Clinical Trial Updates

The Latest Updates (Posted February 1, 2012)...

Trial Shows Drug Lowers Chronic Inflammation Measured by CRP Blood Levels

Rock Creek Pharmaceuticals, Inc., a subsidiary of Star Scientific, Inc., has completed the first successful human clinical trial showing that Anatabloc™, the dietary supplement developed by Rock Creek to provide anti-inflammatory support, lowers C-reactive protein (CRP) levels in subjects' blood. CRP is a molecule produced by the liver in response to an inflammatory signal, and is a marker for inflammation. The company in late January reported initial results from Phase II of the RCP-006 study, which consisted of 105 subjects, all of whom were smokers and 79 percent of whom were overweight or obese. Phase I of the study was a one-day trial to assess whether Anatabloc was as successful as CigRx®, the company's other dietary supplement, in reducing the urge to smoke, and results showed that CigRx and Anatabloc were equally effective. Phase II of the study was an open-label extension in which subjects continued to smoke and were instructed to take two Anatabloc tablets three times per day for two weeks. Study site visits were scheduled at the end of each one-week period so that subjects could complete study assessments and for collection of blood and breath samples. CRP levels in subjects with dose-appropriate anatabine levels were about 30 percent lower than CRP levels among those with low anatabine levels. These levels were documented despite subjects' continued smoking, and at a relatively low dose of anatabine by bodyweight in some very heavy subjects. Phase III, a longer open-label extension, is ongoing. Source: Marketwire 1/30/12

Radiopharmaceutical to Enter Prostate Cancer Trials

A new targeted radiopharmaceutical, designed to deliver a therapeutic dose of radiation directly to metastatic prostate cancer, will be manufactured in Canada to be used in clinical trials that will evaluate its efficacy and benefits for patients. The radiopharmaceutical, I-131-MIP-1466, will be manufactured by the Centre for Probe Development and Commercialization (CPDC), for the developer of the compound, U.S.-based Molecular Insight Pharmaceuticals. The initial trial, anticipated to start in early 2013, will mark the first time that a small-molecule-based radiopharmaceutical specifically targeting prostate-specific membrane antigen, a type of protein expressed in high levels on prostate tumours, will be tested for its ability to treat prostate tumours that have spread throughout the body. CPDC, a not-for-profit Centre of Excellence for Commercialization and Research, has introduced several new radiopharmaceuticals to Ontario that are now being used in clinical trials to diagnose and stage various cancers and to monitor patient response in chemotherapy trials. Molecular Insight has diagnostic radiopharmaceuticals currently in clinical development for visualizing metastatic prostate cancer, which have yielded high-quality images of lymph node and bone lesions in prostate cancer patients. I-131-MIP-1466 is a therapeutic analog of these diagnostic compounds and is radiolabeled with I-131 to enable targeted radiotherapy. Molecular Insight has demonstrated in preclinical models that I-131-MIP-1466 inhibits tumor growth in human prostate cancer xenografts. The next step is to file an Investigational New Drug application with the Food and Drug Administration in preparation for the initiation of a clinical trial. Source: PRNewswire 1/20/12

Dosing Temporarily Suspended in Trials Due to cGMP Compliance Issues

Lpath, Inc. has temporarily suspended dosing patients in its PEDigree and Nexus trials. In these trials, iSONEP™ is being tested as a treatment for wet age-related macular degeneration (Nexus) and a related complication called pigmented epithelial detachment (PEDigree). The company has taken this action because it learned from the Food and Drug Administration (FDA) that the company's fill/finish contractor, Formatech, Inc., was not in compliance with FDA's current Good Manufacturing Practice (cGMP) requirements during the period that the iSONEP clinical vials were filled. Accordingly, even though Lpath believes it has taken appropriate steps to oversee Formatech's manufacturing in order to ensure product quality, it has suspended dosing as a precaution to ensure the continued safety of all patients in its clinical trials. iSONEP was well tolerated by all patients in the Phase I trial and by all patients thus far in the PEDigree and Nexus trials. The company has received no claims raising safety concerns regarding iSONEP. Lpath has initiated the process to manufacture additional drug substance and has identified an alternate fill/finish contractor. Lpath plans to resume dosing in both clinical trials within four to six months, subject to any necessary regulatory approvals. The FDA has agreed to respond within 30 days upon Lpath's request to reinstate dosing. Source: Marketwire 1/26/12

First Patients Dosed in Phase Ib Cellulite Study

Auxilium Pharmaceuticals, Inc. in January announced that the first cohort of patients has been dosed in its Phase Ib trial of Xiaflex® (collagenase clostridium histolyticum) for the treatment of edematous fibrosclerotic panniculopathy (EFP), commonly known as cellulite. Cellulite has been reported to occur in 85 to 98 percent of postpubertal females and rarely in men. The condition is prevalent in women of all races. Cellulite is described as a localized metabolic disorder of tissue under the skin, which can involve the loss of elasticity or shrinking of collagen cords, called septae, that attach the skin to lower layers of muscle. When fat in cellulite prone areas swells and expands, the septae tether the skin, which causes surface dimpling characteristic of cellulite. Xiaflex treatment is intended to target and lyse, or break, those collagen tethers with the goal of releasing the skin dimpling and potentially resulting in smoothing of the skin. The single-site, open-label, dose-escalation study is targeted to enroll 63 women between 21 and 60 years of age. The objectives of the study are to assess the safety, effectiveness, and pharmacokinetics of Xiaflex for the treatment of EFP. Topline results are expected in the second half of 2012. Subjects will receive 10 concurrent injections (0.1 or 0.5 mL per injection) of Xiaflex via a standardized template over a targeted area (8 cm x 10 cm) of EFP. The total dose that will be administered into the targeted area will range between 0.0029 mg and 0.116 mg; these doses represent between 0.5 percent and 20 percent of the dose used in a single injection for Dupuytren's contracture (0.58 mg). Safety will be evaluated through the collection of adverse events, as well as a targeted assessment of local reactions to the treatment. The treatment effectiveness will be evaluated by investigator and patient assessments, as well as 3-D photographic imaging techniques. Source: PRNewswire 1/26/12

Company Receives IDE Approval to Begin Pivotal Trial for Surgical Adhesive

Cohera Medical, Inc.® announced in January that it has received Investigational Device Exemption (IDE) approval from the U.S. Food and Drug Administration (FDA) to begin a prospective, multicenter, randomized clinical trial for its lead product, TissuGlu® Surgical Adhesive in the United States. The study will investigate the effectiveness of TissuGlu and its effect on wound drainage and associated complications in abdominoplasty surgeries. There are currently no medical devices approved by the FDA, or in pivotal clinical trials, for a synthetic adhesive indicated for approximation of tissues in large flap surgeries. Initiation of the study is planned in the first quarter of 2012 and will be conducted at five clinical sites with 150 patients, and upon favorable conclusion will allow the company to complete a Pre-Market Approval application for TissuGlu with the FDA. Cohera Medical recently received CE Marking approval for TissuGlu and began selling product to hospitals and surgeons in Germany. The company plans to expand the commercial availability of TissuGlu to additional European markets in early 2012. Source: PRNewswire 1/24/12

Skin Cancer Detection Device Offers Diagnostic Accuracy, Helps Reduce Biopsies

Verisante Technology, Inc. in January announced the results of the statistical analysis completed by the University of British Columbia on data from a clinical study in which the Verisante Aura was used. The Aura™ is a noninvasive optical system designed as a tool to aid medical professionals in the assessment of suspect skin lesions for diagnosis as either skin cancer or a benign disorder. It uses Raman spectroscopy to biochemically analyze the skin, providing immediate results. In the study, measurements on more than 1,000 lesions were acquired from 848 patients. The analysis presented here is focused specifically on malignant melanoma, squamous cell carcinoma, basal cell carcinoma, actinic keratosis, and benign conditions that can visually mimic skin cancer. The final dataset thus consisted of 518 validated lesions from 453 subjects. The results of the analysis showed that Aura had a sensitivity of 99 percent with a specificity of 17 percent in differentiating all major skin cancers from benign lesions. At a sensitivity of 95 percent, Aura's specificity increased to 41 percent. For melanoma versus benign lesions, Aura had a sensitivity of 99 percent with a specificity of 15 percent. At a sensitivity of 95 percent, specificity increased to 38 percent. The Food and Drug Administration has previously required an endpoint sensitivity of 95 percent for a device that detects melanoma. Approved for sale in Canada, Europe, and Australia, Verisante's Aura is indicated for use for the evaluation of skin lesions that may be clinically suspicious for melanoma, squamous cell carcinoma, and/or basal cell carcinoma when a medical professional chooses to obtain additional information to rule out one of the above conditions before making a final decision to biopsy. Source: Marketwire 1/23/12

Patient Enrollment Initiated in Phase III Trial to Prevent Breast Cancer Recurrence

Galena Biopharma, Inc. in January announced the initiation of its Phase III PRESENT trial for NeuVax™ (E75 peptide plus GM-CSF) vaccine in HER2 1+ and 2+ breast cancer patients (often referred to as HER2 negative) in the adjuvant setting to prevent recurrence. The PRESENT study is a randomized, multicenter, multinational clinical trial that will enroll approximately 700 breast cancer patients. The trial design has been updated to include current National Comprehensive Cancer Network guidelines and recently received Special Protocol Assessment concurrence from the U.S. Food and Drug Administration (FDA). Based on a successful Phase II trial, which achieved its primary endpoint of disease-free survival, the FDA has agreed that the design and planned analysis of the Phase III study adequately address the objectives necessary to support an acceptable regulatory submission for marketing approval. The trial will be conducted in adjuvant breast cancer patients who are node positive, have an HLA status of A2/A3+, and have low or intermediate HER2 expression. These patients are not eligible to receive Herceptin® (trastuzumab, marketed by Roche-Genentech) therapy that is currently approved only for patients with high HER2, or 3+ expression. Once qualified patients have achieved a complete response from current standard-of-care treatment (surgery, radiation, and/or chemotherapy), they will be randomized and dosed with either NeuVax or control (placebo plus GM-CSF). Patients will receive one intradermal injection every month for six months, followed by a booster inoculation every six months thereafter. The primary endpoint is disease-free survival at three years or 139 events (recurrence of cancer). A data safety monitoring board will conduct an interim analysis for safety and futility after 70 events. Galena is currently on track for the initiation of approximately 100 investigator sites in the U.S. and abroad. Source: Globe Newswire 1/20/12

Trial Confirms Drug's Activity in Patients with Advanced Gastric Cancer

Genta Inc. in January announced results from its Phase IIb, confirmatory clinical trial of tesetaxel in patients with advanced gastric cancer. The trial is lead by investigators from M.D. Anderson Cancer Center in Houston, Texas, in collaboration with Northwestern University in Chicago, Ill., the University of Pennsylvania in Philadelphia, and the Severance Hospital in Seoul, South Korea. The study has enrolled 41 patients who progressed on at least one prior chemotherapy regimen that included a platinum compound (cisplatin, oxaliplatin, or carboplatin) and a fluoropyrimidine compound (5-fluorouracil [5-FU] or capecitabine [Xeloda®; Hoffman-La Roche, Inc.]). Two patient cohorts were treated over a range of "flat" (as opposed to "weight-based") doses starting at 40 to 45 mg (Cohort 1) and 50 to 60 mg (Cohort 2), whereas Cohort 3 used weight-based dosing at the maximally tolerable dose (MTD) of 27 mg/m2. Doses were repeated every three weeks, and overall response rate (ORR) was the trial's primary endpoint. The ORR in Cohort 3, which remains open to accrual, was 20 percent in patients treated with tesetaxel as second-line therapy. Body weight variation resulted in under-dosing relative to the MTD in Cohorts 1 and 2, which yielded ORRs of 8 percent and 15 percent, respectively. Median survival has not been reached in Cohort 3, whereas median survival in Cohorts 1 and 2 was 7.6 and 7.5 months, respectively. Overall survival is the primary endpoint in planned Phase III studies of tesetaxel in gastric cancer. "These new data confirm the activity of tesetaxel in patients with advanced gastric cancer at levels that are at least equivalent to studies of docetaxel in this population," said Dr. Loretta M. Itri, Genta's president for pharmaceutical development and chief medical officer. "Data from two multicenter trials support the decision to undertake our planned Phase III trial of tesetaxel as second-line therapy in patients with advanced gastric cancer." Source: Globe Newswire 1/19/12

Drug Improves Survival of Colorectal Cancer Patients

An investigational drug called regorafenib slowed the progression of tumors and lengthened the lives of patients with metastatic colorectal cancer, an international Phase III clinical trial found. The findings were presented in January at the Gastrointestinal Cancers Symposium of the American Society of Clinical Oncology in San Francisco, Calif. by Mayo Clinic oncologist Axel Grothey, MD, principal investigator of the trial in the United States. "For years, patients with metastatic colorectal cancer have faced a devastating impasse when standard chemotherapies have failed to halt the growth of tumors and physicians have run out of effective drugs to offer them," says Grothey. "This is the first novel agent in eight years to show improvement in overall survival of colon cancer patients who have run out of treatment options." Researchers tested regorafenib in the randomized, placebo-controlled trial, conducted simultaneously in the United States, Europe, Japan, Australia, and China. They looked at survival outcomes in 760 patients whose cancer had progressed despite standard chemotherapy regimens. Regorafenib is a multikinase inhibitor, which has the effect of slowing cell proliferation and blood vessel growth and tempering a variety of biological pathways that are activated in tumors. Researchers found that patients with metastatic colon cancer who were treated with the drug showed a 29 percent increase in overall survival when compared to those treated with placebo. The median length of survival for patients treated with the drug increased from five months to six and-a-half months, a statistically significant jump. Overall, regorafenib reduced patients' risk of dying from cancer during the trial by 23 percent. The trial, whose largest group of study participants in the United States was at Mayo Clinic, finished more than a year ahead of schedule. Grothey's research was sponsored by Bayer Healthcare. Source: EurekAlert! 1/17/12

Earlier Updates...

Results from Phase III Alzheimer's Trial Disappoint

Medivation, Inc. and Pfizer Inc. in January announced results from the CONCERT trial, which is a Phase III trial that evaluated dimebon (latrepirdine) when added to ongoing treatment with donepezil HCL tablets in patients with mild-to-moderate Alzheimer's disease. Dimebon did not achieve statistically significant results for either of the two co-primary endpoints, the Alzheimer's Disease Assessment Scale-cognitive subscale, which measures cognitive ability, or the Alzheimer's Disease Cooperative Study-Activities of Daily Living, which measures self care and daily function. Medivation and Pfizer will discontinue development of dimebon for all indications and will terminate the ongoing open-label extension study in Alzheimer's disease. The companies also announce that they will terminate their collaboration to co-develop and market dimebon pursuant to the terms of their Collaboration Agreement. CONCERT was a 12-month global randomized, double-blind, placebo-controlled trial that enrolled 1,003 patients with Alzheimer's disease. Patients on a stable dose of donepezil for at least four months were randomized to one of three treatment groups: dimebon 20 mg three times per day, dimebon 5 mg three times per day, or placebo. Source: Marketwire 1/17/12

Trials Highlight Difficulties in Treating Migraines

Acupuncture and sham acupuncture appear equally effective in treating migraines, according to a clinical trial published in the Canadian Medical Association Journal. An international team of researchers conducted a randomized controlled trial to determine the effect of acupuncture compared to sham acupuncture in treating migraines in 480 patients at nine hospitals in China. The patients were randomly assigned to four groups, including one sham acupuncture group and three groups receiving different types of acupuncture. About half to three-quarters of people with migraines were better after acupuncture and sham acupuncture after 16 weeks. "Acupuncture has a large effect on treating migraines, but the specific therapeutic effect may be minor," state the authors. In a second randomized controlled trial, researchers in the Netherlands looked at whether a proactive approach by primary care physicians to patients with suboptimal migraine treatment would result in improvements. They enrolled 490 patients from 64 general practices (233 patients who attended consultations to evaluate treatment of their migraines and 257 patients in the control group). The researchers found no clinically relevant effect of a proactive approach to migraine in primary care for patients who were using two or more doses of triptan per month. Source: EurekAlert! 1/9/12

Nicotine Patch Shows Benefits in Mild Cognitive Impairment

Using a nicotine patch may help improve mild memory loss in older adults, according to a study published in the January 10 print issue of Neurology. The study involved 74 people with an average age of 76 who had mild cognitive impairment and were not smokers. Half of the participants received a nicotine patch of 15 mg per day for six months and half received a placebo. The participants took several tests of memory and thinking skills at the start of the study and again after three and six months. After six months of treatment, the nicotine-treated group regained 46 percent of normal performance for age on long-term memory, whereas the placebo group worsened by 26 percent over the same time period. Nicotine stimulates receptors in the brain that are important for thinking and memory skills. People with Alzheimer's disease lose some of these receptors. The study was supported by the National Institute on Aging and the National Institute of General Medical Sciences. Pfizer Inc. provided the transdermal nicotine patches. Source: EurekAlert! 1/9/12

Combination Therapy Shows Positive Response for Children with ADHD

While pharmacologic agents have a demonstrated efficacy in children with attention-deficit/hyperactivity disorder (ADHD), some children have suboptimal response to a single pharmacologic agent. A recent study published in the January 2012 issue of the Journal of the American Academy of Child and Adolescent Psychiatry is the first randomized placebo-controlled trial designed to assess efficacy and safety of guanfacine extended release (GXR) as an adjunct to psychostimulants in children and adolescents diagnosed with ADHD who had a suboptimal response to a psychostimulant alone. The nine-week multicenter, double-blind, placebo-controlled, dose-optimization study involved participants in 59 study sites who continued their stable dose of psychostimulant given in the morning and were randomized to receive GXR in the morning, GXR in the evening, or placebo. For both morning and evening administration of GXR, subjects receiving GXR plus a psychostimulant showed significantly greater improvement from baseline to endpoint, as measured by the ADHD-Rating Scale IV total score, compared to subjects receiving placebo plus a psychostimulant. This study was supported by Shire Development Inc. Source: EurekAlert! 1/9/12

Phase IIb Safety and Efficacy Studies of COPD Combination Treatment Completed

Pearl Therapeutics Inc. in January announced the completion of two Phase IIb clinical studies of PT003, the company's investigational inhaled combination bronchodilator product for the treatment of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). The first of these two trials (NCT01349803) was a 237-subject cardiovascular safety study designed to measure the change in mean heart rate following twice-daily chronic administration of the combination PT003, and its components PT001 and PT005. The second trial (NCT01349816) was a 185-patient, randomized, double-blind, dose-confirmation study of different doses of PT003 compared to its components. PT003, PT001, and PT005 were shown to be safe, effective and well tolerated, with no meaningful changes in heart rate or other cardiovascular safety parameters relative to baseline as measured by Holter monitor over two weeks. Pearl plans to present results of these trials at appropriate medical meetings in 2012. Source: PRNewswire 1/6/12

Phase III Study Initiated in Patients with Anterior Uveitis

EyeGate Pharma announced in January that it has enrolled the first patient in a milestone Phase III pivotal study of its lead product EGP-437 (a late-stage asset with multiple indications for inflammatory ocular indications), for the treatment of anterior uveitis, at Tauber Eye Center in Kansas City, Mo. The randomized, double-masked, positive-controlled, noninferiority study will enroll up to 200 subjects at more than 20 U.S. sites in order to assess the effectiveness of EGP-437 in comparison to topically applied prednisolone acetate eye drops. EGP-437 will be administered using the EyeGate® II Drug Delivery System, a noninvasive iontophoretic drug delivery technology. The company's Phase II study results appear in the January 2012 issue of Ophthalmology, and reveal that approximately two-thirds of the patients reached an anterior chamber cell score of zero within 28 days, after only receiving one iontophoresis treatment. Source: Marketwire 1/5/12

Trial Demonstrates that Drug Significantly Reduces Gout Flares

A Phase II clinical trial found that rilonacept, an inhibitor of the protein interleukin-1 (IL-1), significantly reduced acute gout flares that occur when initiating uric acid-lowering therapy. Results of the trial—the first placebo-controlled study investigating IL-1 targeted therapy in prevention of gout flares—show rilonacept to be generally well tolerated with no serious infections or treatment-related serious adverse events reported. Full findings are published in Arthritis & Rheumatism. Rilonacept—marketed under the brand name Arcalyst® to treat another disease—is designed to neutralize the protein IL-1 before it produces signals that can trigger inflammation. Thus, researchers looked to test the effectiveness of rilonacept in preventing gout flares and enrolled 83 patients at 27 study centers across the U.S. for the Phase II trial, randomized in a double-blind fashion, with 41 administered rilonacept via subcutaneous injection (a double dose [320 mg] followed by 160 mg weekly for 16 weeks), and 42 administered weekly placebo. All patients were started on allopurinol (300 mg/day) to reduce uric acid levels. Trial results revealed a significantly lower number of gout flares in participants taking rilonacept, with only six flares in the rilonacept arm compared to 33 in the placebo group. Source: EurekAlert! 1/5/12

First-in-Class Treatment Improves Lactose Issues in Phase II Trial

Ritter Pharmaceuticals, Inc. in January announced positive results from its Phase II study of RP-G28, the first-in-class treatment of lactose intolerance. Treatment was shown to improve digestive symptoms associated with lactose intolerance, including abdominal pain. Importantly, the reduction of breath hydrogen production after a lactose load was measured, providing evidence of a clinically meaningful biological effect. This study represents the first adequate and well-controlled Phase II study for a prescription drug candidate for patients with lactose intolerance. Subjects in the RP-G28 group reported a reduction in total symptoms of 56 percent after treatment, which increased to nearly a 70 percent reduction by 30 days post-treatment. Subjects had a statistically significant decrease in abdominal pain compared to those receiving placebo, consistent with the improvement in hydrogen breath test results following post-treatment lactose challenge as compared to baseline (pre-treatment) results. Subjects treated with RP-G28 had a 15 percent greater decrease in hydrogen production as compared to those receiving placebo. Ritter Pharma plans to release the complete data set for the trial at an upcoming major medical meeting or in a peer-reviewed journal. Source: Marketwire 1/5/12

FDA Approves Launch of Huntington's Disease Clinical Trial

Prana Biotechnology in January announced that it has received approval from the U.S. Food and Drug Administration (FDA) to start recruiting patients for the company's first clinical trial using PBT2 in patients with Huntington's disease (HD). The company has appointed the Huntington Study Group to coordinate the Phase II trial. The group will commence recruitment of patients for the trial, named Reach2HD, at clinical sites across the U.S. and in Australia. The randomized, double-blind, placebo-controlled trial will enroll 100 patients with early to mid-stage Huntington's disease. The principal investigator on the study is Dr. Raymond Dorsey of Johns Hopkins University Medical Center. Prana aims, in this trial, to demonstrate safety, motor benefits, and the same cognitive benefits for Huntington's patients that it has already demonstrated in Alzheimer's patients treated with PBT2. Source: Marketwire 1/4/12

Patient Enrollment and Device Implantation Completed in Obesity Trial

EnteroMedics Inc. in late December announced that it has completed enrollment and device implantation in its ReCharge pivotal trial for obesity. A total of 233 patients have been successfully implanted at 10 clinical sites in the U.S. and Australia. The ReCharge trial is a randomized, double-blind, parallel-group, multicenter pivotal study testing the effectiveness and safety of VBLOC® vagal blocking therapy, delivered via EnteroMedics' Maestro® Rechargeable System, in the treatment of obesity. VBLOC therapy is a first-in-class weight loss treatment designed to control both hunger and fullness by regulating the primary nerve that controls the digestive system. It is designed to be minimally invasive and to address the lifelong challenge of obesity by empowering the individual to take positive steps along a path toward weight loss without compromising their anatomy or lifestyle. The company has begun a 12-month blinding period in the trial in continuation of its plans for U.S. registration. All patients in the study received an implanted device and were randomized in a 2:1 allocation to treatment or control groups. The control group received a nonfunctional device during the study period. All patients are expected to participate in a weight management counseling program. Source: Marketwire 12/28/11

Major Depressive Disorder Trial Receives Approval to Advance to Phase Ib

Neuralstem, Inc. in December announced that it has been approved by the Food and Drug Administration to advance to Phase Ib in its ongoing clinical trial to test its novel neuroregenerative compound, NSI-189, for the treatment of major depressive disorder (MDD). Phase Ib will test the safety and tolerability of the drug in depressed patients. NSI-189 is a proprietary new chemical entity discovered by Neuralstem that stimulates new neuron growth in the hippocampus, an area of the brain that is believed to be involved in MDD as well as other diseases and conditions, such as Alzheimer's disease and post-traumatic stress disorder. The NSI-189/MDD trial is a randomized, double-blind, placebo-controlled, multiple-dose escalating trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamic effect of NSI-189 in the treatment of MDD. Phase Ia tested escalating doses of single administration of NSI-189 in healthy patients. Phase Ib will test the safety of escalating doses of NSI-189 for 28 daily administrations in 24 depressed patients. The Phase Ib portion of the trial is expected to take approximately six months to complete. Source: EurekAlert! 12/27/11

