versus 36 percent of SSZ-treated patients achieved at least a 20 percent improvement in disease activity. In the TwHF group, ACR 50 and ACR 70 responses were observed in 54.1 percent and 37.8 percent of patients. In the SSZ group, both ACR50 and ACR70 responses were 4 percent. Significant improvement was seen with all endpoints as early as two weeks. Patients receiving TwHF had no progression of mean joint space narrowing and erosion scores. According to the company, potential applications of this botanical drug candidate beyond rheumatoid arthritis include a wide range of autoimmune disorders including lupus, psoriasis, inflammatory bowel disease, and multiple sclerosis. Source: PRNewswire 8/19/09

Radio Frequency Technology Fights Stretch Marks

Pollogen's TriPollar™ technology, a radio frequency treatment for facial and body contouring, has been clinically proven to be effective against stretch marks (striae distensae) in a recent pilot study described in a peer-reviewed paper in the Journal of Dermatological Treatment. In the clinical study, 17 females with stretch marks underwent six weekly treatments with the apollo™ device--Pollogen's latest aesthetic solution based on TriPollar technology. Results showed that at one week after the final (sixth) treatment, 38.2 percent and 11.8 percent of the patients were assessed to have 25-50 percent and 51-75 percent improvement in the appearance of their stretch marks, respectively. The long-term effect of the treatment was confirmed during the six-week follow up, which showed that a higher percentage of the patients were rated to have improvement of their stretch marks, including 26.5 percent and 5.9 percent showing 51-75 percent and >75 percent improvement, respectively. None of the participants were rated as having no improvement in their clinical appearance of stretch marks. Patient satisfaction was also measured, and 65 percent of patients reported that they were very satisfied with the treatment, 23 percent were satisfied, and 12 percent were slightly satisfied. Source: PRNewswire 8/18/09

Firm to Begin Phase II Traumatic Brain Injury Trials in Switzerland

Oxygen Biotherapeutics, Inc. in August announced that the company has received approval to begin a Phase II dose-escalation clinical trial in Switzerland for use of Oxycyte® in traumatic brain injury (TBI). Oxycyte is the company's perfluorocarbon (PFC) therapeutic oxygen carrier. The company has named the 128-patient study Safety and Tolerability of Oxycyte in Patients with Traumatic Brain Injury (STOP TBI). The first patient is expected to be enrolled in September. Since study participants will all be emergency cases, it is not possible to pinpoint a date for the actual first patient. A contract research organization, PFC Pharma Focus AG, will supervise the study. The principal investigator is Dr. Michael Reinert of the Department of Neurosurgery at the University Hospital of Berne. The Insel Hospital in Berne will be the first of the planned seven trial centers in Switzerland and four in Israel to begin enrolling patients. The other trial centers planned for the Swiss study are in Zurich, Aarau, St. Gallen, Basel, Geneva, and Lausanne. The dose-escalation studies will focus on finding the lowest dose of Oxycyte that provides clinical benefit in traumatic brain injury while minimizing adverse effects. Dose levels of Oxycyte would start at 1.0 ml/kg body weight and escalate in steps to 2.0 ml/kg, and 3.0 ml/kg for subsequent patient cohorts. Escalation of dose will only occur after a favorable review of safety data by an independent data safety monitoring board. Source: PRNewswire 8/14/09

Study Shows Orally Inhaled Migraine Therapy Effective

A new study shows an investigational, orally inhaled therapy is effective in treating migraines. The multicenter, randomized, double-blind, placebo-controlled Phase III FREEDOM-301 trial for the therapy, Levadex™, shows study participants had significant relief from symptoms such as pain, nausea, and light and sound sensitivity when compared to placebo treatment. According to trial results, this therapy provided pain relief in 30 minutes and sustained relief for 48 hours after dosing in patients with moderate or severe migraine attacks. Following treatment for a single attack, more than 500 patients opted to continue in an open-label, long-term safety study. The trial, conducted pursuant to a Special Protocol Assessment with the U.S. Food and Drug Administration, is sponsored by MAP Pharmaceuticals, Inc. Patients administer Levadex themselves using the company's proprietary Tempo® inhaler. The drug is a novel formulation of dihydroergotamine, a drug used intravenously in clinical settings for many years to effectively and safely treat migraines. Source: EurekAlert! 8/11/09