Topline Results Announced for Transdermal Treatment of Osteoporosis

Radius Health, Inc. in December announced positive results from a Phase Ib clinical study to evaluate the transdermal BA058 microneedle patch. BA058 is the company's novel anabolic (bone-building) drug for the treatment of osteoporosis currently also undergoing Phase III evaluation as a daily subcutaneous injection. The patch is Radius' short wear-time, transdermal form of BA058 based on 3M Drug Delivery Systems' Solid Microstructured Transdermal Systems microneedle technology platform. The successful trial demonstrated the ability of the patch to safely and rapidly deliver BA058 over a short wear-time, with no increased exposure resulting from longer wear, as well as supportive biochemical evidence of bone-building activity following seven days of dosing. The trial was a randomized, double-blind, placebo-controlled study designed to assess the pharmacokinetic (PK) profile, safety, and tolerability of single and multiple doses of BA058 delivered transdermally via microneedle patch. The trial also evaluated wear-time and administration site tolerability compared to BA058 subcutaneous injection. The study was conducted on 74 otherwise healthy postmenopausal women from 50 to 80 years of age who received at least one daily dose of the BA058 Microneedle Patch, placebo, or BA058 injection. The patch was shown to be safe and well-tolerated in all doses studied, consistent with results from Phase I and II studies of the company's injectable product, and demonstrated a suitable PK profile relative to injection. Source: Marketwire 12/21/11

Phase III Development Launched for Gout Treatment

Ardea Biosciences, Inc. in December announced that it has initiated the first of four planned Phase III clinical trials in its development program for lesinurad, the company's lead product candidate for the chronic treatment of gout. The development program is expected to involve approximately 2,000 gout patients at sites around the world. The remaining Phase III studies in the program are expected to begin shortly. Lesinurad is an oral, once-daily inhibitor of the URAT1 transporter in the kidney that regulates uric acid excretion from the body. Lesinurad has been evaluated as a single agent and in combination with the approved xanthine oxidase inhibitors, allopurinol and febuxostat. More than 700 people have received lesinurad in Phase I and II clinical trials. Source: Marketwire 12/19/11

Phase II Trial Shows Drug Reduces Spread of Nasopharyngeal Carcinoma

Combining the widely used anticancer drug bevacizumab with standard chemoradiation therapy is safe and could prolong survival in patients with advanced nasopharyngeal carcinoma, according to a new Phase II trial published online in The Lancet Oncology in December. The results indicate that bevacizumab might be more effective at preventing the spread of nasopharyngeal carcinoma to other parts of the body, the most common cause of death in patients with advanced disease. Principal investigator Nancy Lee, MD, of Memorial Sloan-Kettering Cancer Center in New York, and colleagues report the new combination treatment resulted in more than 90 percent of patients surviving two years with no distant metastases and in 75 percent of patients not getting worse. Treatment with bevacizumab increased the overall likelihood of patients surviving two years or more, compared to findings from previous studies of chemoradiation alone. At two years, an "unexpectedly high" number (91 percent) of patients were still alive. The study included 46 previously untreated patients with locoregionally advanced nasopharyneal carcinoma from 19 Radiation Therapy Oncology Group (RTOG) member centers in North America and Hong Kong. Bevacizumab was added to the concurrent and adjuvant phases of chemotherapy with cisplatin and fluorouracil. The trial was funded by grants to RTOG the from the U.S. National Cancer Institute. Source: EurekAlert! 12/16/11

New Device May Help Patients with Peripheral Artery Disease

Good Samaritan Hospital in Los Angeles, Calif., is participating in the Levant 2 clinical trial to investigate a potential new treatment option for people with peripheral artery disease (PAD). The clinical trial will help doctors determine whether a drug-coated angioplasty balloon made by trial sponsor Lutonix will be more successful in keeping narrowed arteries open for longer compared to treatment with a noncoated standard angioplasty balloon. PAD is a disease in which plaque builds up in the arteries that carry blood to the head, organs, and limbs. PAD usually affects the arteries in the legs, but it can also affect arteries that carry blood from the heart to the head, arms, kidneys, and stomach. Many people who have PAD have no signs or symptoms. Others may experience difficulty when walking or climbing stairs, among other symptoms. Treatment for PAD focuses on reducing symptoms, preventing further progression of the disease, and, in most cases, lifestyle changes, exercise, and claudication medications that can help slow the progression or even reverse the symptoms of PAD. If the paclitaxal-coated balloon under investigation in the Levant 2 trial demonstrates an ability to significantly reduce arterial renarrowing, it could establish a very significant change in the treatment of peripheral artery disease for potentially millions of patients. Patients considered for enrollment in the clinical trial are screened using an ultrasound test to assess the degree of narrowing and blood flow to the legs. Source: PRNewswire 12/15/11

First Patient Inoculated in Phase I/II Trial for HIV/AIDS Therapeutic Vaccine

GeoVax Labs, Inc. in December announced that the first patient has been inoculated in the Phase I/II clinical trial for the company's HIV/AIDS therapeutic vaccine. This is the first study using GeoVax Labs' vaccines for the treatment of persons who are HIV infected. The protocol for the trial will carefully monitor safety while evaluating the ability of the vaccine to elicit protective immune responses in vaccinated participants. The trial is based on the achievement of postvaccine viral control in animal studies conducted in recently infected nonhuman primates at the Yerkes National Primate Research Center, affiliated with Emory University. The AIDS Research Consortium of Atlanta, Ga., the Alabama Vaccine Research Center at the University of Alabama, Birmingham, and the AIDS Research Alliance of Los Angeles, Calif., are participating in the trial, and are actively seeking persons who are interested in and fit the criteria for the study. To be eligible for the study, persons should have started drugs within 18 months of their last HIV negative test. Persons who have been infected within the past 18 months, but not started drugs, are also eligible for recruitment into the study. The first participant was enrolled at the AIDS Research Consortium of Atlanta. Source: PRNewswire 12/13/11

Phase I Data Demonstrate Drug Reduces Factor XI Activity Without Bleeding

Isis Pharmaceuticals, Inc. in December announced that positive results from a Phase I study with ISIS-FXIRx demonstrated that treatment with ISIS-FXIRx produced dose-dependent, statistically significant reductions of up to 78 percent in Factor XI activity. ISIS-FXIRx was safe and well tolerated with no increase in bleeding. High levels of Factor XI increase the risk of aberrant blood clot formation (thrombosis) that is responsible for most heart attacks and strokes. Elevated levels of Factor XI also increase the risk of venous thrombosis, a common problem after surgery, particularly major orthopedic procedures. Although currently available anticoagulants (blood thinners) reduce the risk of these complications, they are associated with increased bleeding that can be fatal. Factor XI is a unique target for new blood-thinning therapies because Factor XI plays a key role in clot formation, but its inhibition does not induce bleeding. Consequently, Factor XI-targeted therapy holds the promise of reducing thrombosis with a potentially better safety profile than currently available anticoagulants. The Phase I study in healthy volunteers was a double-blind, randomized, placebo-controlled, dose-escalation trial designed to assess the safety and pharmacokinetic profile of ISIS-FXIRx and to assess the initial effects of the drug on Factor XI activity as measured with an assay that employs activated partial thromboplastin time (aPTT), a common measure of clotting time. ISIS-FXIRx was evaluated in single and multiple doses ranging from 50 mg per week up to 300 mg per week. Robust, sustained, statistically significant reductions of up to 78 percent and 85 percent in Factor XI protein levels were seen in the 200 mg and 300 mg dose cohorts, respectively. Robust, sustained, statistically significant reductions of up to 71 percent and 78 percent in Factor XI activity were seen in the 200 mg and 300 mg dose cohorts, respectively. Reductions in activity were accompanied by aPTT prolongation, consistent with preclinical data. Source: PRNewswire 12/12/11

Breast Cancer Drug Promising as Part of Combo Treatment in Phase II

Puma Biotechnology, Inc. in December announced results from several clinical trials of Puma's investigational drug PB272 (neratinib). A Phase I/II trial of PB272 given in combination with the chemotherapy drug capecitabine was conducted at numerous locations in the United States, Europe, and Asia. The trial was sponsored by Pfizer and the Phase I results of this trial were previously presented last year. The Phase II portion of the study enrolled patients with confirmed ErbB2+ (HER2+) metastatic or locally advanced breast cancer, and documented disease progression following prior treatment with trastuzumab and taxane chemotherapy. Patients were administered PB272 at a dose of 240 mg per day in combination with capecitabine given at a dose of 1,500 mg/m2 (750 mg/m2 twice daily) on Days 1 to 14 of each 21-day cycle. The results of the study showed that the combination of PB272 and capecitabine had acceptable tolerability. The efficacy results from the trial showed that for the 61 patients in the trial who had not been previously treated with the HER2 targeted agent lapatinib, seven (11 percent) experienced a complete response, 32 (52 percent) experienced a partial response, and five (8 percent) experienced stable disease for greater than six months, which translates to an overall response rate of 64 percent and a clinical benefit rate of 72 percent. In addition, for the seven patients in the trial who had previously been treated with lapatinib, one (14 percent) experienced a complete response, three (43 percent) experienced a partial response, and one (14 percent) experienced stable disease for greater than six months, which translates to an overall response rate of 57 percent and a clinical benefit rate of 71 percent. The median progression-free survival (PFS) for patients who had not received prior treatment with lapatinib was 40.3 weeks and the median PFS for the patients who had received prior lapatinib treatment was 35.9 weeks. In a separate randomized Phase II study, PB272 was given as monotherapy versus lapatinib given in combination with capecitabine at sites in the United States, Europe, and Asia. The trial was sponsored by Pfizer. In the trial, patients who had confirmed HER2+ metastatic or locally advanced breast cancer and disease progression following prior treatment with trastuzumab and taxane chemotherapy were enrolled. Patients were randomized to receive either PB272 given as monotherapy daily at a dose of 240 mg per day or lapatinib given daily at a dose of 1,250 mg per day in combination with capecitabine given at a dose of 2,000 mg/m2 (1,000 mg/m2 twice daily) on Days 1 to 14 of each 21-day cycle. The efficacy results from the trial showed that for the 117 patients in the neratinib monotherapy arm of the trial, 2 percent experienced a complete response, 27 percent experienced a partial response, and 15 percent experienced stable disease for greater than six months, which translates to an overall response rate of 29 percent and a clinical benefit rate of 44 percent. For the 116 patients in the trial treated with the combination of lapatinib and capecitabine, 4 percent experienced a complete response, 36 percent experienced a partial response, and 23 percent experienced stable disease for greater than six months, which translates to an overall response rate of 40 percent and a clinical benefit rate of 63 percent. The median PFS for patients in the neratinib monotherapy arm was 4.5 months and the median PFS for the patients who had received the combination of lapatinib and capecitabine was 6.8 months. A third Phase I/II clinical trial, involving PB272 given in combination with the chemotherapy drug temsirolimus, was conducted at Memorial Sloan-Kettering Cancer Center. The trial was sponsored by Pfizer and the Phase I results of this trial were previously presented last year. The Phase II portion of the study enrolled patients with either HER2+ metastatic breast cancer and disease progression on trastuzumab or with triple negative breast cancer. Patients in the study received a median of three prior cytotoxic regimens (range one to 12 prior regimens). Patients in the HER2+ cohort of the trial received a median of two prior trastuzumab containing regimens (range one to nine prior regimens). Patients were administered PB272 at a dose of 240 mg per day in combination with temsirolimus given at a dose of 8 mg weekly. The results of the study showed that the combination of PB272 and temsirolimus had acceptable tolerability. The efficacy results showed that for the 15 patients with HER2+ disease, nine (60 percent) experienced a partial response and one (7 percent) experienced stable disease for greater than six months, which translates to a clinical benefit rate of 67 percent. Patients who experienced a partial response to the combination of neratinib plus temsirolimus demonstrated a maximum change in the size of their target lesions of between 33 percent and 83 percent. None of the five patients with triple negative breast cancer demonstrated a partial response or stable disease for greater than six months. Source: PRNewswire 12/9/11

First Genome Sequencing Trial for Triple Negative Cancer Points to New Treatments

Initial results from an ongoing clinical trial, the first designed to examine the utility of whole-genome sequencing for triple negative breast cancer, were reported in December during the CRTC-AACR San Antonio Breast Cancer Symposium. The results indicate activation of targets not previously associated with triple negative disease, and could point toward new treatment strategies. Based on mutations uncovered by sequencing, physicians recommended the women enter treatment protocols for either existing drugs or new agents being evaluated in clinical trials sponsored by pharmaceutical companies. Triple negative breast tumors, which make up nearly 20 percent of breast cancers, do not respond to treatment with targeted therapies such as Herceptin® (trastuzumab). Of 11 tumors sequenced to date, each was genomically unique, but commonalities were observed. Some patients displayed amplified genes in the RAS pathway; one patient had amplification of the BRAF oncogene, as well as activation of a growth pathway known as the MEK/AKT pathway. This patient displayed an impressive response to a MEK/AKT inhibitor currently in a Phase I clinical study. "Those results are quite striking, considering that these are women with advanced disease," said Joyce O'Shaughnessy, MD, who presented the data. "If MEK/AKT activation is found to be present in a substantial fraction of triple negative patients, inhibitors of this pathway could prove a significant tool in fighting this disease." O'Shaughnessy is medical director and cochair of the Breast Cancer Research Committee, US Oncology Research; a practicing oncologist with Texas Oncology; and the Celebrating Women Chair of Breast Cancer Research at Baylor Charles A. Sammons Cancer Center. "This is among the largest studies of a single tumor type in which whole genome sequencing is being used to identify potential options for targeted treatment," said John Carpten, PhD, director of the Integrated Cancer Genomics Division at the Translational Genomics Research Institute (TGen). "As the field of genomic medicine matures, this study is sure to provide key early insights into how sequencing can best be utilized in the clinic." Source: EurekAlert! 12/8/11

Anti-Estrogen Combo Better than Single Drug for Hormone-Sensitive Breast Cancer

Postmenopausal women with hormone receptor-positive metastatic breast cancer may have a new treatment option that could lengthen their lives, according to results of a study by the SWOG clinical trials network that were presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium. The combination of the two anti-estrogen drugs anastrozole and fulvestrant used in the SWOG S0226 trial extended the median survival time of women with breast cancer by more than six months compared to those who underwent standard treatment with anastrozole alone (47.7 months versus 41.3 months). The combination therapy also lengthened the median time to disease progression (15 months versus 13.5 months). Lead study coordinator Rita Mehta, MD, of the University of California, Irvine Medical Center, says the results of the Phase III trial are particularly exciting because "these patients have not had a new treatment that gave them an overall survival benefit in more than a decade." Anastrozole (Arimidex®) and fulvestrant (Faslodex®) are both already used in treating breast cancer, though not in combination. The former reduces the production of tumor-promoting estrogen, while the latter interferes with the receptors that allow estrogen to signal cells to grow and reproduce. Researchers think it is these two different modes of action together that make the combination so effective against hormone receptor-positive breast cancer, the subtype that accounts for more than half of all breast cancers. "If we take away estrogen and the estrogen receptor, the two together should be better than just doing one at a time," says Mehta. Starting in the spring of 2004, she and colleagues at 72 other institutions enrolled 707 postmenopausal women with metastatic hormone receptor-positive breast cancer to the trial. Women were assigned at random to one of the study's two arms. Patients on both arms got a standard 1 mg oral daily dose of anastrozole. Those on the combination arm also got a 250 mg injection of fulvestrant every 28 days, after an initial set of injections to raise the level of fulvestrant in their bloodstream. Researchers saw no significant differences in how well patients tolerated the two therapies. The overall survival benefit was particularly strong in women who had not previously had tamoxifen therapy for their breast cancer. Among this tamoxifen-naive group (about 60 percent of patients in each arm), median overall survival time on the combination therapy was 47.7 months as compared to 39.7 months for those taking only anastrozole. The trial researchers are hesitant, however, to focus too much attention on this aspect of the findings. Because plans to analyze the results by prior tamoxifen use were not built into the original trial design, the results of that analysis must clear a higher bar to be found statistically significant. Funding for the trial came primarily from the National Cancer Institute, with dditional support, and the anastrozole and fulvestrant for the trial, provided by AstraZeneca Pharmaceuticals LP. Source: EurekAlert! 12/7/11

Plant Extract Found to Improve Memory and Test Scores in College Students

Pycnogenol®, a natural supplement antioxidant plant extract from the bark of the French maritime pine tree, was found to significantly enhance mental performance in healthy college students in a recent clinical trial published in Panminerva Medica. The study was conducted at Pescara University and examined 53 Italian university students, ages 18 to 27. Students were assigned to a control or test group. The test group was given 100 mg of Pycnogenol per day over a period of eight weeks. Students' mental performance was evaluated using cognitive function tests that were carried out by computer-assisted methods. Students' final exam scores were also evaluated. Verbal IQ tests ensured that students recruited for the study demonstrated highly comparable intelligence. The study found that Pycnogenol effectively enhanced mental performance, including improved sustained attention, memory, and mood; students taking Pycnogenol had higher test scores on university exams than the control group; and alertness and contentedness improved significantly within the Pycnogenol group, and levels of anxiety decreased by 17 percent. Researchers suggest that several physiologic contributions of Pycnogenol may have contributed to the improved cognitive function of investigated students, namely antioxidant potency and blood circulation improvement. While the results are promising, they need to be further investigated in a larger population group. The extract has been widely studied for the past 40 years and has more than 280 published studies and review articles ensuring safety and efficacy as an ingredient. Source: PRNewswire 12/7/11

First Patient Enrolled in Phase IIb Study for Treatment of Graft-Versus-Host Disease

Therakos, Inc. in December announced that the first patient has been enrolled in its Phase IIb clinical study evaluating the use of the company's photopheresis technology in the treatment of patients with moderate-to-severe chronic graft-versus-host disease (GvHD), a life-threatening condition occurring when a donor's transplanted stem cells attack the recipient's body. The study will assess the safety and efficacy of extracorporeal photopheresis (ECP) treatment as an add-on to the standard of care for this condition. ECP is a therapeutic procedure performed outside the body using either the company's Uvar™ XTS™ or the Cellex™ photopheresis system to withdraw a volume of whole blood that is then centrifuged to separate the white blood cells from the red blood cells and plasma. The red blood cells and plasma are immediately returned to the patient. The white blood cells are treated with methoxsalen, which is photoactivated after exposure to UVA light. The treated white blood cells are then reinfused into the patient.. Patients will be enrolled over an 18-month period. Randomization will occur in a 1:1 ratio, with half of the patients receiving the current standard of care and the other half receiving standard of care coupled with ECP. The clinical study will consist of patients from across the United States and Europe. There will be roughly 35 sites participating in the clinical trial. Full results of the study are expected in early 2013, and will form the basis for a global Phase III study. Source: PRNewswire 12/6/11

Two-Year Results of Phase III Wet AMD Studies Show Sustained Improvement in Visual Acuity

Regeneron Pharmaceuticals, Inc. and Bayer HealthCare in December announced that in an integrated analysis of two parallel Phase III studies (VIEW 1 and VIEW 2) in patients with the neovascular form of age-related macular degeneration (wet AMD), patients treated with Eylea™ (aflibercept) intravitreal injection showed a sustained improvement in visual acuity at 96 weeks versus baseline. The 52-week results (primary analyses) from these studies have previously been reported. During the first year of the VIEW 1 and VIEW 2 studies, patients were treated with three different dosing regimens of Eylea (0.5 mg every four weeks, 2 mg every four weeks, and 2 mg every eight weeks [following three initial monthly injections]), compared to ranibizumab 0.5 mg every four weeks. The Eylea 2 mg every eight week regimen was recently approved by the U.S. Food and Drug Administration, based on efficacy (maintenance of vision) that was clinically equivalent at one year to the monthly ranibizumab regimen. In the second year of the studies, patients were treated with the same dose per injection as in the first year, and were evaluated monthly to determine need for retreatment. Patients were treated at least every 12 weeks. All year two analyses were considered exploratory. In an integrated analysis of the VIEW 1 and VIEW 2 studies, the visual acuity gain from baseline in the Eylea 2 mg every eight week group at week 96 was 7.6 letters compared to 8.4 letters at week 52, with an average of 11.2 injections over two years and 4.2 injections during the second year. The visual acuity gain from baseline in the monthly ranibizumab group at week 96 was 7.9 letters compared to 8.7 letters at week 52, with an average of 16.5 injections over two years and 4.7 injections during the second year. The results of each of the VIEW 1 and VIEW 2 studies were consistent with the integrated analysis. The proportion of patients who required frequent injections (six or more) during the second year was lower in the Eylea 2 mg every eight week group compared to the ranibizumab group (15.9 percent versus 26.5 percent). Further results from year two of the studies will be presented at upcoming medical conferences. The VIEW (VEGF Trap: Investigation of Efficacy and Safety in Wet AMD) program consists of two randomized, double-masked, Phase III clinical trials evaluating Eylea in the treatment of wet AMD. The VIEW 1 study, which randomized 1,217 patients, was conducted in the United States and Canada by Regeneron. The VIEW 2 study, which randomized 1,240 patients, was conducted in Europe, Asia Pacific, Japan, and Latin America by Bayer HealthCare. The study designs are essentially identical. The primary endpoint evaluation was conducted at 52 weeks. Source: PRNewswire 12/5/11

Phase II Trial in Pancreatic Cancer Reaches Primary Endpoint

Oncolytics Biotech Inc. in December announced that interim data from a Phase II clinical trial using intravenous administration of Reolysin® in combination with gemcitabine (Gemzar®) in patients with advanced pancreatic cancer (REO 017) indicated that the clinical study had successfully reached its primary endpoint, and that the drug combination is active. To date, eight of 13 evaluable patients in the study had stable disease for 12 weeks or longer, for a clinical benefit rate of 62 percent. The study is using a one sample, two-stage design. In the first stage, 17 patients were to be enrolled, and best response noted. If three or more responses were observed among the 17 patents, the study would enroll an additional 16 patients for a total of 33 evaluable patients. As previously disclosed, this initial endpoint was met after six evaluable patients were enrolled. If at least eight responses were observed out of 33 patients, the study would have reached its primary endpoint and concluded that the drug combination is active; this was achieved with just more than a third of enrollment completed. The company will continue to enroll in this study to evaluate the progression-free survival of the patient group, and will continue testing Reolysin with various chemotherapeutic agents, including gemcitabine and carboplatin/paclitaxel across multiple trials to further understand its potential in the treatment of pancreatic cancer. Source: PRNewswire 12/2/11

Vaccine Targeting Latent TB Enters Clinical Testing

Statens Serum Institut and Aeras in late November announced the initiation of the first Phase I clinical trial of a new candidate tuberculosis (TB) vaccine designed to protect people latently infected with TB from developing active TB disease. The trial is being conducted by the South African Tuberculosis Vaccine Initiative at its field site in Worcester, in the Western Cape province of South Africa. Dr. Hassan Mahomed is the principal investigator. The candidate TB vaccine (SSI H56-IC31) is a subunit vaccine containing recombinant TB proteins formulated in a proprietary adjuvant IC31® from Intercell. It is being developed under a consortium of researchers led by Peter Andersen at the Statens Serum Institut, based in Copenhagen. The consortium is supported as part of the Grand Challenges in Global Health, an initiative that fosters scientific breakthroughs needed to prevent, treat, and cure diseases of the developing world. This clinical trial will be the first to test this vaccine candidate in people. It will assess the safety and immunogenicity of SSI H56-IC31 in 25 adults, including participants with and without latent TB infection. SSI H56-IC31 has been tested in several preclinical studies with no safety concerns, and has shown efficacy in small animal models administered both before infection and to latently infected animals. The vaccine was also shown to control clinical disease and reactivation in a nonhuman primate model. This is the first time a South African research institute has led a first-in-human Phase I clinical trial of a new TB vaccine. SSI H56-IC31 is being developed for both adolescent and adult populations. The trial has been approved by the Medicines Control Council of South Africa. Preliminary results of this trial are expected at the end of 2012. Source: EurekAlert! 12/1/11