Diarrhea Treatment Fails for Metastatic Melanoma Patients

Patients with Stage III or IV melanoma taking ipilimumab and the oral steroid budesonide to reduce side effects did not have less diarrhea, a known side effect of ipilimumab, according to results of a Phase II trial published in Clinical Cancer Research. Researchers gave 10 mg/kg of ipilimumab to 115 patients every three weeks, for four doses. This was combined with daily budesonide for one group and placebo control for another. After four months of treatment, they found that budesonide did not affect the rate of diarrhea--it occurred in 32.7 percent of patients treated with the drug and 35 percent of those who received placebo, according to the study. Median overall survival was 17.7 months among those treated with budesonide compared with 19.3 months among those who received placebo. Additionally, the researchers saw antitumor responses in 10 to 15 percent of patients, without an apparent difference between patients treated with budesonide and those who received placebo. Ipilimumab (also known as MDX-010 or MDX-101) is in a class of drugs called monoclonal antibodies, which stimulate the body's own immune system to fight disease. It is currently in clinical trials for the treatment of melanoma. Budesonide is currently used for the treatment of inflammatory bowel disease, asthma, and noninfectious rhinitis, and for the treatment and prevention of growths in the nasal cavity. Source: EurekAlert! 8/11/09

Drug Increases Bone Density, Cuts Fracture Risk in Prostate Cancer Survivors

Twice-yearly treatment with denosumab, a new targeted therapy to stop bone loss, increased bone density and prevented spinal fractures in men receiving androgen-deprivation therapy for prostate cancer. The report from an international research study, the first to document reduced fracture risk in men receiving the hormone-blocking treatment, appears in the August 20 New England Journal of Medicine. Denosumab--a fully human monoclonal antibody that blocks the action of osteoclasts, the cells that break down bone in the normal process of bone remodeling--is also being investigated to prevent fractures in women with osteoporosis. The current study was a Phase III trial supporting the application for Food and Drug Administration approval filed by Amgen Inc., the primary sponsor of the report. Men undergoing androgen-deprivation therapy for nonmetastatic prostate cancer were enrolled at 156 centers in North America and Europe and randomly assigned to receive injections of either denosumab or a placebo every six months for three years. Participants were also instructed to take daily calcium and vitamin D supplements during the study period. Among the more than 900 participants who completed the study, denosumab significantly increased bone density at all the monitored sites--including the lumbar spine, total hip, and femoral neck--and reduced new vertebral fractures by 62 percent. Bone density at the radius, one of the bones in the forearm, also increased in the treatment group, an improvement not seen with other osteoporosis drugs. Few adverse events were associated with treatment, and there were no reports of osteonecrosis of the jaw, a problem reported in some patients taking bisphosphonates. Along with the Amgen grant, the study received support from the National Institutes of Health and the Prostate Cancer Foundation. Source: EurekAlert! 8/11/09

Pseudobulbar Affect Treatment Hits Endpoint in Phase III Trial

Avanir Pharmaceuticals, Inc. in August announced that the investigational drug Zenvia™ (dextromethorphan/quinidine) met its primary efficacy endpoint in the treatment of pseudobulbar affect (PBA), a condition marked by frequent, unpredictable, and often intense emotional outbursts, in the confirmatory, international, multicenter, randomized, double-blind Phase III STAR trial. The primary efficacy analysis was based on the changes from baseline in crying/laughing episode rates recorded in patient diaries. Both Zenvia 30/10 mg and 20/10 mg provided a statistically significant reduction in episode rates over the course of 12 weeks when compared to placebo. A total of 110, 107, and 109 patients were randomized to the Zenvia 30/10 mg group, the Zenvia 20/10 mg group, and the placebo group, respectively. The proportion of patients reporting at least one serious adverse event was 6.5 percent in the Zenvia 30/10 mg group, 8.8 percent in the Zenvia 20/10 mg group, and 10.4 percent in the placebo group. Overall, there were seven deaths in the study, all in patients with underlying amyotrophic lateral sclerosis. In total, three deaths occurred in the Zenvia 30/10 mg arm, three in the 20/10 mg arm, and one in the placebo arm. Of the seven deaths that were reported, five of the deaths (four in the Zenvia treatments arms and one in the placebo arm) occurred at least five days after study drug had been discontinued. There was one reported death in the Zenvia 20/10 mg group that was considered possibly treatment-related, which occurred five days after study drug had been discontinued. The study involved 52 sites in the U.S. and Latin America; its double-blind phase was followed by a three-month, open-label extension study. Source: EurekAlert! 8/11/09

Success Noted in Phase III Asian Clinical Trials of Flu Treatment

Biota Holdings Limited in August announced successful results from the Asian Phase III clinical trials of CS-8958 (laninamivir), its second generation influenza treatment. Laninamivir is a long-acting neuraminidase inhibitor and is co-owned with Daiichi Sankyo. In the trial in adults, a single inhaled dose of laninamivir was shown to be as effective as oseltamivir (Tamiflu) administered orally twice daily for five days. A parallel Phase II/III trial of CS-8958 in pediatric patients also met the primary and secondary endpoints compared to oseltamivir. The Phase III study was conducted by Daiichi Sankyo in Japan, Taiwan, Hong Kong, and Korea in approximately 1,000 adult patients who had confirmed, naturally acquired influenza A or B. Patients in the trial received either 20 mg or 40 mg of laninamivir as a single inhaled dose or 75 mg of oseltamivir twice daily for five days. Participants in the trial were distributed equally across three treatment groups. The primary endpoint of the trial was time to symptom resolution, while the secondary endpoint was time for body temperature to return to normal. Both doses of laninamivir were as effective as oseltamivir and were well tolerated. The parallel, double-blind pediatric study of laninamivir was conducted in Japan in approximately 180 children aged 9 or younger. A clinical study for prophylaxis of influenza is expected to commence in Japan in late 2009. Source: Marketwire 8/10/09

Company Discontinues Development of Breast Cancer Drug

Antisoma plc in August announced that the Phase II trial of AS1402 in breast cancer was to be discontinued. The announcement followed a meeting of the trial's data monitoring committee and a subsequent review of the data, which led the company to conclude that the trial would be very unlikely to give sufficiently positive efficacy findings. No safety concerns were identified. Antisoma has no plans for further studies of AS1402. Glyn Edwards, Antisoma's CEO, said, "While AS1402 was an early-stage product and therefore not an important contributor to our overall value, we are of course disappointed that the drug was not able to provide benefit to breast cancer patients." AS1402 (huHMFG1, previously known also as R1550 and Therex) is a humanized antibody against a form of MUC1 found on the surface of various cancers. This study was a 110-patient trial in women receiving first-line treatment for advanced breast cancer. Patients were randomized to receive either AS1402 plus the hormone therapy letrozole or letrozole alone. Letrozole will continue to be made available to patients. AS1402 was licensed by Antisoma from the Imperial Cancer Research Technologies, the technology transfer arm of the Imperial Cancer Research Fund (now Cancer Research UK). Source: Marketwire 8/7/09

Phase I Study Initiated for Nontoxigenic Clostridium Difficile

ViroPharma Inc. in August announced that dosing has begun in the Phase I clinical trial for nontoxigenic Clostridium difficile (NTCD), a novel treatment approach for preventing recurrent C. difficile infections. NTCD contains the spores of a nontoxin-producing strain of C. difficile. The study will determine the safety and tolerability of NTCD dosed orally as single and repeat escalating doses in healthy young (18-45 years of age) and older (60 years of age and older) adults. The study is being conducted in Switzerland. Should the therapy be well tolerated, the company plans to initiate NTCD repeat dosing in older adults following exposure to oral antibiotics. Antibiotic use is associated with disruption of gastrointestinal flora, which renders individuals susceptible to C. difficile colonization. The goal of NTCD dosing following antibiotic exposure is to colonize with this nontoxigenic strain of C. difficile and to prevent colonization by toxigenic strains, thereby preventing disease. Source: PRNewswire 8/6/09

Results for Potential Lung Cancer Treatment Presented at International Meeting

Threshold Pharmaceuticals, Inc. and the Virginia G. Piper Cancer Center at Scottsdale Healthcare in August announced that clinical trial results related to Threshold's clinical stage hypoxia-activated prodrug, TH-302, were presented at the World Conference on Lung Cancer in San Francisco, Calif. TH-302 is a new, novel, small molecule that is activated when cells are under conditions that lack oxygen, which is a metabolic condition characteristic of cancer cells. The presentation summarized results from two Phase I clinical trials of TH-302 evaluating safety and preliminary efficacy in patients with advanced solid tumors; one in combination with other chemotherapy agents and the other with TH-302 as monotherapy. Thirteen patients with non small cell lung cancer have been enrolled in either the combination therapy or the monotherapy clinical trial. These patients had received a median of two prior systemic therapies. Partial responses were observed in three patients, one patient receiving docetaxel and TH-302, and two patients receiving pemetrexed and TH-302. Eight of 12 (67 percent) evaluable patients achieved stable disease or better. Eight patients with small cell lung cancer were enrolled in the clinical trial evaluating TH-302 as monotherapy. These patients had received a median of three prior systemic therapies. Partial responses were observed in two patients. Enrollment in both studies continues. Source: EurekAlert! 8/6/09