Positive Results Seen in Phase II ALS Study

Cytokinetics, Inc. in November announced positive results from the first cohort, or Part A, of a continuing double-blind, randomized, placebo-controlled Phase II clinical trial of CK-2017357 in patients with amyotrophic lateral sclerosis (ALS). CK-2017357 selectively activates the fast skeletal muscle troponin complex by increasing its sensitivity to calcium, which increases skeletal muscle force in response to neuronal input and delays the onset and reduces the degree of muscle fatigue. CK-2017357 is the lead drug candidate from the company's skeletal muscle contractility program. The objective of Part A of the trial was to evaluate the tolerability of a range of doses of CK-2017357 in ALS patients not currently taking riluzole. The drug successfully achieved its primary objective in demonstrating that CK-2017357 was well-tolerated as a single agent when dosed in these patients at all dose levels from 125 mg daily to 375 mg daily for two weeks. The most common and dose-related side effect reported was dizziness, observed in no patients receiving placebo and eight of the 18 patients receiving CK-2017357. The dizziness did not persist beyond the second day of dosing in all but one of the patients studied. Two patients withdrew early, both due to treatment-emergent dizziness. No serious adverse events were reported. Part A of this trial lacked the statistical power to detect significant differences in clinical outcome measures. However, trends toward improved clinical outcome measures were observed, especially at the highest CK-2017357 dose of 375 mg daily. Four of five patients who completed treatment in this dose group reported improvement in their Global Assessments and three of these five patients improved at least 1 point on the ALS Functional Rating Scale-Revised. Additional analyses from this ongoing clinical trial, including results from efficacy outcome measures, are expected to be presented at a later date. Source: Marketwire 11/30/11

NIH Modifies HIV Prevention Study

A large-scale clinical trial evaluating whether daily use of an antiretroviral-containing oral tablet or vaginal gel can prevent HIV infection in women is being modified because an interim review found that the gel, an investigational microbicide, was not effective among study participants. On November 17, an independent data and safety monitoring board (DSMB) recommended that the Vaginal and Oral Interventions to Control the Epidemic (VOICE) study evaluating daily use of 1 percent tenofovir vaginal gel be discontinued because there was no difference in effect demonstrated between the drug-containing gel and a placebo gel. The DSMB found a 6 percent HIV incidence rate among participants in the tenofovir gel group and the placebo gel group. The study is being conducted by the National Institutes of Health (NIH)-funded Microbicide Trials Network (MTN). As the trial's primary sponsor, the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, concurred with the DSMB's recommendation and has requested that the MTN discontinue use of tenofovir gel (and placebo gel) in the VOICE study. Because the trial is continuing, all other study data remain confidential, so NIAID cannot speculate about why tenofovir gel showed no benefit among VOICE study participants. Factors that may have contributed to this outcome are being further investigated. Importantly, the DSMB found no major safety concerns with either the tenofovir gel or oral tablets containing tenofovir and emtricitabine given to women in a different arm of the study. Oral tenofovir and emtricitabine, a combination drug called Truvada that currently is used to treat HIV infection, will continue to be investigated in the VOICE study to determine whether it can prevent HIV infection in women in this trial. The VOICE study, or MTN-003, began in September 2009 and originally enrolled more than 5,000 HIV-uninfected women in South Africa, Uganda, and Zimbabwe. The study was first modified in September 2011, following the DSMB recommendation to discontinue evaluating oral tenofovir-only tablets, based on interim data demonstrating that the study would be unable to show a difference in effect between tenofovir tablets and placebo tablets in preventing HIV infection. No safety concerns with oral tenofovir were found. Since that time, the study participants who were taking oral tenofovir have been informed of the discontinuation of this arm of the trial, and currently they are undergoing their final study-associated tests and procedures. Based on its November 17 scheduled review, the DSMB recommended that the roughly 2,000 women in the tenofovir gel and placebo gel groups stop applying the study product. The study team will immediately begin informing all VOICE participants of this new development and will soon start the orderly discontinuation of the two gel arms of the trial. Follow-up for all of the VOICE study participants is expected to be completed in June 2012, with final study results anticipated in early 2013. The trial will continue to examine the question of whether oral Truvada is a safe and effective HIV prevention measure for women in this study. Source: EurekAlert! 11/27/11

First Patient Dosed in Cervical Region in ALS Stem Cell Trial

Neuralstem, Inc. has announced that the first patient to receive stem cells in the cervical (upper back) region of the spine was treated November 18 in its ongoing trial to test the safety of its spinal cord neural stem cells in amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) at Emory University. Patient 13 is the first in the trial to be dosed in this region. It is also the first time surgeons have gone into the gray matter of the cervical region. The initial 12 patients in the trial all received stem cell transplants in the lumbar (lower back) region of the spinal cord only. Details about the surgery and interviews with the doctors were highlighted in a story on CNN (11/22/11) and can be viewed here. The ultimate goal of transplanting cells into the cervical region is to preserve or even enhance breathing capacity for the patients. According to the company, successfully intervening in the cervical region entails enhanced risk, but also the possibility of dramatically enhanced benefit to the patients. The Phase I trial to assess the safety of Neuralstem's spinal cord neural stem cells and intraspinal transplantation method in ALS patients has been under way since January 2010, and is designed to enroll up to 18 patients, the final six of whom will be treated in the cervical region. The entire 18-patient trial concludes six months after the final surgery. Source: PRNewswire 11/23/11

Drug for Type 1 Diabetes Meets Primary and Secondary Goals in Phase III

Andromeda Biotech in November announced results for its Type 1 diabetes drug, DiaPep277®, in a randomized, regulated, double-blinded, broad-based Phase III trial in 457 patients, aged 16 to 45, diagnosed with type 1 diabetes, in nearly 40 centers in Europe, Israel, and South Africa. The patients in the trial were randomly assigned to one of two groups: One received DiaPep277 through a subcutaneous injection once every three months, for a period of two years, while the control group was given a placebo in the same way. In addition, all of the patients received insulin as needed to stabilize their glucose levels. DiaPep277 was invented by Prof. Irun Cohen and his team at the Weizmann Institute of Science. It is a peptide containing 24 amino acids, and is derived from the sequence of the human heat shock protein 60 (Hsp60). The peptide acts by modulating the immune system, preventing the destruction of the pancreatic cells that secrete insulin and preserving their natural function. Treatment of type 1 diabetes patients with DiaPep277 is intended to slow the deterioration of the diseased tissue, improve metabolic control, reduce daily insulin requirements, and lessen the complications of diabetes. During the trial, the ability of the patients' pancreas to secrete insulin was tested. From an initial analysis of the results, it appears that the patients treated with the drug for a year or more had significantly higher pancreas function than those in the control group. From the point of view of safety, no significant differences were found in the incidence of side effects between the treated and control groups. Additional data on the drug's efficacy and safety were collected and evaluated, and these will be presented in a final report on the trial, which will be completed in several months. Andromeda Biotech is now planning to conduct another trial, to try to reproduce these results. Recruitment of patients into this trial is expected to be finalized in the second quarter of 2012. Cohen's research is supported by the Laszlo N. Tauber Family Foundation. Source: EurekAlert! 11/22/11

Company Provides Update on Phase III for Hypogonadism Treatment

Trimel Pharmaceuticals Corp. announced in November that 28 of the 30 trial sites involved in executing its U.S. Phase III CompleoTRT study for the treatment of male hypogonadism are actively recruiting patients. Cumulatively speaking, the clinical sites have screened more than 250 patients, 59 of which are proceeding through the remaining stages of the screening process. Fifteen of the estimated 280 patients required for the trial are receiving medication. The company is replacing the two nonactive sites with backup facilities, and thus expects to have all 30 sites operational within the coming weeks. CompleoTRT is designed to represent a significant advancement in the treatment of male hypogonadism, or low testosterone, through a delivery technology designed to provide patients with the therapeutic effect of supplementing testosterone levels with a small amount of drug in the form of a bioadhesive intranasal gel. CompleoTRT's intranasal no-touch delivery system is designed to avoid the risk of accidental transfer (secondary transference) of testosterone to spouses or other family members, thus offering patient benefits and improved safety as compared to other currently marketed products for the condition. Moreover, CompleoTRT is designed to avoid the negative effects from first-pass metabolism on the product, liver, or both. Trimel's research program to date has demonstrated that CompleoTRT is safe and effective, with more than 3,500 drug exposures studied thus far in the United States. Source: Marketwire 11/21/11

Phase II Study Completed for Lactose Intolerance Treatment

Ritter Pharmaceuticals, Inc. announced in November the last patient has completed treatment in its Phase II study for RP-G28, a first-in-class treatment for symptoms associated with lactose intolerance. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study evaluated the effectiveness, safety, and tolerability of RP-G28. The study aims to demonstrate a significant drug effect correlating microbial changes and patient reported symptom improvements. Novel microbiome sequencing and genetic analysis will identify the microbiota of lactose intolerant individuals and contribute to the understanding of changes in colonic microflora, specifically, the modification and colonization by bacteria which improve lactose fermentation in the colon. RP-G28 has the potential to become the first prescription drug approved for the treatment of lactose intolerance, a debilitating disorder with long-term consequences. Lactose intolerance affects more than 80 million people in the United States and more than 4 billion people worldwide. The company plans to share data from the study in the first quarter of 2012. Source: Marketwire 11/17/11

Positive Results Announced from Phase IIa COPD Study

Theravance, Inc. announced in November positive topline results from a Phase IIa randomized, double-blind, four-period crossover, single-dose study of TD-4208, an investigational inhaled long-acting muscarinic antagonist (LAMA), discovered using Theravance's multivalent approach to drug design. This compound is under development by Theravance for the treatment of chronic obstructive pulmonary disease (COPD). In this study, TD-4208 met the primary endpoint by demonstrating a statistically significant mean change from baseline in peak forced expiratory volume in one second (FEV1) compared to placebo, and was generally well tolerated. In the study, two doses of TD-4208 (350 mcg and 700 mcg) and one of the active control ipratropium bromide (500 mcg, the marketed dose), administered via nebulizer, demonstrated statistically significant improvements in peak FEV1 versus placebo of 174 mL, 169 mL, and 176 mL, respectively. All three treatments demonstrated a rapid and similar onset of action. In a secondary analysis, both doses of TD-4208 demonstrated a long duration of action with statistically significant effect at 24 hours. The mean changes from baseline in FEV1 compared to placebo at 24 hours were 103 mL and 137 mL for 350 mcg and 700 mcg of TD-4208, respectively. As expected, ipratropium bromide did not produce significant effects versus placebo at 12 hours and 24 hours. The full results of the study will be presented at an upcoming medical conference. A total of 32 patients outside the United States, 40 to 75 years of age and with moderate to severe COPD, were randomized such that all patients received each of the four treatments. Source: Marketwire 11/14/11

Benefit of Novel Drug in Breast Cancer Seen in Blood Within Weeks

Clinical benefit from use of a novel histone deacetylase inhibitor drug may be determined by examining blood cells days after a patient receives treatment. The drug, entinostat, is the first histone deacetylase inhibitor successfully tested in a randomized, placebo-controlled study in metastatic breast cancer--and is the first to show that clinical outcome can be predicted shortly after administration. The findings, reported in November at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, represent an advance in the goal to offer patients only those therapies that will help treat cancer effectively, the researchers said. "The ability to have a marker of benefit within the first several weeks of using this drug represents an exciting advance in personalized medicine," said lead researcher Peter Ordentlich, PhD, executive director of translational science and a founder of Syndax Pharmaceuticals Inc., which developed entinostat, an oral small-molecule drug that inhibits enzymes that alter the packaging of DNA inside the nucleus, which controls gene expression. "The goal of entinostat in breast cancer is to extend the benefit of hormone therapy and delay the time that patients will need to use chemotherapy," said Ordentlich. To test that strategy in ER-positive metastatic breast cancer, Syndax Pharmaceuticals conducted ENCORE-301, a randomized, placebo-controlled, Phase II study (n = 130) testing the use of exemestane, an aromatase inhibitor, with either entinostat or placebo. Results of the clinical trial, released in September, showed that the combination therapy delayed cancer progression by 27 percent (4.3 versus 2.3 months) compared to exemestane treatment alone. At a median follow-up of 18 months, overall survival was also significantly longer with exemestane plus entinostat than with exemestane plus placebo (26.9 versus 20.3 months). In this subset analysis, researchers examined blood samples from 49 patients (27 received combination therapy) to evaluate whether changes in circulating blood cells that reflected the activity of the histone deacetylase inhibitor could be detected. Researchers measured protein lysine acetylation, a biological marker of entinostat activity, in B cells, T cells, and monocytes in blood samples taken at pretreatment and one, eight, and 15 days after therapy with entinostat, which is taken once a week. While levels of lysine acetylation after one day were not linked to clinical benefit, levels measured eight and 15 days after therapy were related to clinical benefit, Ordentlich said. Researchers found that patients with elevated levels of protein lysine acetylation had a 68 percent reduced risk for disease progression compared to those patients who did not have sustained elevated levels. Researchers found that hyperacetylation was also associated with longer median progression-free survival across cell lines: B cells, 8.5 versus 1.9 months; T cells, 6.6 versus 1.8 months; and monocytes, 6.2 versus 1.9 months. Source: EurekAlert! 11/13/11

Researchers Reaffirm Drug's Utility in High-Risk PCI Patients

The ISAR group, world leading cardiology researchers based in Munich, Germany, in November simultaneously presented and published results of the 1,721-patient, randomized, double-blind, active-controlled, multicenter ISAR-REACT-4 clinical trial in patients with evidence of evolving infarction (heart attack) undergoing percutaneous coronary interventions (PCI). The Medicines Company announced that the late-breaking results were presented at the American Heart Association Scientific Sessions 2011 and published in The New England Journal of Medicine. The study's purpose was to determine whether the combination of unfractionated heparin and abciximab (ReoPro®) is more effective than bivalirudin (Angiox® in Europe, Angiomax® in the United States) in preventing thrombotic and bleeding complications in patients suffering from a heart attack known as non-ST segment elevation myocardial infarctions (NSTEMI) and undergoing PCI. ISAR-REACT-4 tested how many patients in each treatment group within 30 days of treatment died, had another major heart attack, required another procedure to unblock the same artery, or suffered major bleeding. The study team found: 95 patients (11 percent) taking bivalirudin had at least one of those outcomes compared to 94 (10.9 percent) of those taking abciximab and heparin; and 22 patients (2.6 percent) on bivalirudin experienced major bleeding compared to 40 patients (4.7 percent) taking abciximab and heparin. Source: Marketwire 11/13/11

Two Phase IIa Studies Initiated for Airway Inflammation

Aquinox Pharmaceuticals Inc. announced in November that it has initiated two Phase IIa clinical studies to measure AQX-1125's ability to prevent inflammation. The studies, both scheduled for completion during 2012, are being conducted at centers of excellence in the United Kingdom. The first study will evaluate a single dose of AQX-1125 in a randomized, double-blind, placebo-controlled trial in mild and moderate asthmatic patients exposed to an allergen known to induce an asthmatic attack. In the second study, AQX-1125 will be given in a randomized, double-blind, placebo-controlled fashion at one of two doses to volunteers exposed to an environmental inflammatory stimulus. In each study, subjects will be administered the drug orally once daily for seven days with a key endpoint being AQX-1125's ability to reduce inflammatory cells and markers in sputum (indicators of the drug's anti-inflammatory properties). The studies will also continue to evaluate AQX-1125's safety and residence time in the blood (pharmacokinetics). Earlier in the year, Aquinox successfully completed a Phase I clinical study assessing the safety, tolerability, absorption, and pharmacokinetics of AQX-1125. In this study, AQX-1125 was rapidly absorbed and exhibited a dose-proportional pharmacokinetic profile over the range of doses tested with a half-life of approximately 22 hours. Source: Marketwire 11/10/11

Phase Ib Study for Treatment of Type 2 Diabetes Yields Positive Results

DARA BioSciences, Inc. announced in early November the positive results from a successfully completed Phase Ib clinical study for DB959, its peroxisome proliferator activated receptor (PPAR)-delta/gamma agonist, a non-TZD oral drug in development for the treatment of type 2 diabetes. This study’s main objectives were to determine the safety and pharmacokinetics of multiple ascending oral doses of DB959Na. Overall, the safety profile of once-daily doses of DB959Na for seven sequential days was comparable to placebo, demonstrating that DB959Na is safe and well-tolerated throughout the 40-fold dose range tested. Results of steady-state pharmacokinetic measurements indicate that the compound is highly likely to meet the target dosing regimen of once-a-day. Changes in the circulating profile of adiponectin, the established biomarker of PPAR agonism, seen in this study suggests that DB959Na will be pharmacologically active in patients with type 2 diabetes within the well-tolerated dose range utilized in this study. The study was a randomized, placebo-controlled, double-blind, escalating multiple-dose clinical trial that enrolled 32 healthy male and female volunteers at Quintiles’ Phase I facility in Overland Park, Kansas. The company plans to present detailed results at an upcoming scientific meeting in the first half of 2012. These positive results will allow DB959 to enter Phase II; DARA has begun planning for a Phase IIa study in patients with type 2 diabetes. DB959 activates certain nuclear receptors (PPARs) that regulate the genes involved in controlling blood sugar levels and certain lipids (e.g., total cholesterol, HDL-cholesterol, triglycerides). The compound acts as an agonist of PPAR-delta and PPAR-gamma. Source: Newswise 11/1/11

First Patient Enrolled in LVAD Study

Thoratec Corp. in early November announced the enrollment of the first patient into the ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device [LVAD] and Medical Management in Ambulatory Heart Failure Patients) study. The patient was enrolled at INTEGRIS Baptist Medical Center in Oklahoma City, Okla. ROADMAP is a postmarket study of the HeartMate II® Left Ventricular Assist System as a "destination therapy" device. The study will involve ambulatory advanced heart failure patients who are not yet dependent on intravenous inotropic support and are typically categorized as INTERMACS profiles 4-6, within the existing Food and Drug Administration-approved indication for destination therapy. The primary objective of the prospective, multicenter, nonrandomized, controlled, observational study is to evaluate and compare the effectiveness of HeartMate II support versus optimal medical management (OMM). Subjects will be enrolled in one of two cohorts: OMM or LVAD. Clinical investigators and the patients will decide which cohort a patient will enter based on the center's standard of care and patient acceptance of therapy options. Baseline risk assessment profiles will allow for stratification of expected risk and severity of illness. The study will include 200 patients at up to 50 sites, including experienced HeartMate II implant centers as well as community centers that care for a large volume of advanced heart failure patients. Patients will be followed for two years, and the primary endpoint will be a composite of survival and functional improvement, as measured by the six-minute walk test, at one year. Secondary endpoints include actuarial survival, quality of life, pump replacement, adverse events, and rehospitalizations. Source: PRNewswire 11/3/11

Data from First-in-Human Stent Study Presented

Micell Technologies, Inc. in early November announced that it has completed a preliminary analysis of data from the first-in-human clinical study, DESSOLVE I, of the MiStent® Sirolimus Drug Eluting Coronary Stent System (DES), a thin, drug-eluting stent distinguished by a rapid-absorbing drug/polymer coating formulation that is designed for controlled drug release. Four-, six-, and eight-month data were presented at the Transcatheter Cardiovascular Therapeutics Conference in San Francisco, Calif., on November 8, by John Ormiston, MD, interventional cardiologist with the Auckland Heart Group and medical director at Mercy Angiography in Auckland, New Zealand. William Wijns, MD, interventional cardiologist with the Cardiovascular Center, Aalst, Belgium, and John Ormiston, MD, are principal investigators for the study. In the DESSOLVE I clinical trial, the MiStent DES was used to treat 30 patients with de novo lesions in coronary arteries ranging in diameter from 2.5 to 3.5 mm and amenable to treatment with a maximum 23 mm length stent. The study was performed in five centers in New Zealand, Australia, and Belgium. This trial focused on evaluating the efficacy of the MiStent DES, and examined three independent groups of 10 patients using angiography, intravascular ultrasound, and optical coherence tomography (OCT) at four, six, and eight months to evaluate the rate of in-stent late lumen loss and the extent of tissue coverage of the stent at each time point. Micell Technologies currently is conducting a second trial of the MiStent DES, DESSOLVE II; a prospective, single-blind, unbalanced randomized, controlled, multicenter superiority trial in Europe, Australia, and New Zealand. This trial completed enrollment in July 2011 with 183 patients enrolled. The MiStent DES is an investigational device, and is not yet approved or available for sale in any market. Source: PRNewswire 11/2/11

New Therapy Marks a Milestone in Fight Against Cystic Fibrosis

Results of the pivotal Phase III clinical trial published in the November 3 New England Journal of Medicine show that the oral medication ivacaftor (VX-770) provides major, sustained improvement in lung function, growth, and other signs and symptoms for cystic fibrosis (CF) patients. The multisite study marks the first time a drug has been shown to work on the disease process rather than on the symptoms. CF, which has no cure, is the most common lethal genetic disease in Caucasians. Ivacaftor, a drug developed by Vertex Pharmaceuticals, targets the underlying cause of CF, with the goal of preventing or slowing the development of related complications. Ivacaftor is a "potentiator" of the mutant CF transmembrane conductance regulator (CFTR) protein--the fundamental defect in cystic fibrosis – and acts by restoring the balance of salt and water on the surface of the airways. University Hospitals Case Medical Center received funding from Vertex Pharmaceuticals for the research. Additional support for conducting these and other CF-related studies comes from Case Western Reserve University School of Medicine and Cystic Fibrosis Foundation Therapeutics. The pivotal Phase III clinical trial, conducted in 161 people with CF ages 12 years and older with a specific CF mutation known as G551D (affecting 4 percent of people with CF), showed that taking the oral medication twice daily for 48 weeks improved several key outcome measures of CF, including lung function, growth, and sweat chloride levels. Two key questions remain: The first is whether VX-770 can halt deterioration of lung function, which is not clear from this study; the second is if the medication can have an effect on other CFTR defects and possibly benefit more than the 4 percent of patients affected by the G551D mutation. More than 90 percent of CF patients are affected by another mutation called 508-CFTR. Source: EurekAlert! 11/2/11

Interferon-Free Phase III Program Under Way for HCV Treatment

Pharmasset, Inc. in early November announced the initiation of a Phase III program with the hepatitis C virus (HCV) nucleotide analog, PSI-7977. This pivotal program will evaluate a 12-week, all-oral, interferon-free regimen of PSI-7977 and ribavirin in patients with HCV, independent of viral genotype or their ability to take interferon therapy. The first trial, FISSION, will enroll approximately 500 treatment-naive patients with HCV genotype 2 or 3, and will evaluate the safety and efficacy of a 12-week interferon-free regimen of PSI-7977 and ribavirin compared to 24 weeks of pegylated interferon and ribavirin. The primary endpoint of the study is sustained virologic response 12 weeks after the completion of treatment. Pharmasset plans to initiate a second 12-week duration, interferon-free Phase III trial, POSITRON, in early 2012. This trial will enroll approximately 225 patients with HCV genotype 2 or 3 who cannot take interferon. In mid-2012, Pharmasset intends to initiate a third 12-week duration, interferon-free Phase III trial, NEUTRINO. This trial will enroll approximately 280 patients who cannot take interferon, and will include patients with HCV regardless of viral genotype, including those with HCV genotype 1. The final study design will be based on emerging data from the ongoing ELECTRON study and from PSI-7977 plus ribavirin-containing arms in the ongoing QUANTUM study. FISSION, POSITRON, and NEUTRINO are all expected to be conducted at more than 100 centers in the U.S., Europe, and other territories. Pharmasset anticipates submitting data from all three Phase III trials in the second half of 2013 to support the marketing approval of PSI-7977 in the U.S. and European Union. Source: PRNewswire 11/1/11

Trial Begins for the Alleviation of Chronic Low Back Pain

Relievant MedSystems Inc. in late October announced the company has enrolled the first patient in its SMART trial to evaluate the Intracept® Basivertebral Nerve Ablation Procedure. The Surgical Multicenter Assessment of RF Ablation for the Treatment of Vertebrogenic Back Pain (SMART) trial is a Level 1, prospective, randomized, double-blind, sham-controlled clinical trial evaluating the reduction of pain in patients with chronic axial low back pain. The landmark SMART trial is enrolling 200 patients in up to 20 leading medical centers across the U.S. to determine the safety and effectiveness of the Intracept procedure. The primary endpoint is the evaluation of patient improvement in Oswestry Disability Index (ODI) at three months compared to baseline between treatment and sham populations. In addition, change in multiple patient-reported outcomes from baseline will be assessed at three, six, and 12 months as well as safety evaluations at all time points. Importantly, patients and clinicians who perform the follow-up evaluations are blinded to the randomization of the sham versus experimental procedure. Relievant is also initiating a separate and similar Level 1 study in Europe. Enrollment for both studies is expected to be completed in early 2013. Source: PRNewswire 10/31/11

First Patient Enters Phase II Allergy Study

HAL Allergy B.V. in late October announced that it has included the first patient in its PHASE II dose range-finding study. This multicenter, randomized, double-blind, placebo-controlled study in patients with persistent allergic rhinitis/rhinoconjunctivitis will characterize the dose-response relationship of PURETHAL Mites in order to support the optimal dose in terms of clinical efficacy and safety. The study has been initiated in September 2011 in five European countries. PURETHAL Mites is currently on the market in Germany and several other European countries on a named patient basis. Due to changes in the regulatory landscape, immunotherapy products containing common allergens (such as house dust mite) can remain on the market, but require a development program that is designed to obtain full marketing authorization. The approval and start of this study are important steps to obtain final licensure for the use of PURETHAL Mites in the treatment of immediate type allergic disorders (IgE-mediated), such as allergic rhinitis and allergic conjunctivitis induced by house dust mite allergy. It follows the submission of a marketing authorization application (November 2010) for PURETHAL Mites at the Paul-Ehrlich-Institute, the regulatory authority in Germany. The design of the study complies with the current state-of-the-art guidelines on the clinical development of products for specific immunotherapy for the treatment of allergic diseases and the German Regulation on Therapy Allergens. PURETHAL Mites is a modified aluminum hydroxide-adsorbed extract of house dust mites for subcutaneous use. The product is in commercial use and is primarily prescribed for patients suffering from severe allergic respiratory diseases inadequately controlled despite the use of symptomatic treatments. Source: PRNewswire 10/31/11

Phase III Trial Launched for Menopausal Hot Flashes

Bionovo, Inc. in October announced that enrollment has started for a Phase III pivotal clinical trial evaluating the safety and efficacy of two doses of Menerba™ (MF101) among a cohort of postmenopausal women for the treatment of menopausal hot flashes. The multicenter, double-blind, placebo-controlled, randomized trial will involve a total of 50 clinical sites in the U.S. and 1,200 postmenopausal women between the ages of 40 and 65 years. Participants will be randomized to Menerba 5 g/day, Menerba 10 g/day, or placebo, with the primary aims of the study being to determine the safety and efficacy of the two doses compared to placebo after 12 weeks of treatment. Efficacy will be measured by the reduction of moderate to severe hot flushes from baseline to 12 weeks of treatment. The new trial is one of two Phase III trials required by the Food and Drug Administration for approval of the product, which is an estrogen receptor beta selective drug manufactured from botanical sources. The company expects to have top-line data from this study in approximately 18 months. Menerba also has been shown in animal studies to prevent the proliferation of breast cancer and to have a beneficial effect on osteoporosis, but this has not yet been studied in humans. Source: PRNewswire 10/26/11

New Drug May Revolutionize Treatment of Atrial Fibrillation

New research has the potential to revolutionize the treatment of atrial fibrillation (AF), a common type of heart arrhythmia that puts those affected at a three to five times greater risk for stroke. Now, there is a new drug poised to battle the condition. "The majority of patients with [AF] need an anticoagulant. The current anticoagulant can be a burden for physicians and patients due to its side effects and narrow therapeutic range," Dr. Justin Ezekowitz, from the University of Alberta, told a late-breaking clinical trial session at the Canadian Cardiovascular Congress 2011. "It is associated with a risk of bleeding and needs very close monitoring, whereas this new drug is taken twice a day and does not require monitoring. Our trial also shows it is not just equivalent, but better than warfarin for preventing strokes. These are important advantages." In a recent double-blind, double-dummy trial, as compared to dose-adjsted warfarin, 5 mg twice daily of apixaban, a new type of oral anticoagulant known as a factor Xa inhibitor, resulted in fewer strokes (ischemic or hemorrhagic) and fewer systemic embolisms, caused less bleeding, and resulted in fewer deaths in patients with AF. It is the largest prospective trial yet reported for stroke prevention in AF, and randomized 18,201 patients with at least one additional risk factor for stroke, such as age greater than 75 years, prior stroke or transient ischemic attack, systemic embolism, heart failure or left ventricular ejection fraction less than 40 percent, diabetes, or high blood pressure. The patients came from more than 1,000 sites in 39 countries, and were followed for 1.8 years, on average. Apixaban reduced the chance of stroke and systemic embolism by 21 percent, reduced major bleeding by 31 percent, and reduced mortality, or all-cause death, by 11 percent. Source: EurekAlert! 10/26/11

Septic Shock Drug Withdrawn Following Recent Clinical Trial Results

Eli Lilly and Co. in late October announced withdrawal of its Xigris® [drotrecogin alfa (activated)] product in all markets following results of the PROWESS-SHOCK study, which showed the study did not meet the primary endpoint of a statistically significant reduction in 28-day all-cause mortality in patients with septic shock. The company is working with regulatory agencies on this withdrawal, and is in the process of notifying healthcare professionals and clinical trial investigators. "While there were no new safety findings, the study failed to demonstrate that Xigris improved patient survival and thus calls into question the benefit-risk profile of Xigris and its continued use," said Timothy Garnett, MD, Lilly's senior vice president and chief medical officer. "Patients currently receiving treatment with Xigris should have treatment discontinued, and Xigris treatment should not be initiated for new patients. We believe the original Xigris approval was appropriate and these recent results were quite unexpected. A contributing factor to these study results could be advances in the standard of care for treating severe sepsis over the past 10 years." Xigris was approved in the United States by the Food and Drug Administration in November 2001, and was licensed in the European Union in 2002. The PROWESS-SHOCK study was initiated in March of 2008 as a condition for continued market authorization in Europe. Lilly committed to conduct a new placebo-controlled clinical trial to help refine appropriate patient identification for treatment with Xigris and to confirm the benefit-risk profile of the product. Source: PRNewswire 10/25/11

Third Clinical Safety Study of New Anthrax Treatment Initiated

Elusys Therapeutics, Inc. announced in October that it is initiating a new clinical study to further demonstrate the safety of Anthim (ETI-204), the company's antitoxin in late-stage development for prevention of disease and death from exposure to inhaled anthrax. The company also announced it has successfully manufactured Anthim at commercial scale. Anthim significantly increases survival in anthrax-infected animals and is a promising candidate for the treatment of anthrax infection in people following a biowarfare attack. The double blind, placebo-controlled, dose-escalating study will include a total of 108 healthy human subjects and is designed to collect additional safety and pharmacokinetic data on Anthim. Anthrax is a life-threatening infectious disease caused by the bacterium Bacillus anthracis, and remains one of the nation's top biowarfare threats. Inhaled anthrax is usually fatal, despite treatment with antibiotics, unless the patient is treated soon after exposure. If all activities in the Anthim development program are completed to the U.S. Food and Drug Administration's satisfaction, the federal government could purchase Anthim for the Strategic National Stockpile under Project BioShield. Project BioShield was established in 2004 to provide much-needed funding to procure important countermeasures to protect the American public in the event of a biowarfare attack. Anthim is a high-affinity, humanized, and deimmunized monoclonal antibody that targets the protective antigen of B. anthracis and neutralizes the lethal effects of anthrax toxins. Anthim has been extensively tested for efficacy and safety in animals and safety in human volunteers. Source: PRNewswire 10/24/11

Additional Efficacy Data Announced from Phase IIa Trial in Celiac Disease

Alvine Pharmaceuticals, Inc. in October announced additional efficacy data from its Phase IIa clinical trial of ALV003. Results showed that oral ALV003, administered in the context of a gluten free diet (GFD), diminished gluten-induced intestinal mucosal injury in well-controlled celiac disease patients. The study findings were presented in a late-breaking oral session at the 19th United European Gastroenterology Week in Stockholm. Although removal of dietary gluten is currently the only treatment option available, it is virtually impossible to completely avoid gluten, so up to 60 percent of adult celiac disease patients continue to experience symptoms and up to 80 percent continue to have persistent intestinal inflammation despite adhering to a strict GFD. In the double-blind, placebo-controlled trial, 41 well-controlled, well-characterized adult celiac disease patients who were maintained on a GFD for one or more years were randomized to receive ALV003 or placebo daily for six weeks at the time of ingestion of 2 grams of gluten in the form of bread crumbs. Study participants underwent small bowel biopsy at the beginning of the trial and after being given the daily gluten challenge for six weeks. The primary endpoint was intestinal mucosal morphometry measured at baseline and at six weeks. Secondary endpoints included intraepithelial lymphocyte density, gastrointestinal symptoms as measured by Gastrointestinal Symptom Rating Scale scores, celiac serologies, safety, and tolerability. The data from this study show that targeting degradation of immunogenic gluten peptides appears to be a viable approach for the development of a nondietary therapeutic for celiac disease. Based on the results, the company believes that clinical proof-of-principle has been achieved, and is targeting 2012 to begin a Phase IIb trial of ALV003 as an adjunct to a GFD in celiac disease patients. Source: Marketwire 10/24/11

Enrollment Begins in U.S. Device Trial for Biomaterial

CryoLife, Inc. in October announced that it has enrolled the first patient in its U.S. Investigational Device Exemption (IDE) clinical trial for its BioFoam® Surgical Matrix protein hydrogel technology. In connection with the trial, BioFoam will be used as an adjunct to conservative measures of achieving hemostasis on newly resected liver parenchyma. The approved IDE is for a prospective, multicenter, randomized feasibility study evaluating safety outcomes of BioFoam as compared to a standard topical hemostatic agent. The feasibility investigation will be conducted at up to three investigational sites and will enroll 20 eligible subjects with 10 subjects in each treatment group. Upon successful completion of the feasibility study in the U.S., and subsequent Food and Drug Administration and Department of Defense approvals, a follow-on prospective, multicenter, randomized, controlled pivotal study is planned. It is currently anticipated that the pivotal investigation would enroll a total of 164 eligible subjects, 82 subjects in each treatment group across a maximum of 10 investigational sites. These data would then be used to support a U.S. Premarket Approval application to allow commercialization of BioFoam in the U.S. The primary objective of the pivotal investigation will be to demonstrate a decrease in the time to achieve intraoperative hemostasis (a complex process that causes bleeding to stop) following open liver resection surgery in subjects receiving an application of BioFoam compared to a control group (standard topical hemostatic agent). The secondary objectives of this investigation will be to compare time to hemostasis and the achievement of immediate hemostasis between the BioFoam group and control group to demonstrate that BioFoam is at least equivalent in performance. In Europe, CryoLife has completed a 55-patient, prospective, multicenter, single-arm study of BioFoam at three centers in the United Kingdom, Germany, and France. BioFoam, a protein hydrogel biomaterial, contains an expansion agent that generates a mixed-cell foam. The foam creates a mechanical barrier to decrease blood flow and pores for the blood to enter, leading to cellular aggregation and enhanced hemostasis. It is easily applied and can be used intraoperatively to control internal organ hemorrhage, limit blood loss, and reduce the need for future reoperations in liver resections. Source: PRNewswire 10/24/11

Phase II Trial to Evaluate Treatment for Advanced Bladder Cancer

OncoGenex Pharmaceuticals, Inc. announced in October that it has initiated patient enrollment in a randomized, Phase II clinical trial evaluating OGX-427, an inhibitor of heat shock protein 27 (Hsp27), in patients with advanced bladder cancer. The trial is designed to assess the potential survival benefit of combining OGX-427 with standard first-line chemotherapy, as well as its safety, tolerability, and optimal dosing regimen. Hsp27, which is overexpressed in many cancers, helps tumor cells survive by resisting the effects of anticancer treatments, such as chemotherapy and radiation therapy. OGX-427 has been evaluated in a Phase I trial in patients with breast, prostate, bladder, ovarian, and non-small cell lung cancer who previously failed potentially curative treatments, or for whom a curative treatment did not exist. Results of the Phase I trial, presented at the 2010 American Society of Clinical Oncology annual meeting, demonstrated anticancer activity, safety, and tolerability with OGX-427 as a single agent and in combination with chemotherapy. The international Phase II trial is a double-blind, placebo-controlled, three-arm, randomized trial that will enroll approximately 180 patients with advanced bladder cancer who have not previously received chemotherapy for metastatic disease and are not candidates for potentially curative surgery or radiotherapy. Patients will be randomized to receive gemcitabine, cisplatin, and OGX-427 at two dose-levels (600 mg and 1,000 mg) versus gemcitabine, cisplatin, and placebo. The study will be conducted at approximately 45 cancer centers throughout North America and Europe. In addition to this company-sponsored, advanced bladder cancer trial, OGX-427 is currently being studied in an investigator-sponsored Phase I trial of patients with superficial bladder cancer and an investigator-sponsored, randomized Phase II trial of men with castrate-resistant prostate cancer who have not received chemotherapy for metastatic disease. Preliminary data from these two trials are expected to be presented in early 2012. Source: PRNewswire 10/20/11

First Phase III Results Show Malaria Vaccine Candidate Reduces Risk

The first results from a large-scale Phase III trial of RTS,S, published online October 18 in the New England Journal of Medicine, show the malaria vaccine candidate provides young African children with significant protection against clinical and severe malaria with an acceptable safety and tolerability profile. The results were announced at the Malaria Forum hosted by the Bill & Melinda Gates Foundation in Seattle, Wash. The trial, conducted at 11 trial sites in seven countries across sub-Saharan Africa, showed that three doses of RTS,S reduced the risk of children experiencing clinical malaria and severe malaria by 56 percent and 47 percent, respectively. This analysis was performed on data from the first 6,000 children aged 5 to 17 months, over a 12-month period following vaccination. Clinical malaria results in high fevers and chills. It can rapidly develop into severe malaria, typified by serious effects on the blood, brain, or kidneys that can prove fatal. These first Phase III results are in line with those from previous Phase II studies. The widespread coverage of insecticide-treated bed nets (75 percent) in this study indicated that RTS,S can provide protection in addition to that already offered by existing malaria control interventions. The trial is ongoing, and efficacy and safety results in 6 to 12 week-old infants are expected by the end of 2012. These data will provide an understanding of the efficacy profile of the RTS,S malaria vaccine candidate in this age group, for both clinical and severe malaria. An analysis of severe malaria episodes so far reported in all 15,460 infants and children enrolled in the trial at 6 weeks to 17 months of age has been performed. This analysis showed 35 percent efficacy over a follow-up period ranging between 0 and 22 months (average 11.5 months). The RTS,S malaria vaccine candidate is still under development. Further information about the longer-term protective effects of the vaccine, 30 months after the third dose, should be available by the end of 2014. This will provide evidence for national public health and regulatory authorities, as well as international public health organizations, to evaluate the benefits and risks of RTS,S. The vaccine is being developed in partnership by GlaxoSmithKline and the PATH Malaria Vaccine Initiative, together with prominent African research centers. Source: EurekAlert! 10/18/11

Patient Recruitment Completed for International Breast Cancer Prognosis Study

The European Organization for Research and Treatment of Cancer (EORTC), Breast International Group (BIG), and Agendia in October announced the completion of patient registration for the EORTC 10041/BIG3-04 MINDACT (Microarray In Node negative and 1-3 positive lymph node Disease may Avoid Chemotherapy Trial) study. More than 6,600 patients in 111 institutions across nine countries have been enrolled in this trial. Genomic risk profiling lies at the heart of personalized management of cancer. MINDACT is investigating the added clinical value of Mammaprint(TM) to standard clinicopathological criteria for the accurate selection of breast cancer patients for adjuvant chemotherapy. The study aims to provide further evidence that early breast cancer patients with a low recurrence risk genomic profile by Mammaprint may not need chemotherapy. This would spare patients from burdensome side effects without increasing the risk of metastasis or reducing survival. The study is also designed to show whether MammaPrint can predict patient response to specific therapies. Commercialized by Agendia, MammaPrint has been cleared by the U.S. Food and Drug Administration as a prognostic tool identifying patients at low risk of metastasis, and can already be used across the spectrum of breast cancer cases for this purpose (including ER positive and negative, and lymph node negative and positive). It is being tested in MINDACT to provide large-scale prospective validation of its clinical utility. MINDACT is the largest European randomized prospective trial evaluating the clinical value of a genomic profile for risk assessment and adjuvant chemotherapy prescription for breast cancer. The trial's complex logistics, including real-time collection of frozen tumor tissue, were proven feasible in a multinational, multicenter setting. Based upon patients' risk of recurrence classification by MammaPrint and clinicopathological criteria, they are offered adjuvant chemotherapy (a nonmandatory randomization between commonly administered anthracycline-based regimens and the study combination of docetaxel plus capecitabine). Endocrine treatment is also offered to the patients whose tumors express hormone receptors (a nonmandatory randomization between letrozole and tamoxifen followed by letrozole). The entire genomic profile of each patient's tumor is also being analyzed, and this could allow research groups involved in the consortium to find new, specific companion diagnostics for the drugs administered in the trial. Agendia holds exclusive commercial rights to new RNA-based companion diagnostics that result from the trial, but research using biological samples / clinical data is open to the entire scientific community. MINDACT, which involved sites in the Netherlands, France, Germany, Belgium, Spain, Italy, U.K., Slovenia, and Switzerland, began recruiting patients in 2007, and its first results are expected in approximately three years. Source: PRNewswire 10/18/11

New Drug Found to Reduce Relapses in MS

A new oral drug has been shown in a large international clinical trial to significantly reduce the relapse rate of people with multiple sclerosis (MS) and to slow the progression of the disease. The results of the Phase III trial of the drug teriflunomide were published in a recent issue of The New England Journal of Medicine. "This could be a safe, effective, and convenient new therapy for [MS]," said Dr. Paul O'Connor, the principal investigator for the study and director of the Multiple Sclerosis Clinic at St. Michael's Hospital in Toronto, the largest and one of the most active MS research clinics in Canada. The study involved 1,088 MS patients between the ages of 18 and 55 who had at least one relapse in the previous year or at least two relapses in the previous two years. Each day, one-third of the patients received a placebo; one-third received a 7 mg dose of teriflunomide; and one-third received 14 mg of the drug. The study lasted nearly two years, and found a nearly 31 percent reduction in relapses in patients taking the drug at either dose. The drug also increased the length of time before a patient relapsed and more patients taking it remained free of relapses. Progression of the disease was also reduced by almost 30 percent among those taking the 14 mg dose. MRIs showed that patients taking 14 mg of teriflunomide had a 69 percent reduction in the number of new abnormalities in their brains caused by MS. The reduction was 48 percent for those on the lower dose of the drug. Teriflunomide is manufactured by Sanofi, which funded the clinical trial. Further studies are under way to replicate the work of Dr. O'Connor's group and to determine the long-term effectiveness and safety of the drug. Source: EurekAlert! 10/5/11

First of Two Proof-of-Concept Trials Targets RPE Detachment Treatment

Lpath, Inc. has initiated dosing in its PEDigree clinical trial where iSONEP™ is being investigated as a treatment for retinal pigment epithelium detachment (RPE detachment or PED). Lpath entered into an agreement with Pfizer in 2010 that provides Pfizer an exclusive option for a worldwide license to develop and commercialize iSONEP. In this human proof-of-concept trial, Lpath plans to dose 32 subjects--16 at a lower dose and 16 at a higher dose--that have PED secondary to wet age-related macular degeneration (wet AMD) or polypoidal choroidal vasculopathy (PCV). PED is a potentially serious condition that is often part of the pathology of wet AMD and PCV, yet no drug has yet been approved to treat PED. Even though patients with PED were excluded from the Lucentis® pivotal trials, this drug is often used to treat such patients, but with incomplete success. As such, the prognosis for those suffering from PED continues to be poor. Subjects in the PEDigree trial will receive up to three monthly intravitreal injections of iSONEP. The primary safety endpoint is the tolerability of consecutive monthly injections, and the primary efficacy endpoint is the percentage of subjects that experience complete flattening of their PED. In Lpath's Phase I trial, where subjects with wet AMD received only one injection, iSONEP met its primary endpoint of being well tolerated in all 15 patients. It also succeeded in meeting a key secondary endpoint in that a positive biological effect--with a single dose--was observed in most patients, almost all of whom had failed to respond to Lucentis and/or Avastin® treatment. Lpath plans to soon begin another iSONEP trial, a double-blind, 160-subject human-proof-of-concept trial to study the efficacy and safety of iSONEP in the broader wet-AMD patient population. Source: Marketwire 9/29/11

Study Finds Device-Guided Respiratory Modulation Helps Heart Failure Patients

InterCure Ltd. in September announced that the European Journal of Heart Failure, a peer-reviewed medical journal of the European Society of Cardiology, published the results of a 72-patients, randomized, controlled study that demonstrated that device–guided respiratory modulation with RESPeRATE applied at the home setting can significantly relieve symptoms of heart failure in elderly patients. The study was conducted by Inger Ekman, MD, professor of medicine, Institute of Health and Care Sciences, the Sahlgrenska Academy, University of Gothenburg, Sweden, with funding from the Swedish Heart Lung Foundation. It was found that after four weeks of twice-daily, 20-minute, at-home treatment sessions with RESPeRATE, patients, who modified the breathing as directed by the device, demonstrated a reduction in the severity of chronic heart failure (CHF) and in dyspnea (shortness of breath), the major reason for seeking care in the CHF population. The observed reduction was significant by both its absolute mean and in comparison to a control group and/or with patients who did not modify breathing as directed by the device. RESPeRATE is the only Food and Drug Administration-cleared, CE-marked device indicated for the adjunctive treatment of hypertension. RESPeRATE has not been cleared for use in the treatment of heart failure in the United States, European Union, or elsewhere. Source: EurekAlert! 9/28/11

NIH Modifies VOICE HIV Prevention Study in Women

A large-scale clinical trial evaluating whether daily use of an oral tablet or vaginal gel containing antiretroviral drugs can prevent HIV infection in women is being modified because an interim review found that the study cannot show that one of the study products, oral tenofovir, marketed under the trade name Viread, is effective. An independent data and safety monitoring board (DSMB) recommended that the Vaginal and Oral Interventions to Control the Epidemic (VOICE) study discontinue evaluating tenofovir tablets because the study will be unable to show a difference in effect between tenofovir tablets and placebo tablets. The DSMB found no safety concerns with oral tenofovir, which is currently used to treat HIV, or with the other products that will continue to be investigated as the VOICE study proceeds. As the trial's primary sponsor, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), concurred with the DSMB's recommendation and will modify the study. Because the trial is continuing, the study data remain confidential and restricted to DSMB analysis. Given that data are unavailable, NIAID cannot speculate about why oral tenofovir did not show an effect among VOICE study participants. Begun in September 2009, the VOICE study, or MTN-003, involves more than 5,000 HIV-uninfected women in South Africa, Uganda, and Zimbabwe. The trial was designed to test the safety, effectiveness, and acceptability of two different HIV prevention strategies: an investigational microbicide gel containing tenofovir, and oral tablets containing tenofovir either alone or co-formulated with the drug emtricitabine. The tablets, known by the brand names Viread (tenofovir) and Truvada (tenofovir plus emtricitabine), have been taken daily in an approach known as pre-exposure prophylaxis, or PrEP. After its routine review of the study data on September 16, the DSMB recommended that the investigators stop evaluating oral tenofovir because the study would be unable to show that tenofovir tablets have a different effect than placebo tablets at preventing HIV infection among the study participants. The DSMB therefore recommended that the roughly 1,000 women in the oral tenofovir group stop taking the study product. Further, the DSMB recommended that the VOICE study continue as designed to evaluate tenofovir gel and oral Truvada. The study team will immediately begin to inform all VOICE participants of this new development and will soon begin the orderly discontinuation of the tenofovir tablets. Participants who were taking oral tenofovir will stop using the product at their next scheduled clinical site visit. They will then return eight weeks later for a final set of tests and procedures before exiting the study. At that visit, they will be provided information about where they can continue to receive HIV testing and counseling, contraception, and other medical and support services. The NIH-funded Microbicide Trials Network is conducting the study. Source: EurekAlert! 9/28/11 For another story on this topic, click here. 