MS Clinical Trial Does Not Meet Primary Endpoint

AutoImmune Inc. in late July announced that its licensee, BioMS Medical Corp., and Eli Lilly and Co. reported that dirucotide did not meet the primary endpoint of delaying disease progression, as measured by the Expanded Disability Status Scale, during a two-year Phase III trial in patients with secondary progressive multiple sclerosis (SPMS). In addition, there were no statistically significant differences between dirucotide and placebo on the secondary endpoints of the study. Lilly and BioMS also announced that they would discontinue ongoing clinical trials and review available data. Chairman of the Board and Chief Executive Officer Robert C. Bishop, PhD, stated, "We are obviously disappointed by the results and look forward to further announcements from BioMS and Lilly regarding their future plans for this approach to treating SPMS." Source: PRNewswire 7/30/09  For more information, click here.

First Patient Enrollments in Three Device Clinical Trials

Lutonix, Inc. in late July announced that patient enrollment is under way for its three simultaneous first-in-human clinical trials. The three studies are designed to test whether the proprietary Lutonix Drug Coated Balloon (DCB) catheter is safe and effective in the treatment of vascular narrowing. The PERVIDEO I registry is investigating the DCB catheter for the treatment of coronary bare metal stent in-stent restenosis. The study will assess various safety and clinical endpoints over a two-year period. Dr. Laura Mauri, associate physician and director of biometrics at Brigham & Women's Hospital in Boston, Mass., is serving as the principal investigator for the study along with coprincipal investigator Prof. Detlef Mathey of the Medical Center in Hamburg, Germany. The LEVANT I trial is a randomized study designed to test the safety and efficacy of the DCB catheter in preventing restenosis in the femoropopliteal arteries. Scheduled clinical and safety visits will assess endpoints out to two years. The study principal investigator is Prof. Dierk Scheinert, director of angiology at the Park-Krankenhaus in Leipzig, Germany. The Lutonix De Novo study will assess the interaction between bare metal stents and the DCB catheter. Safety and clinical outcome data will be collected over two years. Prof. Patrick Serruys, chief of cardiology at Erasmus Medical Center in Rotterdam, the Netherlands, is serving as study principal investigator. Source: PRNewswire 7/27/09

Company Terminates Phase III Study in Acromegalic Patients

Ambrilia Biopharma Inc. announced in July that its Board of Directors had approved the termination of a Phase III trial, Study 303, as part of ongoing measures to effectively reduce costs. Study 303 involves clinical centers in both Europe and the United States and was designed to evaluate the 30 mg, 20 mg, and 10 mg dosage forms of Ambrilia's octreotide acetate (C2L) in acromegalic patients. All patients enrolled in Study 303 reached the six-month visit, and there were no adverse effect or safety concerns. Ambrilia, through various partners, is continuing with its regulatory filings process and discussions, utilizing the results from earlier studies completed. Top-line results of Study 302, an open label extension of Study 301 in which all patients were administered C2L, were previously announced. Analysis following the 24-week extension treatment period provided longer term safety data (up to one year on C2L), as well as supportive efficacy data. A decision was recently taken not to collect further data in this group of patients. Source: Marketwire 7/24/09