Partial Clinical Hold Placed on Trial Due to Overdose

Immunomedics, Inc. in September announced that the company has been notified by the U.S. Food and Drug Administration (FDA) that a partial clinical hold has been placed on the company's Phase Ib/II clinical trial of clivatuzumab tetraxetan in patients with advanced pancreatic cancer, due to the administration of an incorrect dose to a patient enrolled at one of its trial sites. This decision by the FDA was not due to safety issues of the product, but was based on a single incident in which a patient undergoing retreatment following a prior successful therapy cycle was inadvertently administered a yttrium-90 (Y-90) dose higher than prescribed. After this error was discovered, no further doses were given to the patient, who remains on study with no critical toxicity. To date, there have been approximately 360 doses of clivatuzumab tetraxetan labeled with Y-90 successfully and correctly administered to almost 100 patients. In response to this development, Cynthia L. Sullivan, president and CEO of Immunomedics, said, "We are preparing the requested remediation documents for the agency to ensure that this single error by the radiopharmacy will not reoccur in our trial, so that the partial clinical hold can be lifted as soon as possible. We are also working closely with the FDA to ensure patients who are eligible for retreatment can go on to receive additional cycles of therapy, once the partial hold is lifted." Source: Globe Newswire 9/22/11

Center Launches Lung Cancer Trial

Patients at Virginia G. Piper Cancer Center Clinical Trials are the first in the nation to participate in a clinical trial to determine the safety, tolerability, and preliminary activity of an investigational drug that targets cell-signaling proteins associated with the most common form of lung cancer, as well as other forms of cancer such as lymphomas and neuroblastoma. The first patient on the study was administered the first dose of AP26113 at Virginia G. Piper Cancer Center Clinical Trials, and the trial is now enrolling additional patients. AP26113, discovered and being developed by ARIAD Pharmaceuticals Inc. of Cambridge, Mass., is a small molecule cancer therapy that targets the suppression of two oncogenes associated with non-small cell lung cancer (NSCLC): anaplastic lymphoma kinase (ALK), and epidermal growth factor receptor (EGFR). Oncogenes are those genes with the potential to cause cancer. The center is the first site in the country to open a Phase I trial with AP26113. By Phase II, the study could include more than 100 patients at 11 clinical trial sites. Identifying mutations or abnormalities in oncogenes associated with NSCLC can distinguish patients who are more likely to benefit from a targeted therapy. As many as 7 percent of NSCLC patients will have the abnormal ALK gene, and as many as 17 percent of patients with NSCLC in Western populations are EGFR positive. AP26113 is designed to overcome resistance to crizotinib and to an EGFR inhibitor called erlotinib, sold as Tarceva. Source: EurekAlert! 9/21/11

Two New Clinical Trials Initiated to Treat Brain Cancer

The Swedish Neuroscience Institute in September announced that the Ivy Brain Tumor Center has launched two separate clinical trials for treating the brain cancer glioblastoma multiforme. The first trial, sponsored by Northwest Biotherapeutics, is a Phase II study to investigate a personalized vaccine (DCVax) that uses a patient's own master immune cells, combined with biomarkers from that patient's tumor tissue, to activate the master immune cells so they can mobilize the full immune system to recognize and kill the tumor cells. This type of tumor vaccine is used to strengthen the patient's own immune system to fight off the recurrence of the disease. The second trial tests a new approach to measure the effectiveness of the drug, Temozolomide (TMZ), in its activity against a patient's tumor. This study is being done in partnership with Accium BioSciences. A goal for the trial is to identify patients who are poor responders to TMZ early in their treatments so that physicians can pinpoint and select more effective drug strategies for each patient. Source: PRNewswire 9/21/11

Site Opening Announced for Phase I/IIa Trial of Novel Cell Therapy

SanBio, Inc. in September announced the site initiation and opening of a Phase I/IIa clinical trial testing a novel cell therapy product, SB623, in patients suffering from disability resulting from ischemic stroke. The study is taking place at the University of Pittsburgh Medical Center in Pennsylvania. An additional study site is also open and recruiting patients at the Stanford University Medical Center in Palo Alto, Calif. SB623 has been shown to improve neurological behavior in preclinical models of stroke. In this study, safety and efficacy parameters will be evaluated, including improvements in motor function and cognitive status. The trial will evaluate 18 patients who have suffered an ischemic stroke within the past six to 24 months and have a motor neurological deficit. SB623 is a proprietary regenerative cell therapy consisting of cells derived from genetically engineered bone marrow stromal cells obtained from healthy adult donors. SB623 functions by producing proteins that aid the healing process. Source: PRNewswire 9/20/11

Planned Enrollment Completed in Phase II Multiple Sclerosis Trial

Adeona Pharmaceuticals, Inc. announced in September that the 150th patient has been enrolled in the randomized, double-blind, placebo-controlled, multicenter clinical trial of its Trimesta™ (oral estriol) drug candidate for relapsing-remitting multiple sclerosis (MS) in women, per the original protocol. The company also announced that Rhonda Voskuhl, MD, director of the MS program at the University of California, Los Angeles Department of Neurology and lead principal investigator of the Phase II trial, has funding available to continue enrollment at all 15 centers, therefore, increasing the power of the trial. It is anticipated that the remaining grant funding will allow for the enrollment of an additional 10 to 20 patients. Estriol has been approved and marketed for more than 40 years throughout Europe and Asia for the treatment of postmenopausal hot flashes. It has never been approved by the Food and Drug Administration for any indication in the United States. Source: PRNewswire 9/19/11

Phase III Data Show Oral Calcitonin Tablet Safe and Effective

Tarsa Therapeutics in September presented positive safety and efficacy data from its Phase III ORACAL trial of Ostora™, the company's oral recombinant salmon calcitonin tablet in development for the treatment of postmenopausal osteoporosis. These data were presented at the American Society for Bone and Mineral Research 2011 Annual Meeting by ORACAL investigator Neil Binkley, MD, associate professor of endocrinology and geriatrics at the University of Wisconsin School of Medicine and Public Health in Madison, Wis. The multinational, randomized, double-blind, double-dummy, placebo-controlled trial compared the tablet to commercially available, synthetic salmon calcitonin administered by nasal spray and to placebo. The trial enrolled 565 postmenopausal women in six countries with established osteoporosis. Earlier this year, Tarsa reported top-line efficacy and safety results from the ORACAL trial. The latest data show that Ostora achieved all of the efficacy endpoints in the trial and indicate that its safety profile did not substantially differ from nasal calcitonin or placebo. Calcitonin is approved for the treatment of postmenopausal osteoporosis, but its use has been limited by the fact that it is currently available only in intranasal and injectable forms. Tarsa is also conducting a double-blind Phase II study comparing the Ostora tablet to placebo in postmenopausal women who have low bone mass (osteopenia) and are at increased risk of fracture. This proof-of-concept study is evaluating the ability of oral calcitonin to prevent osteoporosis and maintain bone mass in this population. Source: EurekAlert! 9/18/11

Antibody Brings Relief to Many in Study of Most Serious Form of Childhood Arthritis

Novartis announced in September positive results of the first pivotal Phase III trial of ACZ885, a fully human monoclonal antibody that inhibits IL-1 beta, in patients with systemic juvenile idiopathic arthritis (SJIA), a rare and serious childhood auto-inflammatory disease. The results, presented at the 2011 European Pediatric Rheumatology Congress in Bruges, Belgium, showed all primary and secondary endpoints of the study were met. Most ACZ885 patients (83.7 percent) experienced at least a 30 percent improvement in symptoms versus 9.8 percent for placebo, and a third of ACZ885 patients (32.6 percent) achieved a 100 percent improvement versus none for placebo. SJIA affects less than one child per 100,000 worldwide. It is called "systemic" because the inflammation affects the whole body, as well as most of the joints. The condition is characterized by potentially life-long and recurrent arthritis flares, which can involve skin rash, daily spiking fever, joint pain, and swelling. The results of a second pivotal Phase III trial, aimed at determining whether ACZ885 can extend the time to next flare and reduce or eliminate corticosteroid use, will be presented later this year. Worldwide regulatory submissions for ACZ885 in SJIA are planned for 2012. The four-week, randomized, double-blind, placebo-controlled study involved 84 patients between the ages of 2 and 19 years with active SJIA. Patients were treated with either a single subcutaneous dose of ACZ885 (4 mg/kg, up to 300 mg) or placebo. ACZ885 is currently approved in the U.S. and other countries for a different disease state. Source: PRNewswire 9/16/11

Midpoint of Enrollment Reached in ACL Reconstruction Device Trial

Aperion Biologics, Inc. announced that it has reached the midpoint of patient enrollment and implantation in the company's clinical trial of its Z-Lig™ anterior cruciate ligament (ACL) reconstruction device for the treatment of ligament injuries of the knee. The randomized, multicenter study commenced in January 2011 in both Europe and South Africa to provide safety and performance data in the reconstruction of patients' knees with primary ACL ruptures. The 60-patient study results will be used to support regulatory commercialization approvals and clinical acceptance of the device in select markets outside the United States. The company hopes to have Z-Lig, a porcine-derived product, approved as the first biologic graft option for ligament reconstruction procedures not produced from human tissue. Source: PRNewswire 9/14/11

Positive Results Reported in Phase III Study of Diabetics with ED

VIVUS, Inc. in September presented positive results from the avanafil Phase III study in diabetics. In the REVIVE-Diabetes study (TA-302), male diabetics receiving avanafil had significant improvement in erectile function. Dr. Irwin Goldstein, director of sexual medicine at Alvarado Hospital in San Diego, Calif., presented the results of the study during the poster session at the 47th European Association for the Study of Diabetes Annual Meeting in Lisbon, Portugal. Results of the study have been previously reported, but this was the first public European presentation of avanafil safety and efficacy data in diabetic patients. The study included 390 patients with type 1 and type 2 diabetes treated over 12 weeks with avanafil 100 mg, 200 mg, or placebo. Diabetics are disproportionately affected by erectile dysfunction (ED), which can worsen with increased duration of disease, and these patients are often considered less responsive to therapy. This study population consisted of men with an average age of 58 years and a mean duration of diabetes of 11 years and ED of five to six years. The majority were type 2 diabetics, with approximately 10 percent having type 1 diabetes. Avanafil was associated with significant improvements in erectile function relative to placebo. Subgroup analyses demonstrated that improvements in the percentage of successful intercourse attempts with avanafil 100 mg and avanafil 200 mg were observed regardless of diabetes classification (type 1 or 2), duration of diabetes, or baseline ED severity. Successful intercourse was achieved in some subjects in 15 minutes or less after dosing with avanafil. Some subjects had successful intercourse more than six hours after dosing. Source: PRNewswire 9/13/11

Phase II Trial of Kinase Inhibitor Launched for Patients with Prostate Cancer

Oncothyreon Inc. in September announced enrollment of the first patient in a Phase II trial of PX-866 in patients with recurrent or metastatic castration-resistant prostate cancer. PX-866 is a small molecule compound designed to inhibit the activity of phosphatidylinositol-3-kinase (PI-3K), a component of an important cell survival signaling pathway. The open-label trial is being conducted by the NCIC Clinical Trials Group, Queen's University in Kingston, Canada. The trial will enroll approximately 40 patients with castration-resistant prostate cancer who have received no prior chemotherapy. The primary endpoint of this single-arm screening trial is the proportion of patients with lack of disease progression at 12 weeks from the initiation of therapy with PX-866. The company now has four clinical trials of PX-866 under way, evaluating the agent in a variety of treatment settings and tumor types. PX-866 is a pan inhibitor of the PI-3K/PTEN/AKT pathway, a critical cell signaling pathway that is activated in many types of human cancer. Aberrant activation and regulation of PI-3K is implicated in a large proportion of human cancers, where it leads to increased proliferation and inhibition of apoptosis (programmed cell death). Oncothyreon is conducting a broad development program of PX-866 as a single agent and in combination with other agents in multiple cancer types. Current trials include a Phase 1/2 trial of PX-866 in combination with cetuximab (Erbitux®) in patients with metastatic colorectal carcinoma or progressive, recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) and a Phase 1/2 trial of PX-866 in combination with the chemotherapeutic agent docetaxel in patients with locally advanced, recurrent or metastatic non-small cell lung cancer or SCCHN. In addition, the NCIC Clinical Trials Group is conducting two Phase 2 trials, the trial in patients with recurrent or metastatic castration- resistant prostate cancer described above and a trial in patients with glioblastoma multiforme that has recurred during or following primary therapy. Source: PRNewswire 9/12/11

Early-Stage Clinical Trial Starts in Down Syndrome

Roche in September announced the initiation of its first Phase I clinical trial to investigate the safety and tolerability of a molecule designed to address the cognitive and behavioral deficits associated with Down syndrome. According to the company, enhancing brain functions such as cognition and language in individuals with Down syndrome holds the promise to help these individuals conduct a more independent life. This may result from the improved ability to carry out every day's practical tasks such as finding an apartment, maintaining a job, or having a more fulfilling social life. These improvements can have a significant impact on functioning and quality of life of Down syndrome individuals as well as help reduce the burden for families, caregivers, and society. The study will target the recruitment of up to 33 adults between 18 and 30 years old in one or two countries. Based on animal models, an imbalance between excitatory and inhibitory neurotransmission has been proposed as being among the underlying causes of altered brain function in individuals with Down syndrome. Roche's investigational drug is being assessed for its ability to address this imbalance by targeting the GABAergic system. Source: PRNewswire 9/9/11

Minimally Invasive Procedure Fails to Improve Symptoms of Emphysema in Large Trial

A procedure that had shown early promise in alleviating the symptoms of severe emphysema has failed to replicate its initial success and shows no durable benefit in the first randomized trial of airway bypass, published in a special European Respiratory Society issue of The Lancet. Currently, there are few treatment options and no cure for the 6 million people worldwide affected by emphysema. Airway bypass was designed to reduce lung inflation and shortness of breath. During the procedure, new passages are created into the lungs to release trapped air, supported and reinforced with drug-eluting stents. A previous feasibility study in 35 patients reported a significant reduction in residual volume (RV; the amount of air remaining in the lungs after full exhalation) and improvement in dyspnoea (shortness of breath) six months after airway bypass. The EASE (Exhale airway stents for emphysema) trial was established to test the safety and efficacy of airway bypass in patients with severe emphysema. Between October 2006 and April 2009, 315 patients were enrolled from 38 specialist centers worldwide and randomly assigned to airway bypass (208) or sham procedure (107), and followed for up to 12 months. Both groups underwent bronchoscopy, but only the treatment group received the airway bypass procedure involving the placement of up to six stents. Despite a significant reduction in RV and increased forced vital capacity (FVC; the total amount of air breathed in and forced out of the lungs) one day after the procedure, these effects were no longer detectable at one month. At the end of six months, no differences were noted in FVC and a breathlessness test (Medical Research Council dyspnoea score) between the treatment groups. In attempting to explain the disappointing results, the authors suggest that a combination of factors could be to blame including passages that were created but not stented and stent blockage due to mucus. However, they point out that the study produced invaluable lessons that will inform future interventions, and provides a unique model for the conduct of randomized, sham-controlled studies on medical devices. Source: EurekAlert! 9/8/11

Interim Data from Menses Suppresser Support Liver Safety

Repros Therapeutics Inc. in September reported results from the lowest three doses of its ongoing Phase II study of oral Proellex assessing the drug's ability to stop menses while not affecting liver function. The study evaluates the impact of the drug on menstrual events, the primary efficacy measure, as well as liver function, the primary safety assessment. To date, daily oral doses of 1, 3, and 6 mg have been completed. Up to 12 subjects per group made weekly visits during a multiple week run-in period and a 10-week dosing period. At each visit during the dosing period, trough blood level samples were obtained to determine levels of Proellex in the blood. At both the 3 and 6 mg dosage, all women that exhibited trough levels of the drug during the at-home portion of the study stopped menstruation. Repros believes the 6 mg dose will provide for robust efficacy and a significant margin of safety compared to the highest dose tested in previous studies, 50 mg. At the baseline and end of study in clinic visits, all women exhibited consistent maximum combined concentrations of the parent molecule and primary metabolite as well as overall exposure for a given dose. Measuring trough blood level samples was also useful in determining whether women were compliant with the dosing schedule. Rigorous assessment of liver function was also conducted throughout the study, comparing changes in liver function via weekly assessments over the course of the dosing period to weekly assessments during the run-in period. No elevations of liver enzymes, different from the baseline period, were seen at any of the first three doses tested. Also, no dose-dependent elevations have been detected. The company is currently completing the 9 mg dosing group and will commence dosing of the highest strength, 12 mg, following outside drug safety monitoring reviews of liver function findings. As with the first three doses, there have been no safety concerns detected to date in the 9 mg dose group. Repros believes this study will be completed before year-end 2011, and will report overall results at that time. The company plans to request an end-of-Phase II study with the U.S. Food and Drug Administration. Given a successful outcome, Repros expects to resume Phase III studies after that meeting. Women on an effective dose of Proellex typically stop menstruating. The company has shown in several studies of both uterine fibroids and endometriosis that this effect bears directly on the symptoms of these conditions, such as excessive menstrual bleeding and menstrual pain. Source: Globe Newswire 9/7/11

Recruitment Completed for Phase IIb of Type II Diabetes Treatment

TWi Biotechnology, Inc. in September announced the successful patient recruitment for the multinational, multicenter, randomized, double-blind, placebo-controlled, dose-ranging Phase IIb clinical trial of AC-201 for the treatment of type II diabetes. A combined 240 patients from 13 U.S. sites and eight Taiwan sites have been enrolled to the trial. With six-month treatment and one-month follow-up, completion of the trial data analysis is expected in the early second quarter of 2012. The trial's primary endpoint is defined as the change in glycated hemoglobin A1c (HbA1c) from baseline compared to placebo after 24 weeks of treatment. The study is powered to demonstrate additional benefits by monitoring various secondary endpoints, including changes in lipid profile, body weight, blood pressure, and beta-cell function. Meanwhile, by measuring various biomarkers, the company is able to stratify different patient groups in terms of clinical response, so as to develop personalized, preventive, or therapeutic strategies. During the previous Phase IIa study, those patients with inadequate blood glucose control by multiple drug combinations of currently available oral antidiabetic drugs were treated with AC-201 as an add-on therapy. The Phase IIa proof-of-concept study showed a mean reduction of 0.63 percent for HbA1c (n=56, p<0.05) at the end of 24 weeks treatment period. AC-201 is the only orally available small molecule modulating the cytokine synthesis of IL-1Beta and in post-transcription and post-translation stage. Reduction of IL-1Beta has been demonstrated to be effective in treating a variety of inflammatory diseases, including arthritis, diabetic nephropathy, and diabetic mellitus. Source: PRNewswire 9/7/11

Final Patient Injected with Hair Follicle Cells in First-in-Human Trial

RepliCel Life Sciences Inc. in September reported that the final study participant has received injections of hair follicle cells prepared using RepliCel™ technology. This milestone marks the end of the treatment phase of the TS001-2009 clinical trial, in which a total of 19 participants received injections. To date, no serious adverse events have been reported post-injection. An interim analysis is scheduled to take place in the first quarter of 2012. In the next stage of the TS001-2009 trial, the post-injection follow-up period, subjects return to the study center to have their health closely monitored to ensure that there have been no adverse effects associated with receiving the injections and to determine the hair growth stimulating efficacy of the hair follicle cell injections. Once the final patient has completed his or her six-month follow-up visit, an interim analysis of all collected data will be performed to assess the primary outcome measure of the TS001-2009 study. The analysis will involve assessment of the local (at treatment sites) safety profile of autologous hair follicle cells compared to placebo as defined by adverse events with respect to their causality, incidence, severity, and seriousness. Secondary outcome measures of systemic (overall) safety (through review of adverse events in a similar fashion as described above) and efficacy (hair growth at treatment sites) will also be performed at this time. Subjects will participate in the post-injection follow-up period of the study until August 2013, and final analysis of safety data should be available in late 2013. This single-center study enrolled subjects with alopecia categorized as either vertex pattern type II or type III on the Ludwig Scale (female) or as type III vertex to type VI on the Norwood Scale (male). At the beginning of the trial, subjects provided blood samples to confirm their health status and biopsies were taken from their scalps, from which hair follicle cells were processed using RepliCel technology. Once cell processing was complete, subjects returned to the study center to have baseline measurements of their overall health and the health of their scalps. They then received injections of their own replicated cells (autologous cells) in medium (verum) and medium alone (placebo) into two preselected treatment areas in their scalps. Source: Marketwire 9/7/11

Positive Phase II Data Support Drug's Potential in Advanced Breast Cancer

Syndax Pharmaceuticals, Inc., announced in September that ENCORE 301, a randomized, placebo-controlled Phase II study of exemestane with and without entinostat hit its primary endpoint of an improvement in progression-free survival. The study showed that patients who received entinostat, a novel, oral, small molecule inhibitor of class I histone deacetylases, with the hormone therapy exemestane, lived longer without their disease getting worse than people who received exemestane alone. Safety and efficacy results from the trial were presented in a poster and an oral presentation at the American Society of Clinical Oncology Breast Cancer Symposium 2011 in San Francisco, Calif. The treatment reduced the risk of disease progression by 27 percent and yielded an improvement in overall survival for postmenopausal women with estrogen-receptor positive metastatic breast cancer. Furthermore, in a subset of patients evaluated for a pharmacodynamic measure of entinostat's effect, researchers demonstrated for the first time with this class of agents evidence of an association of protein lysine hyperacetylation with clinical outcome. ENCORE 301 was a multicenter, randomized, double-blind, placebo-controlled study of exemestane with and without entinostat in 130 postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer, progressing on treatment with the nonsteroidal aromatase inhibitors anastrozole or letrozole. All patients had received prior hormonal therapy (one prior line = 42 percent; more than one prior line = 58 percent), and 33 percent had received prior chemotherapy in the advanced breast cancer setting. The company plans to enroll the first patient into a global, pivotal Phase III study in early 2012. Source: PRNewswire 9/6/11

Federal Approval Given for Clinical Trials of New Brain Cancer Treatment

DelMar Pharma in September announced that its Investigational New Drug application has been allowed by the U.S. Food and Drug Administration. The company is now able to initiate its planned clinical trial with its lead drug candidate, VAL-083, for the treatment of refractory glioblastoma multiforme (GBM). VAL-083 represents a first-in-class bifunctional alkylating agent. The drug benefits from prior extensive clinical research sponsored by the National Cancer Institute, and is approved as a cancer chemotherapeutic in China for the treatment of chronic myelogenous leukemia and solid tumors, including lung cancer. The clinical trial is a dose-escalating study that will evaluate the safety, tolerability, and antitumor activity of VAL-083 in GBM patients who have failed frontline therapy with Temodar® and second-line therapy with Avastin®. According to published data, approximately half of patients diagnosed with GBM will fail both front and second line therapy. Currently, there are no approved treatments for these patients. The company will now proceed with clinical site initiation and plans to begin patient recruitment activities during the fall of 2011. Further details on the clinical trial will be posted on the company's website once patient recruitment commences. Response to therapy and disease progression will be evaluated by MRI prior to each treatment cycle. An initial phase of the study will involve dose-escalation cohorts until a maximum tolerated dose (MTD) is established in the context of modern care. Once the modernized dosing regimen has been established, additional patients will be enrolled at the MTD (or other selected optimum dosing regimen). The company plans to conduct the study under the direction of Dr. Howard Burris at the Sarah Cannon Research Institute in Nashville, Tenn. Source: Marketwire 9/6/11

Diabetic Foot Ulcer Phase IIb Trial Completes Enrollment

Kuros Biosurgery AG announced in early September that it had completed recruitment in a Phase IIb clinical trial designed to investigate KUR-211 (Viz.I-020201) in the treatment of diabetic foot ulcers. This trial is a randomized, multicenter, controlled, parallel-group, dose-finding study to evaluate the efficacy and safety of KUR-211 used as an adjunct to standard of care in patients with diabetic foot ulcers. KUR-211 is a bioactive therapy intended for topical treatment to stimulate granulation tissue formation, which aids wound closure. The study evaluates the effects of KUR-211 applied twice a week for maximum 16 weeks in addition to standard of care versus standard of care alone. KUR-211 consists of a modified variant of platelet-derived growth factor incorporated into a fibrin sealant, and is applied to the wound as a foam. A total of 211 patients have been randomized and treated in more than 27 centers across Europe, including Russia. The primary endpoint of this study is percentage reduction in ulcer surface area after four weeks of treatment when compared to standard of care alone. Patients are followed for seven months following initial treatment. Kuros expects to report the outcome of this study around the middle of 2012. Kuros partnered with Baxter International Inc. for the development of KUR-211 under a collaboration and license agreement that was signed in 2005. Following the successful completion of this study, Kuros and Baxter will look for a partner to take over responsibility for the further development of KUR-211. Source: PRNewswire 9/1/11

Researchers Demonstrate Intravenous Delivery of Oncolytic Virus to Tumors

Jennerex, Inc. in late August announced the publication of clinical data on its lead product, JX-594, a proprietary, engineered oncolytic virus that is designed to selectively target and destroy cancer cells, in the journal Nature. For the first time in humans, an oncolytic virus was shown to reproducibly infect, replicate, and express transgene products within cancer tissue after intravenous infusion. Normal tissues were not significantly affected clinically, underscoring the designed selectivity of JX-594 for malignant tissue and safety of the product. The company and its partners are planning the further clinical development of JX-594 in liver, colorectal, and other cancer types, with the next step this year being the launch of the TRAVERSE trial, a global, randomized, controlled Phase IIb study in patients with hepatocellular carcinoma (liver cancer) having failed sorafenib (Nexavar®) treatment. JX-594 replication and engineered transgene expression within solid tumors was evaluated on a Phase I dose-escalation trial of intravenous infusion of JX-594. Twenty-three patients with advanced, treatment-refractory solid tumors were enrolled in one of six cohorts. Safety, antitumor activity, and pharmacokinetic parameters were also evaluated. JX-594 was generally well-tolerated, and dose escalation proceeded without dose-limiting toxicities. Cancer-selective and dose-related JX-594 delivery and replication in tumors were demonstrated in biopsies obtained eight to 10 days following infusion. In patients receiving higher doses whose tumor biopsies were evaluable for analysis, 87 percent exhibited JX-594 positivity, whereas JX-594 was not detected in biopsies collected from patients receiving lower doses. Phase I and II clinical trials in multiple cancer types to date have shown that JX-594, delivered either directly into tumors or systemically, induces tumor shrinkage and/or necrosis and is well-tolerated by patients (over 100 treated to date). Objective tumor responses have been demonstrated in a variety of cancers, including liver, colon, kidney, lung, and melanoma. JX-594 has a favorable safety profile with predictable and generally mild side effects that typically include flu-like symptoms that resolve in 48 to 72 hours. JX-594 was engineered for enhanced cancer selectivity by deleting its thymidine kinase (TK) gene, thus making it dependent on the cellular TK expressed at persistently high levels in cancer cells. To enhance product efficacy, JX-594 is also engineered to express the GM-CSF protein. GM-CSF complements the cancer cell lysis work of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown, and an antitumoral immune attack. Source: PRNewswire 8/31/11