Comparative Phase II Proof-of-Concept Study Initiated for Pain Therapy

QRxPharma Limited announced in July the initiation of a Phase II comparative proof-of-concept study to evaluate the efficacy and safety of MoxDuo™ IV (intravenous morphine and oxycodone) versus IV morphine alone for the treatment of moderate to severe postoperative pain in patients following hip replacement surgery. Data from this study will serve as a significant predictor of MoxDuo IV's clinical benefits and provide guidance for the design of further clinical trials leading to submission of a New Drug Application to the U.S. Food and Drug Administration within the next three years. The double-blind, active-controlled study will determine whether MoxDuo IV has fewer opioid-related adverse events than morphine alone at equianalgesic doses, and whether its maximum analgesic effect is superior to morphine alone. The study is being conducted at the Cologne-Merheim Medical Center, a part of Witten/Herdecke University, and Cologne University Hospital, both in Cologne, Germany. Following hip replacement surgery, 40 subjects will be randomised into MoxDuo IV or morphine IV groups over a two-part, 48-hour treatment period. In Part 1, rapid dosing will be used by the physician to achieve maximal reductions in pain. In Part 2, patients will manage their own pain relief on an "as needed" basis using self-administered patient controlled analgesia. QRxPharma expects the study to be completed before the end of 2009. Source: PRNewswire 7/23/09

Handheld Component of Postoperative Pain System Does Well in Phase II

AcelRx Pharmaceuticals, Inc. in July announced positive results from its first Phase II clinical study evaluating the functionality of the handheld device component of its ARX-01 Sufentanil NanoTab™ PCA System for management of acute postoperative pain in patients requiring opioid analgesia during hospitalization. Patients reliably self-administered sufentanil NanoTabs repeatedly over the 12-hour study without any ARX-01 System failures or dosing errors of any kind. This multicenter, open-label study included 30 patients (median age 68; range 51-74) undergoing elective unilateral knee replacement surgery. Patients self-administered 15 mcg doses of ARX-01 Sufentanil NanoTabs sublingually as needed using the ARX-01 handheld, with a minimal redosing interval of 20 minutes. The primary endpoint was device functionality assessed as the proportion of patients who successfully completed the study without any type of system failure. There were no system failures or dosing errors of any kind throughout the study, which included more than 375 dispensed NanoTabs. Additionally, preliminary analysis of efficacy results indicated a dropout rate due to inadequate analgesia of less than 10 percent, consistent with the superior efficacy reported for the 15 mcg dose in two earlier Phase II placebo-controlled studies. ARX-01 was well tolerated, and there were no serious adverse events related to study drug. In addition to this device functionality study, AcelRx has conducted two placebo-controlled Phase II studies of ARX-01 Sufentanil NanoTabs in patients undergoing elective unilateral knee replacement surgery and in patients undergoing major abdominal surgery. Both of those studies demonstrated highly significant efficacy results for the 15 mcg dose relative to placebo in reducing pain intensity over the 12-hour study periods. Source: PRNewswire 7/22/09

Typhoid Vaccine Proves Highly Effective in Young Children

A new study has found that a currently available, yet underused, vaccine against typhoid fever is highly effective in young children and protects unvaccinated neighbors of vaccinees. The study, conducted by the Korea-based International Vaccine Institute (IVI) in collaboration with the National Institute of Cholera and Enteric Diseases (NICED) in Kolkata, India, was published in the July 23 issue of the New England Journal of Medicine. The typhoid fever vaccine Vi polysaccharide is ideally suited to use in developing countries because it is cheap (about $.50 per dose) and requires only a single dose. Despite a recommendation by the World Health Organization for use of Vi vaccines in developing countries, its use has been limited, partly because of doubts about Vi's ability to protect preschool age children. There are also doubts about Vi's ability to confer "herd protection," or protection of unvaccinated residents living in highly vaccinated areas. To address these uncertainties, a Phase IV cluster-randomized effectiveness trial randomized 80 geographic clusters of an urban Kolkata slum to either Vi or a control vaccine. Over two years of follow-up, the Vi group was shown to have 61 percent fewer episodes of typhoid than the control group. Protection of vaccinated children under 5 years of age by Vi was even higher, at 80 percent. Interestingly, unvaccinated neighbors of Vi vaccinated persons had a 44 percent lower risk of typhoid, indicating that Vi vaccine conferred substantial herd protection. The overall level of protection among all residents of the Vi clusters, regardless of whether they were vaccinated, was 57 percent. Since the coverage of residents of the Vi clusters was about 60 percent, this observation indicates that Vi vaccine prevented as many cases of typhoid in the total population as a vaccine that was nearly 100 percent protective in vaccinated persons. The IVI-NICED study, which was supported by the Gates Foundation and the governments of Korea, Sweden, and Kuwait, also revealed that delivering the low-cost Vi typhoid vaccine is logistically and programmatically possible. Source: EurekAlert! 7/22/09