Phase III Results of Test for Adult Growth Hormone Deficiency are Favorable

Aeterna Zentaris Inc. in late August announced favorable top-line results of its completed Phase III study with AEZS-130 as the first oral diagnostic test for adult growth hormone deficiency (AGHD). The results from nearly 100 subjects show that AEZS-130 reached its primary endpoint demonstrating a greater than 90 percent area-under-the-curve of the Receiver Operating Characteristic curve, which determines the level of specificity and sensitivity of the product. The company is currently proceeding with further detailed analyses of the data and preparing for a pre-New Drug Application meeting with the U.S. Food and Drug Administration (FDA) in the upcoming months. In the study, eight of the 10 newly enrolled AGHD patients were correctly classified by a prespecified peak growth hormone threshold level. The use of AEZS-130 was shown to be safe and well tolerated overall throughout the completion of this trial. The study was originally initiated to compare the performance of AEZS-130 against the then-available diagnostic growth hormone-releasing hormone Geref Diagnostic® + Arginine standard test. Geref Diagnostic was subsequently withdrawn from the market, worldwide, in 2008; the trial's sponsor, Ardana Biosciences, discontinued the study for financial reasons before it was completed. In 2009, Aeterna Zentaris entered into an agreement with administrators of Ardana and regained the rights to AEZS-130, and with the FDA, established the best way forward to complete this Phase III study and continue to utilize the data already obtained, in light of the loss of the original comparator. A Special Protocol Assessment granted by the FDA resulted in a modification of the original study, without altering the basic study design, so that the completed portion of the study and the new part of the study would provide a complete Phase III study. The modifications included an additional 30 normal control subjects being enrolled to match the AGHD patients from the original cohort; and an additional 20 subjects enrolled (10 AGHD patients and 10 matched normal control subjects) for the study's new part. Source: PRNewswire 8/30/11

Trial Will Evaluate Dosing of Anticoagulant for Patients with Mechanical Heart Valves

Boehringer Ingelheim Pharmaceuticals, Inc. in August announced plans to launch RE-ALIGN™, a global Phase II trial evaluating the safety and pharmacokinetics of dabigatran etexilate in 400 patients who have mechanical heart valves. The 12-week study will compare three doses of dabigatran etexilate (150 mg bid, 220 mg bid, and 300 mg bid) to warfarin in patients with both aortic valve replacements and mitral valve replacements. A RE-ALIGN extension study will evaluate the ongoing safety of dabigatran etexilate in this patient population for up to 84 months. Patients with mechanical heart valves require lifelong anticoagulation to help prevent blood clots from forming on or around the valve, which reduces stroke risk. Dabigatran etexilate was approved by the U.S. Food and Drug Administration in October 2010 as the first oral anticoagulant in more than 50 years to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF), and is sold under the brand name Pradaxa®. Findings from the Phase III RE-LY® trial showed that Pradaxa 150 mg taken twice daily significantly reduced stroke and systemic embolism by 35 percent beyond the reduction achieved with warfarin (dosed to international normalized ratio 2.0 to 3.0, mean time in therapeutic range = 64.4 percent) in patients with NVAF. Source: PRNewswire 8/26/11

Interim Analysis of Pediatric Cold and Flu Study Completed

Afexa Life Sciences Inc. in August announced the encouraging results of an interim analysis performed by an independent data monitoring committee for the currently in-progress COLD-FX® clinical trial in a pediatric population. The IDMC has completed a review of the data obtained to date and unanimously recommended that the study continue into the 2011/2012 cold and flu season. This multicenter, randomized, placebo-controlled, double-blind study is investigating the potential benefits of three day dosing of COLD-FX in reducing cold and flu symptoms in children. Recruitment of trial participants is continuing with a total of 500 children, aged 3 to 11, to be recruited from cities across Canada. Over the course of the trial, investigators estimate that approximately 60 percent of these children will develop cold or flu symptoms and be eligible to enter the study. Clinical trial participants are being randomized to take either a special formulation of COLD-FX for children or a placebo for three days, and are closely monitored for 14 days. The interim analysis was completed in a blinded fashion to evaluate the safety and efficacy and determine whether continuation of the trial was warranted. The results demonstrated a favorable trend and supported the independent recommendation to continue the trial to completion as per the study protocol. An earlier pilot study demonstrated the safety of COLD-FX in a pediatric population and provided early signals of efficacy, which were used to design the current study. The study has clearance from Health Canada and approval by all required Health Research Ethics Boards. Source: Marketwire 8/26/11

Commonly Prescribed Antibiotic Reduces Acute COPD Attacks

Adding a common antibiotic to the usual daily treatment regimen for chronic obstructive pulmonary disease (COPD) can reduce the occurrence of acute exacerbations and improve quality of life, reports new results from a clinical trial funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. The study appears in the August 25 issue of the New England Journal of Medicine. COPD exacerbations are sudden onsets of worsened cough, wheeze, and labored breathing that are typically induced by bacterial and/or viral infection. Azithromycin is already prescribed for a wide variety of bacterial infections, including pneumonia and strep throat. Previous research suggested that this antibiotic might work for COPD exacerbations, but this study was the first to enroll a large number of COPD patients and treat exacerbations with this drug over a long time. Participants had a history of exacerbations in the previous year or needed oxygen therapy. The 570 study participants who took 250 mg of azithromycin daily for a year in addition to their usual care averaged 1.48 acute COPD exacerbations annually, compared to 1.83 exacerbations for the 572 participants who received their usual care without azithromycin. The participants taking azithromycin also assessed their own breathing ability and overall well-being more favorably on questionnaires. The presence of microbes resistant to azithromycin increased in some patients, although no one developed a clinically evident infection. A small fraction of participants receiving azithromycin were found to have slight hearing loss, which is a known side effect of the drug. Azithromycin can also cause heart arrhythmias in susceptible people. No heart rhythm abnormalities were seen in study patients, though people with heightened risks for arrhythmias were not enrolled in the study. The study was carried out by the COPD Clinical Research Network, an NHLBI-funded consortium of research centers located throughout the U.S. that was established to study new treatments for COPD. Source: EurekAlert! 8/24/11

Phase III Clinical Program Initiated to Evaluate NSCLC-Associated Anorexia/Cachexia

Helsinn announced in August that its U.S. subsidiary, Helsinn Therapeutics, has enrolled the first patient in the company's pivotal Phase III clinical program of anamorelin HCl for the treatment of anorexia/cachexia in patients with advanced non-small cell lung cancer (NSCLC). The anamorelin clinical program includes two pivotal Phase III studies to be run in parallel, named ROMANA-1 and ROMANA-2. Each is a randomized, double-blind, placebo-controlled, multicenter global trial that is expected to enroll up to 477 patients. In addition, patients will have the option of continuing treatment in a 12-week safety extension study called ROMANA-3. The primary efficacy endpoints of ROMANA-1 and 2 include a measure of difference in the change in lean body mass and muscle strength in patients with advanced NSCLC-associated weight loss. Pharmacokinetic and additional safety measures will also be evaluated. In the U.S. and much of the rest of the world, there are no approved treatments for cancer-related cachexia, even though it affects a majority of cancer patients, including up to 60 percent of those with lung cancer. Earlier clinical studies suggest anamorelin may help address the significant loss of weight and physical function experienced by many patients undergoing treatment for cancer. Anamorelin HCl is an orally administered ghrelin receptor agonist and has been previously studied in approximately 500 subjects, including four completed Phase II trials involving 361 patients with cancer. Complete results from Phase II studies are expected to be published in the near future. Source: PRNewswire 8/23/11

First Procedure Performed in Phase II Stem Cell Trial for Lumbar Disc Repair

Mesoblast Limited in August announced that the first minimally invasive lumbar disc procedure had been successfully performed in the Phase II clinical trial of its proprietary adult Mesenchymal Precursor Cell (MPC) product for the treatment of low back pain and degenerative disc disease. The outpatient procedure lasted less than 20 minutes, with the patient fully awake and under light sedation. The patient was shortly discharged and there were no complications. The procedure was undertaken by leading spine surgeon, Kenneth Pettine, MD, at the Spine Institute and Loveland Surgery Center in Colorado, a United States Spine Center of Excellence. Dr. Pettine is a founder of the Spine Institute and the coinventor of Medtronic's Maverick artificial lumbar disc device. Up to 15 percent of people in industrialized countries have chronic low back pain lasting more than six months. For those with progressive, severe, and debilitating pain due to ongoing progression of disc degeneration, the only option is major back surgery involving artificial disc replacement or spinal fusion. Both types of surgery are associated with significant risks, and the avoidance of surgery is a major objective of new treatments for degenerative disease of the spine. In preclinical trials, a single minimally invasive injection of Mesoblast's allogeneic MPCs into severely damaged intervertebral discs resulted in significant reversal of the degenerative process, regrowth of disc cartilage, and sustained normalization of disc pathology, anatomy, and function for at least six months. Mesoblast's trial, which was cleared by the U.S. Food and Drug Administration in July, will enroll 100 patients with chronic low back pain due to lumbar disc degeneration in 15 centers across the United States and Australia, comparing outcomes at six months in 60 patients receiving MPC injections against 40 patients receiving control injections. Source: PRNewswire 8/22/11

Results Show Treatment Helps Prevent Kidney Injury from Imaging

PLC Systems Inc. in August announced that final results from the REMEDIAL II investigator-sponsored clinical trial of RenalGuard® in Italy have been published online in Circulation, and will appear in the September 2011 issue of the publication. The results from this trial showed that RenalGuard is superior to the current standard of care at preventing contrast-induced nephropathy (CIN) (acute kidney injury) and in-hospital dialysis in high-risk patients undergoing certain imaging procedures. In this trial, the investigators discovered that patients treated with RenalGuard and N-acetylcysteine (NAC) developed CIN, a serious and potentially fatal condition, at a much lower rate than patients in the control group who were treated with an infusion of sodium bicarbonate and NAC. Sodium bicarbonate plus NAC remains the current standard of care for the prevention of CIN in many healthcare institutions worldwide. The published results cover data from 294 patients with chronic kidney disease who underwent elective catheterization procedures for diagnostic imaging. The primary endpoint for the study used a definition of CIN as a rise in serum creatinine (SCr) of 0.3mg/dl over the patient's baseline reading. The RenalGuard-treated group had a CIN incidence rate 46 percent lower than the control group using this definition of CIN. In secondary endpoints, there was a 60 percent reduction in CIN in the RenalGuard-treated group compared to the control group when defining CIN as a 0.5mg/dl absolute rise in SCr and an 80 percent reduction of CIN in the RenalGuard-treated group over the control group when defining CIN as a 25 percent rise over baseline SCr. The trial also found that RenalGuard Therapy significantly reduced the need for in-hospital dialysis in high-risk patients. In the control group, seven (4.8 percent) of these patients required some level of dialysis. Only one patient (0.7 percent), or 85 percent fewer, in the RenalGuard-treated group required dialysis. Source: PRNewswire 8/18/11

First Clinical Studies Show Drug's Potential for Treating Heart Failure

A novel drug that activates a protein that increases the contraction of heart muscle could lead to a new approach to treating systolic heart failure (SHF), a condition characterised by the inability of the heart to contract strongly enough. The results of the first two clinical studies involving the drug omecamtiv mecarbil, published in a special European Society of Cardiology issue of The Lancet, suggest that it could be a promising treatment for SHF, which currently affects about 20 million people in the U.S. and Europe and leads to at least 4 million admissions to hospital each year. Omecamtiv mecarbil was designed by a team lead by Fady Malik from Cytokinetics Inc. in the U.S. to activate cardiac myosin, a motor protein in heart muscle cells that generates the force required for heart muscle to contract. In preclinical studies, omecamtiv mecarbil improved the strength of each heart muscle contraction, increasing the duration of the contraction and the volume of blood moved, without increasing oxygen consumption. But until now, whether this unique mechanism could be translated into humans was not known. John Teerlink from San Francisco Veterans Affairs Medical Center and colleagues report the first trial of omecamtiv mecarbil in humans, which was designed to establish the maximum tolerated dose and demonstrate an effect in people. Omecamtiv mecarbil or placebo was given once a week as a six-hour intravenous infusion to 34 healthy men for four weeks. Each sequence consisted of three ascending omecamtiv mecarbil doses (ranging from 0.005 to 1.0 mg/kg per hour) and a placebo infusion. The maximum tolerated dose was 0.5 mg/kg per hour. Omecamtiv mecarbil increased stroke volume, ejection fraction, and fractional shortening compared to placebo. Increases in systolic ejection time and systolic function were directly proportional to escalating doses in omecamtiv mecarbil, with no significant adverse effects reported in doses up to 0.625 mg/kg per hour. In the first study of omecamtiv mecarbil in heart failure patients, a team led by John Cleland from University of Hull in the U.K. conducted a Phase II trial to investigate the effects of omecamtiv mecarbil given intravenously over two, 24, or 72 hours to 45 patients with stable heart failure who were already receiving standard treatment. Omecamtiv mecarbil gave a significant dose-dependent increase in several measures of the heart's pumping function, including increasing the duration of systole, stroke volume, and ejection fraction. A significant association between improving systolic function and increasing plasma concentration was also noted. Source: EurekAlert! 8/18/11

Company Receives FDA Clearance for Phase II Trial of JCV Treatment

Inhibikase Therapeutics, Inc. announced in August that it has received U.S. Food and Drug Administration (FDA) clearance to commence a Phase II proof-of-concept trial for its lead compound IkT-001. IkT-001, a host-directed kinase inhibitor, is intended to clear JC polyomavirus (JCV) infection, the causative agent of progressive multifocal leukoencephalopathy (PML). This trial will be conducted in multiple sclerosis (MS) patients on natalizumab (Tysabri®), a patient group that is at significant risk for developing the potentially fatal PML disease. JCV progresses to PML only in patients with chronic or drug-induced immune suppression, including patients diagnosed with clinical AIDS or who are receiving monoclonal antibody treatment for MS, lupus, rheumatoid arthritis, leukemia, or lymphoma. The trial will be a four-week, open-label, sequential-dose-ranging study of the compound's safety and its antiviral effects against JCV in 48 patients with a relapsing form of MS who receive Tysabri infusion therapy. In addition to closely monitoring the safety and pharmacokinetic profile of IkT-001, the study also will determine the potential antiviral effect of IkT-001 against JCV as measured by the suppression of urinary excretion of JCV. Led by Jeffrey English, MD, of the Multiple Sclerosis Center of Atlanta, the study will be performed at three to five U.S. treatment centers for MS. All participating centers must be registered with the TOUCH Program for the prescription and infusion of Tysabir to patients with MS. Source: PRNewswire 8/16/11

Phase I Study Launched to Investigate Drug for Hereditary Inclusion Body Myopathy

Ultragenyx Pharmaceutical Inc. in August announced the dosing of the first patient in a Phase I study of UX001 for hereditary inclusion body myopathy (HIBM). UX001 is an extended-release formulation of sialic acid intended as a substrate replacement therapy for HIBM, a severe, progressive, genetic neuromuscular disease caused by sialic acid deficiency. UX001 is the first program from the company's pipeline to enter the clinic since its founding in 2010. The study will evaluate the pharmacokinetics and safety of UX001 in 24 HIBM patients at two centers in New York and Los Angeles. The study will test four different single-dose levels in each group of six subjects. Subjects will then undergo repeat dosing at three dose levels over seven days to establish the steady-state pharmacokinetics and safety of repeat doses of UX001. Ultragenyx anticipates data from the study in late 2011. HIBM, which is also known as distal myopathy with rimmed vacuoles and Nonaka disease, is a severe, adult-onset muscle disease caused by a defect in an enzyme responsible for the first step of sialic acid biosynthesis. With deficiency of this enzyme, the patient's muscles are deficient in sialic acid needed for the synthesis of proteins and fats. Patients with HIBM typically begin to have weakness and abnormal walking at 18 to 30 years of age. Over the ensuing 10 to 20 years, many patients progressively lose significant functional ability and become wheelchair-bound. There are no current treatments for HIBM. Source: PRNewswire 8/15/11

Phase I Breast Cancer Vaccine Trial to Launch

TapImmune Inc. announced in August that, following the Food and Drug Administration's approval of its Investigational New Drug application, the company will sponsor a Phase I HER-2/neu targeted therapeutic vaccine trial in HER-2/neu positive breast cancer patients at the Mayo Clinic. The trial stems from a technology license option and sponsored research agreements between Mayo Clinic and TapImmune, and is based on research on novel immunogenic peptide epitopes of the HER-2/neu antigen discovered in breast cancer patients with pre-existing immunity to HER-2/neu. The goal will be to determine whether the treatment can boost immunity to HER-2/neu in patients, hopefully paving the way to asking whether vaccination blocks tumors in humans. In the upcoming trial, HER-2/neu positive breast cancer patients will be given the vaccine mixed with GM-CSF as an adjuvant to enhance immunity. The trial aims to evaluate the safety of this vaccine as well as immune responses, and represents the first step in the development of a novel HER-2/neu vaccine that augments both CD4 T-helper cells and CD8 cytotoxic T-cells. It is due to commence recruitment in the fourth quarter of 2011. Under the terms of the technology license option agreement with the Mayo Clinic, TapImmune has an exclusive worldwide option to become the exclusive licensee for sale of any resulting commercial vaccines. Source: Globe Newswire 8/11/11

Company to Start Trial of Oral Mycobacterium Vaccae in TB Patients

Immune Network Ltd. reports that its business partner Immunitor has launched a Phase II clinical trial of a novel anti-tuberculosis (TB) immunotherapy consisting of orally delivered, heat-inactivated Mycobacterium vaccae. The new tableted preparation was formulated according to clinically validated proprietary technology developed by Immunitor. In extensive worldwide studies conducted during the past 30 years, the injectable version of M. vaccae has shown activity against drug-resistant TB and TB with HIV co-infection. However, due to inconvenience associated with invasive delivery of M. vaccae, which leaves permanent skin scars, coupled with infrequent dosing schedule, occasionally producing less-than-desired activity, the new oral formula of M. vaccae has been designed. The new pill formulation of M. vaccae as adjunct immunotherapy will be initially tested for one month in 20 individuals diagnosed with TB to determine whether it enhances the pharmacological activity of anti-TB drugs. These results will be compared to the control group, where patients will receive TB drugs along with placebo pills. Immunitor has built considerable experience in conducting such trials, and had recently completed a 120-patient, placebo-controlled Phase II trial with a similar oral immune modulator. Source: Globe Newswire 8/10/11

Phase II Trial Shows Positive Results in Carcinoid Syndrome

Lexicon Pharmaceuticals, Inc. announced positive, top-line, proof-of-concept data from its recently completed Phase II study in carcinoid syndrome with LX1032, telotristat etiprate. Carcinoid syndrome is a chronic condition caused by neuroendocrine tumors that usually originate from the gastrointestinal tract. It is characterized by severe diarrhea and flushing episodes with long-term consequences, including malnutrition, heart disease, and death. Symptoms of carcinoid syndrome have been linked to excess production of serotonin by metastatic tumor cells. Telotristat etiprate is designed to reduce serotonin production. Based on the positive results of this U.S. study, as well as encouraging observations from a clinical trial in Europe, the company intends to discuss a Phase III development plan for carcinoid syndrome with the Food and Drug Administration. The randomized, double-blind, placebo-controlled study was conducted in the United States in 23 patients with carcinoid syndrome who were refractory to currently available therapy. Patients in the study had metastatic carcinoid disease and were experiencing an average of about six bowel movements per day at baseline. Patients received either placebo (n=5) or one of four doses of telotristat etiprate (n=18) daily for 28 days. The primary endpoint of the study was safety and tolerability. Efficacy measures included change in bowel movement frequency, relief of symptoms, and reduction in serotonin synthesis. Five telotristat etiprate patients achieved clinical responses characterized by reductions of at least 30 percent in the number of bowel movements per day for two weeks or more during the study. Six telotristat etiprate patients reported adequate relief of carcinoid symptoms at the end of the study. There were nine telotristat etiprate patients with a complete biochemical response defined as a reduction of at least 50 percent in urinary 5-HIAA, a biomarker of serotonin synthesis. No patients on placebo experienced a clinical response, adequate relief of symptoms, or biochemical response during the study. Preliminary data were also reported from a separate, ongoing, open-label, single-arm study of telotristat etiprate in Europe. To date, five out of six patients with refractory carcinoid syndrome have experienced sustained reductions of at least 30 percent in bowel movement frequency when treated with telotristat etiprate. Source: PRNewswire 8/9/11

Cell-Based Therapy Does Well in Phase IIb Venous Leg Ulcer Study

Healthpoint Biotherapeutics in August announced positive top-line results for its Phase IIb clinical trial investigating the efficacy of HP802-247 in venous leg ulcers. HP802-247 is an investigational allogeneic living cell suspension containing keratinocytes and fibroblasts. The study was designed to determine the potential effectiveness of two cell concentrations and two dosing frequencies of HP802-247, when combined with standard care, compared to control plus standard care, in healing venous leg ulcers over a 12-week treatment period. The control in this trial was the self-assembling fibrin matrix that is part of the HP802-247 formulation, and which creates a provisional extracellular matrix in the wound. Overall, HP802-247 achieved statistical significance, as compared to control plus standard care, in both the primary and secondary endpoints: average percent change from baseline in the target wound area over the 12-week double-blind treatment, and time in days to complete wound closure from baseline. Statistical significance was also achieved for percent change from baseline in the target wound area at 10 of the 12 double-blind evaluation visits, and proportion of complete wound closure at nine of the 12 double-blind evaluation visits. Approximately 70 percent of subjects in the active treatment group receiving the optimal observed dose achieved complete wound closure at 12 weeks, compared to 46 percent in the fibrin control group, suggesting that the odds of healing are 2.75 times greater for the cell-treated subjects compared to those receiving the fibrin matrix alone. The randomized, dose-finding study involved subjects 18 years of age and older with venous leg ulcers of at least six weeks, but not more than 24 months duration, and between 2 cm(2) and 12 cm(2) in area at presentation. A total of 228 subjects were enrolled across 35 investigational centers in the United States and randomized into one of four active treatment groups (n=46, 43, 44, 45) or control plus standard care (n=50). HP802-247 is an investigational allogeneic living cell suspension that consists of two components that are sprayed sequentially on the wound bed at the time of treatment: a fibrinogen solution and a cell preparation containing a mixture of growth arrested, living, allogeneic epidermal keratinocytes and dermal fibroblasts. Based on in vitro studies, HP802-247 is believed to release various growth and angiogenic factors into the microenvironment of the wound through administration of these living, metabolically active, but nonproliferating cells that are trapped on the wound surface in a thin fibrin matrix. The secreted growth and angiogenic factors are anticipated to stimulate the patient's own cells to heal the wound. Source: PRNewswire 8/4/11

600th Patient Enrolled in Phase III Liver Cancer Trial

Celsion Corp. in August announced that it has reached its preplanned enrollment objective of 600 patients in the company's pivotal, Phase III HEAT study, a multinational, randomized, double-blind, placebo-controlled clinical trial of ThermoDox® in combination with radio frequency ablation for the treatment of primary liver cancer. The enrollment objective was established to ensure that the study's primary end point, progression-free survival (PFS), can be achieved with adequate statistical power and is one of two triggers for an interim efficacy analysis by the study's independent data monitoring committee. The second trigger is the confirmation of 190 PFS events in the study population. The HEAT study is being conducted under a U.S. Food and Drug Administration (FDA) Special Protocol Assessment, has received FDA Fast Track Designation, and has been designated as a Priority Trial for primary liver cancer by the National Institutes of Health. The HEAT study is the largest clinical trial ever conducted in intermediate hepatocellular carcinoma, an aggressive, deadly disease. Consistent with the company's global regulatory strategy, Celsion is continuing to enroll patients in the HEAT study in order to randomize at least 200 patients in China, a requirement for registrational filing in China. In addition to meeting the FDA enrollment objective, the HEAT study has also enrolled a sufficient number of patients to support registrational filings in South Korea and Taiwan. Continued enrollment will have no effect on the timing for the preplanned interim analysis, and has the potential to improve the time to final data. Source: Marketwire 8/3/11