Enrollment to Begin for Phase IIb Acute Ischemic Stroke Trial

Stem Cell Therapeutics Corp. has received a No Objection Letter from the Drug Controller General of India (DCGI) to initiate a multicenter, double-blind, placebo-controlled Phase IIb acute ischemic stroke trial for its lead program, NTx®-265, and will soon begin recruiting patients in three countries. The DCGI response allows initiation of the modified REGENESIS protocol under the leadership of principle investigators Dr. Steven C. Cramer from the University of California, Irvine and Dr. Michael D. Hill of Foothills Hospital at the University of Calgary. The recruitment target for this study is nearly 130 patients. Jurisdictional approvals for the trial have also been granted in the U.S. and Canada; the Indian, U.S., and Canadian protocols share similar design, as well as safety and efficacy endpoints. NTx-265 is the company's lead therapeutic regimen of two approved and clinically well-defined drugs, human chorionic gonadotropin and erythropoietin, targeting the treatment of stroke. The twin objectives of the regimen are to stimulate the growth and differentiation of new neurons to replace the brain cells that were lost or damaged by the stroke, and importantly, to direct functional recovery of motor, visual, and cognitive capacity after acute ischemic stroke. Animal studies have shown a significant recovery in motor function after receiving the NTx-265 regimen 24 to 48 hours poststroke. Encouraging final clinical results from a completed Phase IIa stroke trial were presented at the International Stroke Conference in February, showing clinically relevant recovery in 12 of 12 patients who received the complete regimen. Source: Marketwire 7/21/09

Phase I Study Completed for Male Pattern Baldness

R-Tech Ueno, Ltd. announced in July that it has completed a Phase I clinical study on a new compound, RK-023, that is being developed as a therapeutic drug for androgenetic alopecia (male pattern baldness). The study included three arms: a patch test, a single-dose, and a five-day repeated-dose. Patch tests were conducted to obtain data on skin irritation using RK-023 preparation and a placebo on 20 healthy adult males, resulting in no adverse events. Single-dose and five-day repeated applications of RK-023 preparation to the scalp were conducted by a randomized, placebo-controlled, double-blind method to evaluate the safety and pharmacokinetics of the drug. In the single-dose study, 2 ml of RK-023 preparation was applied to the vertex region of six out of nine healthy adult males and a placebo to that of the remaining three subjects. The applied drug was spread widely covering the vertex region in order to investigate the safety in the entire body and scalp. No serious adverse events occurred. After application of the drug, blood and urine were collected in the lapse of time to determine drug concentrations. However, the drug concentration was below the quantification limit at any of the prescribed time points. In the five-day repeated-dose study, in the morning and at night 2 ml of RK-023 preparation or 2 ml of placebo was applied to six and two out of eight healthy adult males, respectively. No serious adverse event was observed during the total nine times of application up to the morning of the fifth day. When the drug concentration in the blood was measured, the level was below the quantification limit. The company intends to next start a Phase II study in Japan. Source: PRNewswire 7/21/09

Early-Phase Study Begins for Oral Anti-Inflammatory Agent

Cytokine PharmaSciences, Inc. in July announced the initiation of a Phase I study of CPSI-2364, its orally active, small-molecule inhibitor of the production of TNF-alpha and other pro-inflammatory cytokines. Results of the dose escalation and safety study in healthy volunteers are expected before the end of the year. "Based on extensive work with the predecessor compound, we believe CPSI-2364 has the potential to revolutionize the treatment of TNF-mediated diseases, such as Crohn's, rheumatoid arthritis, and psoriasis. We are excited to be advancing it into the clinic," said Dennis F. Willson, president and CEO of Cytokine PharmaSciences. "As a small molecule, CPSI-2364 is less expensive to produce than biologics and can be given orally. Moreover, because it is not a protein, CPSI-2364 is not expected to generate antibodies that could neutralize its activity and result in loss of efficacy over time." CPSI-2364 is a chemically modified form of the synthetic guanylhydrozone, semapimod. Semapimod has been shown to inhibit the signal transduction pathways that lead to the production of nitric oxide and important pro-inflammatory cytokines, including TNF-alpha, IL-1, IL-6, and IL-8. Semapimod has demonstrated activity in multiple animal models of inflammation and autoimmune disease, proof-of-concept studies that led to human clinical trials. An intravenous for