FDA Approves Pivotal Study in Obstructive Sleep Apnea

Apnex Medical, Inc. received an Investigational Device Exemption approval from the U.S. Food and Drug Administration (FDA) to begin a clinical study to evaluate the safety and effectiveness of its Hypoglossal Nerve Stimulation (HGNS®) system to treat obstructive sleep apnea (OSA). Data from this clinical study are intended to support the Pre-Market Approval application for the system to the FDA. Many patients who suffer from OSA are unable to tolerate existing therapies, such as continuous positive airway pressure (CPAP). However, the HGNS system is an implantable therapy that is intended to work by activating the muscles in the upper airway to ensure that the airway remains open during sleep. The system detects the patient's breathing and delivers mild stimulation to the hypoglossal nerve, the nerve that controls the muscles of the tongue, to keep the airway open. The stimulation is timed to a patient's own breathing pattern. The system is designed to work only when the patient is asleep through a handheld controller. The prospective, randomized, multicenter trialis being conducted in leading medical centers in the United States, Europe, and Australia. The trial is designed to demonstrate the safety and effectiveness of the HGNS therapy in treating patients with moderate to severe OSA. To be enrolled in the study, patients must not have received lasting benefit from CPAP or other OSA treatments. Source: PRNewswire 8/2/11

Clinical Hold Announced on Phase III Lung Infection Trials

Insmed Inc. in early August announced that the U.S. Food and Drug Administration (FDA) has notified the company that the agency has placed a clinical hold on Insmed's Phase III clinical trials for ARIKACE® (liposomal amikacin for inhalation) in cystic fibrosis (CF) patients with Pseudomonas lung infections and patients with nontuberculous mycobacterial lung disease. A clinical hold is a notification issued by FDA to the sponsor to delay a proposed clinical trial or suspend an ongoing clinical trial. The company has been informed by FDA that this decision was based on an initial review of the interim results of a long-term rat inhalation carcinogenicity study, recently reported to the agency by Insmed, with ARIKACE. In this study, rats received daily doses of ARIKACE by inhalation for up to two years. FDA has requested additional information on ARIKACE and data from the rat study. At the time of the announcement, Insmed anticipated being able to supply the currently requested information and data within the next 30 days. As a result of the clinical hold, the company has suspended initiation of the ARIKACE Phase III clinical trial programs, including the recruitment and enrollment of patients. To date, no patients have been dosed in the pending clinical trials. The clinical hold will remain in effect at least until FDA reviews the information and data that are provided by Insmed. Source: PRNewswire 8/1/11

First Trial in Phase III Program for Dry Eye Disease Reports Results

ISTA Pharmaceuticals, Inc. in late July announced top-line results from the first of its two Phase III studies to evaluate the short-term safety and efficacy of two concentrations of REMURA™ (bromfenac ophthalmic solution for dry eye) in alleviating the signs and symptoms of dry eye disease. The company's Phase III safety and efficacy program, which consists of two studies known as EAST and WEST, is being conducted under a Special Protocol Assessment (SPA) agreed upon with the U.S. Food and Drug Administration. The new top-line results are from the WEST study; the EAST study is now fully enrolled and the company expects to announce top-line results from the EAST study during fourth quarter of 2011. According to preliminary analysis of the top-line results from the WEST study, while REMURA was highly effective in treating a sign and symptom of dry eye, it was not statistically significantly better than placebo, a common outcome reported in studies testing other dry eye therapies. From baseline, both concentrations of REMURA and the placebo showed highly statistically significant improvement in one sign and one symptom. The coprimary end-points identified in the SPA require REMURA to achieve a statistically significant difference from placebo, not baseline, which was not achieved in the WEST Study. Together, the studies are designed to enroll a total of approximately 1,000 patients with mild or moderate dry eye disease, randomized on a 1:1:1 basis to receive one of the two bromfenac dose levels, or placebo, in both eyes, twice daily, for 42 days, with a safety follow-up visit 10 days after dosing ends. The WEST study enrolled a total of 420 patients, 140 in each of the three arms. Source: Marketwire 7/28/11

IBS Drug Candidate Completes Phase I Trial

Lexicon Pharmaceuticals, Inc. announced in July that it had successfully completed a Phase I clinical trial of LX1033, an orally delivered small molecule drug candidate for diarrhea-predominant irritable bowel syndrome (IBS-d). Lexicon plans to move LX1033 forward into a Phase II study in patients with IBS-d. Top-line results demonstrated that LX1033 was well-tolerated at all doses and produced a statistically significant reduction in serotonin synthesis compared to placebo, as measured by both plasma and urinary 5-hydroxyindoleacetic acid (5-HIAA), a biomarker for serotonin synthesis. Importantly, a greater reduction in serotonin synthesis was achieved with lower and less frequent dosing and at lower drug exposure levels than was observed with Lexicon's first-generation serotonin synthesis inhibitor, LX1031, which had previously demonstrated clinical benefit to IBS patients in a Phase IIa clinical trial as measured by both global assessment of adequate relief and stool consistency. The Phase I trial was conducted as a randomized, placebo-controlled trial in healthy volunteers. In the multiple ascending-dose portion of the study, doses of 250 mg, 500 mg, and 750 mg given three times daily, as well as 1,000 mg given twice daily, were administered over the course of 14 days. There were eight healthy volunteers (six receiving active compound, two receiving placebo) in each dose group. Study endpoints included safety and tolerability, together with pharmacokinetic and pharmacodynamic parameters consisting of measures of both plasma and urinary 5-HIAA. LX1033 inhibits tryptophan hydroxylase, a key enzyme in the synthesis of serotonin. LX1033 is designed to act locally in the gastrointestinal tract by reducing the serotonin available for receptor activation, without affecting serotonin levels in the brain. Source: PRNewswire 7/28/11

Phase III Study Boosts Outlook for Oral Diagnostic Test for AGHD

Aeterna Zentaris Inc. in July announced completion of its Phase III study with AEZS-130 as the first oral diagnostic test for adult growth hormone deficiency (AGHD). The company is currently proceeding with detailed analyses of the data and preparing for a pre-New Drug Application (NDA) meeting with the U.S. Food and Drug Administration (FDA) in the upcoming months, which would be followed by the filing of a NDA for the registration of AEZS-130 in the United States. The study was originally initiated to compare the performance of AEZS-130 against the then-available diagnostic growth hormone-releasing hormone Geref Diagnostic® + Arginine standard test, which was subsequently withdrawn from the market, worldwide, in 2008; the trial's sponsor, Ardana Biosciences, discontinued the study for financial reasons before it was completed. In 2009, Aeterna Zentaris entered into an agreement with administrators of Ardana and regained the rights to AEZS-130. With the FDA, the company established the best way forward to complete the Phase III study and continue to utilize the data already obtained, in light of the loss of the original comparator. A Special Protocol Assessment granted by the FDA resulted in a modification of the original study without altering the basic study design, so that the completed portion of the study and the new part of the study would provide a complete Phase III study with a total of 100 subjects. AEZS-130, a ghrelin agonist, is a novel orally active small molecule that stimulates the secretion of growth hormone, after which a healthcare provider will measure how well the body responds to that stimulation based on the patient's growth hormone levels over a period of time. Low growth hormone levels, despite giving an effective stimulating agent, confirm a diagnosis of AGHD. AEZS-130 has been granted orphan-drug designation by the FDA for use as a diagnostic test for growth hormone deficiency. Source: PRNewswire 7/26/11

First Patient Enrolled in Drug-Coated Balloon Trial

Lutonix in July announced the first patient enrolled in the LEVANT 2 clinical trial, a global, multicenter, randomized trial evaluating the safety and efficacy of the Moxy™ drug-coated balloon compared to a standard angioplasty balloon for the treatment of peripheral arterial disease. The first case was performed at St. John's Hospital in Springfield, Ill., by Dr. Jeff Goldstein. LEVANT 2 is the first drug-coated balloon Investigational Device Exemption trial to be approved by the U.S. Food and Drug Administration, and is being conducted to support a Pre-Market Approval application for U.S. approval of the Moxy balloon. The trial is expected to randomize approximately 476 patients at up to 55 hospitals worldwide. LEVANT 2 is the largest randomized peripheral drug-coated balloon trial to date, and one of the largest peripheral vascular studies ever conducted. Randomized patients in LEVANT 2 will be followed for a total of five years and independent core laboratories will verify trial outcomes. The primary safety endpoint is a composite of freedom from all-cause perioperative death and freedom at one year from amputation, reintervention, and death. The primary efficacy endpoint is primary patency at one year. Dr. Kenneth Rosenfield (Massachusetts General Hospital in Boston) and Prof. Dierk Scheinert (Heart Center Leipzig/Park Hospital in Germany) are the coprincipal investigators of the trial. Drug-coated balloons have received growing attention in recent years, as physicians increasingly look for effective ways to treat diseased leg arteries without having to leave a permanent stent implant behind. Like the drug-eluting stents commonly used in the heart, the Moxy balloon delivers a powerful restenosis-fighting drug to the artery. However, unlike a stent, the Moxy balloon is removed from the body after use, leaving nothing but the drug behind in the artery. LEVANT 1 was a 101-patient randomized trial in which the Moxy balloon was compared to standard angioplasty for the treatment of diseased femoropopliteal arteries. The trial showed the Moxy balloon had the ability to safely and substantially inhibit restenosis. Source: PRNewswire 7/25/11

Data Demonstrate Significant Expression of Dystrophin in DMD Patients

AVI BioPharma, Inc. in July announced that data published in The Lancet from a Phase Ib/II study of eteplirsen, the company's exon-skipping therapy for the treatment of Duchenne muscular dystrophy (DMD), demonstrate that the treatment was well tolerated and was shown to induce statistically significant and dose-dependent improvements in dystrophin expression in patients. DMD is a genetic muscle wasting disease caused by the absence of functional dystrophin, an essential muscle protein. The primary objective of the 19-patient, 12-week, six-dose cohort study was to assess eteplirsen's safety and tolerability. Secondary objectives were assessments of the pharmacokinetic profile and ability to restore dystrophin expression. Eteplirsen induced exon 51 skipping in all cohorts, and novel dystrophin protein expression was observed in a dose-dependent manner. While results were variable among patients, the substantial, statistically significant new dystrophin expression was observed in the two highest dose cohorts. Moreover, novel dystrophin expression was accompanied by a significant reduction of inflammatory cell infiltrates in the two highest dose cohorts, including CD3, CD4, and CD8 inflammation markers, suggesting an alteration in the underlying degenerative disease process. The study was not designed to evaluate clinical benefit, and longer drug exposure is believed necessary to influence disease progression. Eteplirsen uses AVI's novel phosphorodiamidate morpholino oligomer (PMO)-based chemistry and proprietary exon-skipping technology to skip exon 51 of the dystrophin gene. By skipping exon 51, eteplirsen may restore the gene's ability to make a shorter, but still functional, form of dystrophin from mRNA. Promoting the synthesis of a truncated dystrophin protein is intended to improve, stabilize, or significantly slow the disease process and prolong and improve the quality of life for patients with DMD. AVI is also developing other PMO-based exon-skipping drug candidates intended to treat additional patients with DMD. Source: Marketwire 7/25/11

Antitumor Agent's Phase II Results Spur Global Development

Taiho Pharmaceutical Co., Ltd. announced in July the results of a randomized, Phase II clinical trial for the novel oral nucleoside antitumor agent TAS-102, which is under development by the company for metastatic colorectal cancer, at the 9th Annual Meeting of the Japanese Society of Medical Oncology held in Yokohama. The double-blind, placebo-controlled study with a primary outcome measure of overall survival involved 172 patients with refractory metastatic colorectal cancer who had received standard chemotherapy at least two or more regimens containing a fluoropyrimidine, irinotecan, and oxaliplatin. The results indicated that TAS-102 significantly improved overall survival compared to placebo (overall survival median: 9.0 months versus 6.6 months) and significantly reduced the risk of mortality. In light of these results, Taiho Pharmaceutical will proceed with global development of TAS-102, which is composed of a mixture of trifluorothymidine (FTD), which demonstrates antitumor effects through incorporation into DNA, and 5-chloro-6-(2-iminopyrrolidin-1-yl)-methyl-2,4(1H,3H)-pyrimidinedione hydrochloride, which inhibits the degradation of FTD. Phase I trials began in Japan in 2005, and the drug continues to be developed as a treatment for colorectal cancer refractory to standard chemotherapy and for which there is presently no established therapy. The Phase II trial was conducted at 20 medical institutions in Japan from August 2009 to April 2010. Source: PRNewswire 7/22/11

FDA Approves Wiskott Aldrich Gene Therapy Trial

The U.S. Food and Drug Administration (FDA) has approved the launching in the U.S. of a clinical trial for gene therapy for a rare immunodeficiency disease, Wiskott-Aldrich syndrome (WAS). After its implementation in Paris and London, this trial based on preclinical research performed at Genethon (Evry, France), is now going to be launched in Boston. It's one of the first international clinical trials using a gene therapy treatment for a rare disease. Earlier this year, Genethon, the not-for-profit biotherapy laboratory funded by the French Muscular Dystrophy Association, and Children's Hospital Boston announced that they had initiated a partnership to conduct such a trial. Genethon is sponsoring parallel trials at Great Ormond Street Hospital in London and Hospital Necker-Enfants Malades in Paris, and is supplying the vector for all clinical sites. In total, this trial will involve 15 patients, five for each site, who will be treated by 2013-14. The sites in London and Paris have already started treating patients under this protocol. Altogether, the WAS gene therapy trials in London, Paris, and Boston will constitute a unique multicenter collaboration to accelerate the testing of new advanced therapies for rare conditions. The Boston trial will be funded by the National Heart, Lung, and Blood Institute through its Gene Therapy Resource Program. The gene insertion of patient cells will be accomplished in the Connell O'Reilly Family Good Manufacturing facility at the Dana-Farber Cancer Institute in collaboration with the Center for Human Cell Therapy at Harvard Medical School. WAS is a rare primary immune deficiency disease causing significant bleeding due to low platelet count and increased incidence of serious infections. Source: PRNewswire 7/21/11

Phase II Trial Completed for the Treatment of Bladder Dysfunction in MS

Daval International in July announced the completion of the treatment period of its randomized, placebo-controlled, double-blind Phase II study treating patients with bladder dysfunction with AIMSPRO in secondary progressive multiple sclerosis (SPMS). Standard clinical measures and assessment scores recorded on patients who have MS, as well as novel biomarkers will be used to investigate safety, efficacy, and response to treatment. Daval expects to have the initial results from this trial by the end of the summer of 2011, with secondary and tertiary outcomes (biomarker data) being made available shortly thereafter. The study completion marks more than 10 years of research and development undertaken by Daval with AIMSPRO. Twenty patients participated in the crossover trial comparing AIMSPRO to placebo. The primary endpoint of the study is the change in average voided volume at weeks 0 to 4 and weeks 10 to 14, respectively. AIMSPRO is a subcutaneously delivered peptide/polyclonal "large biologic," technically described as hyperimmune caprine serum raised against an inactivated HIV IIIB viral lysate. AIMSPRO has demonstrated powerful and well-tolerated anti-inflammatory capabilities. AIMSPRO exhibits tri-partite functionality by targeting the HPA axis and other pathways, and by regulating several key intracellular protein kinases via a highly coordinated mechanism. Source: PRNewswire 7/20/11

Company Starts Phase II Study for Selective Nav1.7 Blocker

Convergence Pharmaceuticals Limited in July announced that the Phase II proof-of-concept study with CNV1014802 for treating pain associated with lumbosacral radiculopathy (LSR) has started. LSR is a common neuropathic pain condition caused by compression of the nerve roots in the lumbar region of the spine. Common features include pain radiating from the lower back down the legs, together with sensory and motor impairment in the lower limbs. LSR affects 3 to 5 percent of the global population, and there are no drug treatments currently approved for treating this type of neuropathic pain. The randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy and safety of orally administered CNV1014802, and incorporates a number of design features that the company says will enhance confidence in the outcome. The trial will run in four European countries, and results are expected in the second half of 2012. CNV1014802 is a novel small molecule, state-dependent sodium channel blocker that exhibits potency against the Nav1.7 sodium channel. It was recently validated as a key pain target by human genetic linkage. CNV1014802 has completed extensive Phase I studies with single and repeated doses in more than 150 healthy volunteers, demonstrating an excellent pharmacokinetic and safety profile. CNV1014802 also demonstrated an ideal pharmacokinetic profile together with excellent toleration at doses within the expected therapeutic range. Source: PRNewswire 7/19/11

Phase III Launched for Intranasal Drug for Seizure Clusters in Epilepsy

Upsher-Smith Laboratories, Inc. announced in July the initiation of a Phase III clinical trial to evaluate the safety and efficacy of USL261, an investigational intranasal midazolam, for the rescue treatment of seizures in patients on stable anti-epileptic drug regimens who require control of intermittent bouts of increased seizure activity, frequently referred to as seizure clusters. USL261 has been granted orphan drug designation for this use by the Food and Drug Administration (FDA). The randomized, double-blind, placebo-controlled study (ARTEMIS1) will compare intranasal midazolam, a benzodiazepine, to an intranasal placebo in males and females ages 14 to 65 years with a diagnosis of seizure clusters and who have a competent caregiver. The seizure clusters must have a pattern that is different from the individual's other noncluster seizure activity, and must be recognizable by a caregiver. USL261 may allow a caregiver to deliver an appropriate dose of the medication intranasally to an individual who is experiencing an intermittent bout of increased seizure activity. It is intended that this administration will not require an active inhalation by the patient. Currently, only one medication is FDA-approved for intermittent bouts of increased seizure activity, and it must be delivered rectally. Source: PRNewswire 7/18/11

Positive Results Seen for Oral Diabetes Treatment

A new peroxisome proliferator activated receptor agonist currently in development, DB959, will most likely be administered orally once a day, according to a presentation made by researchers recently at the American Diabetes Association’s 71st Scientific Sessions. This would make DB959 unique among medications that treat people with type 2 diabetes. A recently completed escalating dose study by DARA BioSciences, Inc. has tested the single-dose safety, tolerability, and pharmacokinetics of DB959. This first human trial was a randomized, placebo-controlled, double-blind study, and it enrolled 70 healthy volunteers aged 18 to 45 in groups of eight participants each. The first group of volunteers was given 2 mg of DB959. After ensuring that dose was well-tolerated, another group was given 5 mg, the next group was given 10 mg, and then subsequent groups received doses escalating up to 200 mg per day. Both active and placebo groups tolerated the drug equally at all doses; the few adverse effects that were shown were mild and not dose related. The pharmacokinetic parameters of the drug were consistent with once-a-day dosing. The drug’s half-life ranged from 14.8 to 19.9 hours over the tested dose range. Other measurements revealed that the drug was not excreted unchanged in urine, and the examination of a possible food effect revealed that a high fat meal only slightly delays the drug’s absorption. According to Mary K. Delmedico, PhD, and her coauthors, DB959 continues to show promise. In addition to demonstrating its long half-life, the current study found that the maximum tolerated single dose of the drug is more than 200 mg, which is approximately 10 times the anticipated therapeutic dose range. Source: Newswise 7/13/11

Phase II STEC Infection Trial Temporarily Suspended

Thallion Pharmaceuticals Inc. announced in July that it has temporarily suspended the screening and enrollment of the high-dose cohort of its Phase II SHIGATEC study as a precautionary measure due to a preliminary product out-of-specification finding observed during routine stability testing of its anti-Stx1 monoclonal antibody. "This voluntary action reflects our uncompromising view toward the safety and care of our patients," commented Dr. Allan Mandelzys, chief executive officer of Thallion. "Until we have more complete data to fully assess the situation, we determined that temporarily suspending enrollment is the appropriate and most conservative decision." The company, together with its development partner LFB Biotechnologies, is conducting a thorough analysis to better understand the nature of this finding over the coming weeks, and will communicate the results of its assessment promptly. Potential outcomes could range from removing the temporary suspension and continuing the study with the current clinical material or maintaining the enrollment suspension until a new lot of clinical material is manufactured. The randomized, double-blind, placebo-controlled trial will enroll 42 patients, aged six months to 18 years testing positive for STEC infection, distributed in two cohorts. The first cohort compares standard of care combined with a low dose of Shigamabs® (1 mg/kg/dose) versus standard of care with placebo. The second cohort will compare standard of care combined with a high dose of Shigamabs (3 mg/kg/dose) versus standard of care with placebo. The primary endpoints for the Phase II trial are safety and tolerability. Secondary endpoints include pharmacokinetics and objective measures of efficacy using single and composite endpoints. Shigamabs consists of two monoclonal antibodies designed to bind specifically and exclusively to the Shiga toxin 1 and Shiga toxin 2 toxins secreted by Shiga toxin- producing E. coli bacteria. STEC infections are primarily foodborne bacterial infections that cause serious health complications, particularly in young children and the elderly, and affect approximately 314,000 people annually in the industrialized world. There are no approved products available for the treatment of STEC infections. The Shigamabs antibodies, administered as a single intravenous injection, bind to their respective toxin and neutralize them by forming a complex that is absorbed and destroyed by the liver and spleen. Shigamabs has obtained orphan drug designation both in the U.S. and in Europe. Source: Marketwire 7/13/11

Completed Phase I Trial Targeted Neuroprotective Brain Injury and Stroke Treatment

Sinapis Pharma, Inc. announced that it has completed its first clinical trial in the development of its lead drug for the treatment of stroke and traumatic brain injury. The Phase I trial was conducted at Prism Research in St. Paul, Minn. This was a single-center, open-label, randomized, two-period, two-treatment, two-sequence, single-dose, crossover study of the safety and pharmacokinetics of oral and IV administration of methamphetamine HCl in six healthy volunteers. Subjects were randomized 1:1 to receive a single oral dose of methamphetamine HCl (5 mg Desoxyn® tablet) or a single IV dose of methamphetamine HCl (5 mL of 0.5 mg/mL methamphetamine HCl injection infused over one hour for a total dose of 2.5 mg), and then crossed over to the other treatment (i.e., IV or oral dose, respectively) after a 10-day washout period. Subjects received a single dose of study drug on the first day of each of the two treatment periods. The trial successfully demonstrated the safety of an IV infusion of methamphetamine and produced the IV infusion pharmacokinetics needed to initiate Phase IIa clinical studies in stroke patients. Sinapis plans to initiate its Phase IIa trial in stroke patients before year end. Source: PRNewswire 7/11/11

Review of Phase III Study in Primary Liver Cancer Recommends Continuation

Celsion Corp. in July announced that the independent data monitoring committee for the company's multinational, double-blind, placebo-controlled, pivotal Phase III clinical study of ThermoDox® in combination with radio frequency ablation (RFA) for primary liver cancer (the HEAT study), has completed a review of 535 randomized patients and unanimously recommended that the study continue according to protocol. The company also announced that enrollment in the HEAT study has reached 98 percent of the 600 patients necessary to ensure that its primary end point, progression-free survival, can be achieved with statistical significance. The study's design and statistical plan incorporate a preplanned interim efficacy analysis by the data monitoring committee (after patient enrollment is complete and 190 progression-free survival events are realized in the study population) with the intent of evaluating safety, efficacy, and futility to determine if there is overwhelming evidence of clinical benefit or a low probability of treatment success to continue, modify, or terminate the study. Completion of the interim analysis is expected by the end of the third quarter of 2011. ThermoDox is designed to concentrate doxorubicin in the margins surrounding the tumor, activating only in the presence of heat. The company's data indicate that the result is an increased treatment area, which may extend the cure rate of RFA to larger, more locally advanced tumors. Final data read out for the primary outcome measure is expected in mid-2012. Source: Marketwire 7/11/11

Multicenter Trial of Transoral and Transvaginal Gallbladder Removal Boosted by Grant

The Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR®), a joint effort of the American Society for Gastrointestinal Endoscopy and the Society of American Gastrointestinal and Endoscopic Surgeons, has announced a grant from Covidien to support the U.S. multicenter human trial on transoral and transvaginal cholecystectomies (gallbladder removal) using Natural Orifice Translumenal Endoscopic Surgery (NOTES®). The NOSCAR study uses the mouth or vagina as routes to the gallbladder. Rather than making up to five incisions in the abdominal wall, tools are passed down the mouth and through a hole created in the stomach (transoral/transgastric) or through the vagina (transvaginal). The prospective multicenter trial compares NOTES cholecystectomy versus conventional laparoscopic cholecystectomy. NOSCAR has granted funds to selected institutions to conduct these trials. Institutions participating in the trial have demonstrated a strong commitment to developing the basic science that forms the foundation of NOTES and have already performed human NOTES cases under an institutional review board protocol; approximately 200 patients will be enrolled in the clinical trial. "The human trials have already achieved very positive results, and we now have a total of five institutions and 35 patients participating in the trial," said Michael L. Kochman, MD, cochair of the NOSCAR Research Subcommittee. Source: EurekAlert! 7/8/11

Drug Nearly Doubles Progression-Free Survival in Phase III

In the first Phase III study to include Western lung cancer patients, first-line treatment with erlotinib (Tarceva) nearly doubled progression-free survival compared to chemotherapy, according to research presented at the 14th World Conference on Lung Cancer in Amsterdam. Erlotinib is a tyrosine kinase inhibitor (TKI) that targets the epidermal growth factor receptor (EGFR). Non-small cell lung cancer (NSCLC) patients with EGFR activating mutations tend to respond well to TKI therapy. "Although a growing body of evidence has been emerging about this type of lung cancer, almost all of the studies have been conducted in Asian patients, a group that historically has had significantly different results to NSCLC therapy compared to Western populations," said principal investigator Dr. Radj Gervais, MD, of the Centre François Baclesse in Caen, France. "EURTAC is the first Phase III study with first-line erlotinib in Western patients with this genetically distinct type of advanced NSCLC." Researchers tested more than 1,000 patients over a five-year-period to find a study population of 174 patients who were randomly assigned to receive erlotinib or platinum-based chemotherapy. The response rate to erlotinib was 54.5 percent, compared to 10.5 percent to chemotherapy, according to preliminary results. Progression-free survival in the erlotinib arm was 9.4 months, compared to 5.2 months in the chemotherapy arm. Median survival was 22.9 months in the erlotinib arm and 18.8 months in the chemotherapy arm. Source: EurekAlert! 7/5/11

Phase II/III Trial in Severe Sepsis Initiated

Agennix AG in late June announced that the first patient has been dosed in the Phase II part of the OASIS (Oral Talactoferrin in Severe Sepsis) trial, a multicenter, double-blind, randomized Phase II/III trial evaluating the oral immunotherapy talactoferrin for the treatment of severe sepsis. The OASIS trial is evaluating talactoferrin plus standard care compared to placebo plus standard care in adult patients with severe sepsis. The Phase II part of the trial is planned to enroll approximately 350 patients at clinical sites predominantly in Western Europe and North America. The study's primary objective is to determine the effect of talactoferrin on 28-day all-cause mortality. Secondary endpoints include three-month, six-month, and 12-month all-cause mortality. The study will also evaluate the safety and tolerability of talactoferrin in this patient population, and data will be collected to further elucidate the mechanism of action of talactoferrin. Talactoferrin is an oral immunotherapy that is being studied for the treatment of cancer and severe sepsis. Talactoferrin has demonstrated promising activity in randomized, double-blind, placebo-controlled Phase II studies in non-small cell lung cancer (NSCLC) and in severe sepsis. Two Phase III trials with talactoferrin in NSCLC are ongoing. The FORTIS-M trial, which completed enrollment in March 2011, is evaluating talactoferrin in NSCLC patients whose disease has progressed following two or more prior treatment regimens. A second Phase III trial (FORTIS-C) is evaluating talactoferrin in combination with the standard chemotherapy regimen, carboplatin/paclitaxel, in first-line NSCLC patients. Source: Marketwire 6/30/1

First Patient Treated in Phase Ib Osteoarthritis Trial in Australia

Ampio Pharmaceuticals, Inc. in July announced treatment of the first patient in the three-arm, placebo-controlled, 60-patient Phase Ib Ampion-In -Knee (AIK) trial in Australia. The active ingredient in Ampion™ has extensive worldwide patent protection, including composition of matter and use patents. The study is being conducted in patients diagnosed with a medical condition (pain and inflammation of the knee [osteoarthritis]), which the study drug is intended to alleviate and confirm the hypothesis that the current outcome benefit is compatible with the mechanism of action of the drug. In this study, Ampion (the low molecular fraction of commercial albumin preparation) is injected into the knees of patients with osteoarthritis of the knee in conjunction with standard therapy, including steroids, aiming to demonstrate a reduction in pain and improved range of motion compared to placebo. The observation period in this study is short (72 hours) hence, results of this trial are anticipated to be available in the short term. Ampion is a patented small molecule with nonsteroidal anti-inflammatory and analgesic properties that is naturally produced by humans in response to injury. Because it is present in commercially available human serum albumin (which has been given to millions of people over several decades) it can be considered to be a biological. Ampion may qualify as a new use for an existing drug with the potential of a shortened regulatory path compared to new drugs, because human serum albumin is approved for intravenous administration to patients. Source: PRNewswire 7/5/11

Positive Findings Reported from Phase IIb Metastatic Breast Cancer Trial

Accelerated Community Oncology Research Network, Inc. (ACORN) reported positive results of a large, double-blind, randomized Phase IIb trial in patients with breast cancer at the American Society of Clinical Oncology 47th annual meeting in Chicago in June. The study, managed by ACORN Research, evaluated a novel drug regimen for the treatment of locally advanced or metastatic breast cancer. The regimen, Nexavar® (sorafenib) tablets in combination with either Gemcitabine (Gemzar®) or Capecitabine (Xeloda®), found statistically significant improvement in progression-free survival. Forty investigative sites enrolled 160 patients over a three-year period. The study was conceived as one of a suite of trials collectively evaluating the addition of Nexavar to chemotherapy in different advanced disease settings. The results demonstrate activity for this antiangiogenic agent in patients who had progressed on bevacizumab-containing regimens. The trial was one of two studies sponsored by Onyx Pharmaceuticals with clinical research and site management services provided by ACORN Research. Nexavar is an antiangiogenic drug that works by decreasing blood flow to the tumor cells. This approach has been shown to be effective in other types of cancer, especially when combined with traditional chemotherapy. Nexavar is being codeveloped by Bayer HealthCare Pharmaceuticals Inc. and Onyx Pharmaceuticals Inc. Source: PRNewswire 6/30/11

Topline Results Fall Short in Phase II Chronic Low Back Pain Study

Endo Pharmaceuticals announced in June topline results from a Phase II study comparing the novel investigational drug axomadol to placebo in the treatment of patients with moderate to severe chronic low back pain. The results indicate that axomadol did not meet predetermined study end points. The company is currently completing additional analyses of the data and evaluating the path forward for the program. The study was a randomized, double-blind, two-arm, placebo-controlled, parallel-group design and included 236 patients with moderate to severe chronic low back pain. Axomadol was orally administered at doses ranging from 100 mg/day to 300 mg/day over a four-week period with a 12-week maintenance phase. The primary outcome measure was change in average pain intensity using a Numerical Rating Scale from baseline to final week of treatment for all patients receiving at least one dose of study drug. Endo licensed exclusive rights to develop and market axomadol in the United States and Canada from Grunenthal in February 2009. Source: PRNewswire 6/30/11

Studies Confirm Drug's Efficacy and Tolerability in Combination Therapy with Metformin

Boehringer Ingelheim and Lilly in June announced Phase III study results for linagliptin, demonstrating improved glycemic control in adults with type 2 diabetes whose blood glucose is not adequately controlled on current therapy. In one long-term study over two years evaluating linagliptin or glimepiride when added to metformin, linagliptin was effective at lowering blood glucose, as measured by haemoglobin A1C, but with relative weight loss, reduced incidence of hypoglycaemia, and few cardiovascular events. The results were presented at the 71st Annual American Diabetes Association Scientific Sessions in San Diego, Calif. A separate 24-week study evaluating linagliptin demonstrated mean placebo-corrected A1C reductions of up to 1.7 percent from baseline when linagliptin 2.5 mg twice daily (bid) was used in combination with metformin 1,000 mg bid in type 2 diabetes patients with insufficient glycemic control. The combination of linagliptin plus metformin was well-tolerated and improved glycemic control more than either medication when used alone. In the trial, there was no weight gain with the linagliptin plus metformin combination, and a very low risk of hypoglycaemia. In an open-label arm including patients with poor glycemic control (A1C at baseline >11 percent) linagliptin 2.5 mg twice daily (bid) in combination with metformin 1,000 mg bid achieved a reduction from baseline of A1C of 3.7 percent. Linagliptin was also evaluated in patients with varying degrees of renal function. A large pooled analysis of three randomized, placebo-controlled Phase III trials (n=2,141) showed that type 2 diabetes patients who received linagliptin had A1C reductions independent of their degree of renal function. In an additional study evaluating patients with severe renal impairment whose blood glucose was insufficiently controlled, linagliptin provided placebo-corrected A1C reduction of -0.6 percent after 12 weeks of treatment. Renal function remained stable over time and cardiovascular deaths in this high-risk population were low: one patient per arm. Source: EurekAlert! 6/28/11

Company Initiates Phase IIa Dose-Ranging Study for CKD Patients with Anemia

Akebia Therapeutics, Inc. in June announced that it had initiated dosing in patients for a Phase IIa dose-ranging study of AKB-6548 in stage 3 and 4 chronic kidney disease (CKD) patients. AKB-6548 is an orally bioavailable hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitor designed to increase the natural production of erythropoietin (EPO) and cause a controlled, gradual rise in hemoglobin in anemic patients. In a recently completed Phase IIa dose-escalation study, a controlled rise in hemoglobin and a corresponding decrease in ferritin were observed. Patients with CKD are often undertreated for anemia. The new randomized, double-blind, placebo-controlled, dose-range finding study is designed to evaluate the safety, tolerability, and pharmacokinetics of AKB-6548 in stage 3 and 4 CKD patients, and will enable the selection of a dose regimen to be used in future studies. Subjects will be randomized into five different dosing groups, and AKB-6548 will be administered orally on an outpatient basis once daily for 42 days. The study will enroll 100 subjects at multiple sites in the United States. Source: Marketwire 6/23/11

First Patient Enrolled in Phase II for Lactose Intolerance Treatment

Ritter Pharmaceuticals, Inc. announced in June that clinical investigators have enrolled the first patient in its randomized, double-blind, placebo-controlled Phase II study of RP-G28 in patients with symptoms associated with lactose intolerance. The study, which is being conducted by investigators in clinical sites in Honolulu, Hawaii and Dallas, Texas, is expected to enroll approximately 80 patients. The objectives of the study are to evaluate the efficacy, safety, and tolerability of RP-G28 in treating the symptoms of lactose intolerance. Ritter expects initial study results in the first quarter of 2012. Source: Marketwire 6/21/11

FDA Approves Phase I/II Trial for Ovarian Cancer Vaccine

Immunovaccine Inc. announced in June that the U.S. Food and Drug Administration (FDA) reviewed and cleared its Investigational New Drug application for a Phase I/II clinical study with DPX-Survivac, a therapeutic cancer vaccine. DPX-Survivac will be tested in patients with ovarian cancer. The DPX-Survivac vaccine candidate uses antigens from survivin (in-licensed from Merck KGaA) that are formulated in the DepoVax™ vaccine delivery platform. Survivin is a tumor-associated antigen that is present in cancer cells and generally not expressed in normal cells. Survivin is required by cancer cells to survive, making it a particularly interesting target to test in a cancer vaccine. The DepoVax platform is a patented vaccine delivery formulation that is expected to enhance an immune response targeting cancer cells that contain survivin. The Phase I/II multicenter clinical trial is designed to assess the safety, immunogenicity, and clinical efficacy of the DPX-Survivac vaccine. Patients will be treated with the DPX-Survivac vaccine after completing debulking surgery and chemotherapy treatments. The vaccine will be administered to patients who will also receive an immune-modulating drug to enhance the effect of the vaccine on cancer cells. The Phase I portion of the clinical trial design is an open-label, dose-ranging study to identify the optimal dose of DPX-Survivac to use in the Phase II portion of the study. Immunovaccine expects to start the Phase I study in the fourth quarter of 2011. After a successful Phase I clinical trial, Immunovaccine will be permitted to initiate, without any further application to the FDA, a randomized, double-blinded, placebo-controlled Phase II clinical trial to assess the clinical benefit of DPX-Survivac in patients with advanced ovarian cancer. Source: Marketwire 6/20/11

Positive Results Seen Regarding Erectile Dysfunction in Post-Prostatectomy Study

VIVUS, Inc. in June announced positive results from REVIVE-RP (TA-303), a randomized, double-blind, placebo-controlled, parallel group, multicenter Phase III study of the safety and efficacy of avanafil in the treatment of erectile dysfunction (ED) following bilateral, nerve-sparing, radical prostatectomy (RP) in 298 men with ED. Avanafil met all primary endpoints by demonstrating improvements from baseline in erectile function (EF) as measured by the Sexual Encounter Profile (both SEP 2 and SEP 3) and improvement in the erectile function domain of International Index of Erectile Function (IIEF). The study also indicated a favorable safety profile and successful intercourse (as measured by SEP 3) was observed as early as 15 minutes after dosing, without any restrictions on food or alcohol. Treatment with both doses of avanafil (100 mg and 200 mg) was associated with significant improvements in each of the coprimary endpoints (SEP2, SEP3, and IIEF-EF) compared to placebo; patients treated with 100 mg and 200 mg of avanafil improved their ability to have successful intercourse (SEP 3) four- and five-fold, respectively, from the start of treatment; and treatment with avanafil improved erectile function in a dose-dependent manner with significant increases in the IIEF scores from the beginning of treatment through the end of treatment. On average, subjects entering the study were 58 years old and 19 months past their surgery dates with documented severe ED. Subjects were randomized to 100 mg or 200 mg avanafil or placebo and were instructed to take one dose of study drug 30 minutes prior to initiation of sexual activity. The study had a four-week run-in period followed by 12 weeks of treatment. The avanafil Phase III program consists of TA-301 (REVIVE), TA-302 (REVIVE-Diabetes), and TA-303 (REVIVE-RP). There was also a 52-week, open-label, long-term safety study (TA-314). In the three Phase III studies, all doses of avanafil tested met the primary endpoints, with successful intercourse achieved by some subjects in 15 minutes or less after administration. TA-314 evaluated avanafil for up to 52 weeks in 712 men, 486 with a history of ED and 226 with diabetes and ED, across 40 centers throughout the U.S. Patients completing REVIVE or REVIVE-Diabetes were eligible for rollover into TA-314. The study met all primary endpoints by demonstrating sustained improvement from baseline in erectile function as measured by both SEP 2 and SEP 3 and improvements in the IIEF. The study also indicated a favorable side effect profile and successful intercourse (as measured by SEP 3) in as little as 15 minutes and beyond six hours after dosing, without any restrictions on food or alcohol intake. VIVUS expects to file a New Drug Application with the Food and Drug Administration for avanafil in the second quarter of 2011. Source: PRNewswire 6/17/11

Phase Ib Trial of Treatment for Chronic Complications of Diabetes Initiated

Cebix Inc. announced in June it is advancing the development of modified C-peptide for the treatment of complications of diabetes. The company has initiated a Phase Ib clinical trial to evaluate Ersatta™, its proprietary long-acting form of C-peptide, in patients with type 1 diabetes who, because of their disease, lack this endogenous peptide. Following the successful completion of this study, the company is planning a mid-stage clinical program in diabetic peripheral neuropathy and other chronic conditions associated with diabetes that may be reversed by replacing C-peptide. The primary objectives of the randomized, blinded, placebo-controlled Phase Ib study are to assess the safety, tolerability, and single- and multiple-dose pharmacokinetics of Ersatta after subcutaneous administration. The study is estimated to enroll 30 to 60 patients and will be conducted at up to six sites in the U.S. Cebix has been granted fast track status by the Food and Drug Administration for Ersatta in the diabetic peripheral neuropathy indication. Source: PRNewswire 6/16/11

Phase II Sleep Maintenance Insomnia Study Shows Reduction of Mid-Night Awakenings

Results of a Phase II study sponsored by Somnus Therapeutics, Inc. add further evidence supporting the efficacy and safety of a novel bedtime therapeutic that addresses a major underserved need of insomnia patients: maintaining sleep. SKP-1041, a modified-release formulation of zaleplon, is designed to accomplish this by reducing middle-of-the-night awakenings without interfering with natural sleep onset and early deep sleep. At all three doses tested, SKP-1041 significantly reduced time spent awake during the night compared to placebo, with no evidence of next-morning adverse cognitive effects. In the study, researchers saw statistically significant reductions in the time spent awake during the night for all three dosage strengths tested. For the 15 and 20 mg doses, there was a significant reduction in the number of middle-of-the-night awakenings during hours 3 to 7 of the eight-hour sleep period, as well as increased total sleep time for hours 3 to 7. Using the Digit Symbol Substitution Test and Digit Span Test to test for next-day effects on cognition, researchers saw no impairment compared to placebo at all three doses. The study was conducted in 67 nonelderly adults with primary insomnia characterized by middle-of-the-night awakening, and was a four-way, double-blind, placebo-controlled, double-dummy crossover evaluation conducted in a sleep laboratory setting. Source: Business Wire 6/15/11

Enrollment Begins in U.S. Trial to Evaluate Abdominal Stent-Graft

Bolton Medical announced in June it has begun its Bolton mEdical abdomiNal stEnt graFt trIal with Treovance (B.E.N.E.F.I.T.). The first case was performed on June 9 by Michael C. Stoner, MD, chief of vascular and endovascular surgery at East Carolina University/East Carolina Heart Institute, Greenville, N.C. The second case was performed on June 10 by Edward Woo, MD, vice-chief and associate professor of surgery at the University of Pennsylvania, Philadelphia, Pa. The primary objective of the B.E.N.E.F.I.T. clinical study is to assess the safety and performance of the Treovance abdominal stent-graft in subjects with infrarenal aortic aneurysms. Results of this study will support Food and Drug Administration submissions of the product in the United States. Phase I of the study includes 30 patients enrolled at seven institutions located throughout the U.S. In Europe, the company's ADVANCE study with Treovance has been ongoing since March 2011. Source: Marketwire 6/15/11

Company May Advance Spinal Cord Stem Cell ALS Treatment to Cervical Transplantations

Neuralstem, Inc. has provided an update on the progress of its ongoing Phase I human clinical trial of the company's spinal cord stem cells in the treatment of 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 12 patients, all of whom received injections in the lumbar region of the spine only, the trial's safety monitoring board has unanimously approved advancing the trial to transplantions in the cervical region. The next three patients, all of whom are ambulatory, will each receive five injections, unilaterally, in the cervical spinal cord. In addition to the board's approval, the Food and Drug Administration (FDA) must also approve the trial's moving to the next level of transplantations. The company expects to present the data from the first 12 patients to the FDA in the near future. While still primarily a safety trial, the company hopes that cervical injections can help patients' breathing and swallowing, the areas which most often lead to loss of life in ALS. The trial is the first FDA-approved ALS stem cell trial, and has been under way since January 2010. The trial plans to enroll up to 18 ALS patients, who will be examined at regular intervals postsurgery. All of the first six patients treated in the trial were nonambulatory. Of these, the first three received five injections each, unilaterally, in the lumbar region of the spinal cord. The next three patients received 10 injections each, bilaterally in the lumbar region. All remaining trial patients are ambulatory, and therefore represent earlier stages of disease progression. Of the ambulatory group, the first three patients received five injections each, unilaterally, in the lumbar region. The last three received 10 injections each, bilaterally, in the lumbar region. While the trial is evaluating only the safety of the cells and procedure, it includes exploratory endpoints, including attenuation of motor function loss, maintenance of respiratory capacity, and stabilization of patients along the ALS functional rating scale. Source: EurekAlert! 6/14/11

Surgical Approach Being Optimized for Trial of Neo-Urinary Conduit in Bladder Cancer

Tengion, Inc. in June provided an update on the clinical trial of the company's lead clinical product candidate, the Neo-Urinary Conduit™, for use in bladder cancer patients requiring a urinary diversion following bladder removal (cystectomy). Tengion is continuing to work with investigators to optimize the surgical approach as part of its ongoing clinical trial of the product, and is working closely with clinical investigators, the data safety monitoring board, and the U.S. Food and Drug Administration (FDA) to advance the study. Following a review of clinical data from the trial thus far, a plan has been developed to collect additional clinical data while modifying the surgical approach for future implants. The company expects to submit these data and changes to the FDA in the third quarter of 2011, prior to enrolling additional patients in the trial. The study is designed to provide data on the safety profile and preliminary efficacy for the Neo-Urinary Conduit as an alternative to the current standard treatment requiring the use of a patient's own bowel tissue, which can cause significant complications, as well as to provide investigators with data to optimize the surgical technique and postsurgical patient care during the trial. To date, three patients have been enrolled and implanted in the clinical trial at both the University of Chicago Medical Center and at the Johns Hopkins Hospital in Baltimore, Md. Source: PRNewswire 6/13/11

Final Three-Year Results from HORIZONS-AMI Trial Published

Data from the landmark HORIZONS-AMI clinical trial demonstrated that the administration of the anticoagulant medication bivalirudin enhanced survival compared to the use of heparin plus a glycoprotein (GP) IIb/IIIa inhibitor in heart attack patients undergoing angioplasty after three years. Use of a drug-eluting stent (paclitaxel) was also shown to be more effective than a bare-metal stent, with equivalent safety. Final three-year results of the trial were published in the June 13, 2011, issue of The Lancet. After three years, treatment with bivalirudin alone compared to heparin plus a GP IIb/IIIa inhibitor resulted in significantly reduced rates of all-cause mortality (5.9 percent vs. 7.7 percent), cardiac mortality (2.9 percent vs. 5.1 percent), reinfarction (6.2 percent vs. 8.2 percent) and major bleeding not related to bypass graft surgery (6.9 percent vs. 10.5 percent). There were no significant differences in the incidence of ischemia-driven target vessel revascularization, stent thrombosis, stroke, or composite adverse events. In addition, at three years, the implantation of a paclitaxel-eluting stent compared to a bare-metal stent resulted in significantly lower rates of ischemia-driven target lesion revascularization (9.4 percent vs. 15.1 percent) with no significant differences in the rates of death, reinfarction, stroke, or stent thrombosis. The reported reduction in all-cause mortality seen in the trial equates to 18 lives saved per 1,000 patients treated with bivalirudin. Patients who received a paclitaxel-eluting stent had a 40 percent reduction in risk of ischemia-driven target lesion revascularization after three years compared to those patients given a bare-metal stent. This is the largest study to focus on the appropriate use of anticoagulation medications and drug-eluting stents in patients experiencing the most dangerous form of heart attack (ST-elevation myocardial infarction). Sponsored by the Cardiovascular Research Foundation, with research grant support from Boston Scientific Corp. and the Medicines Company, HORIZONS-AMI enrolled 3,602 patients presenting with a heart attack to hospitals in 11 countries. More than 120 national and international interventional cardiology centers participated in the trial. Source: EurekAlert! 6/13/11

Potential CF Therapies Show Promising Results in Phase II

Vertex Pharmaceuticals Inc. and the Cystic Fibrosis Foundation in June announced promising results from an ongoing Phase II study evaluating combinations of VX-770 and VX-809, potential medicines designed to treat the defective protein that causes cystic fibrosis (CF). The study enrolled 62 people with two copies of the most common CF mutation, known as Delta F508. The trial lasted three weeks. Participants took VX-809 for two weeks, and VX-809 and VX-770 together for a third week. Patients who took the drug regimen showed a positive change in sweat chloride levels. Excessive sweat chloride is a key clinical indicator of cystic fibrosis. The findings suggest that VX-809 and VX-770 together improve function of the defective CF protein, known as CFTR. “The results of this study represent a milestone in our efforts to expand the use of small molecules to attack the root cause of cystic fibrosis in those with the most common defect,” said Robert J. Beall, PhD, president and CEO of the CF Foundation. “These data, while early, provide important new information that validates our approach and supports continued study of a combination-therapy approach to treating the basic defect of cystic fibrosis.” The CF Foundation worked with Vertex to discover VX-770 and VX-809, and has provided substantial scientific, financial, and clinical support throughout the development process, including an approximately $75 million investment. Vertex plans to initiate the second part of the study in the fourth quarter of 2011. In people with the Delta F508 mutation, the defective protein does not move to its proper place at the cell surface. VX-809 is designed to help the protein reach the cell surface, while VX-770 aims to help the protein function more normally once it is at the cell surface. Source: Cystic Fibrosis Foundation 6/9/11

Oral Vaccine Clinical Trial Under Way for Avian Influenza

Vaxart, Inc. has begun dosing volunteers in a Phase I clinical trial. This is the first clinical study evaluating a vaccine that uses the company's novel oral-vaccine platform technology. The trial site is in the United States. "This first trial in humans is important, because if safety is demonstrated with one vaccine, we can expect that later vaccines using the same Vaxart technology will also be safe," said Vaxart founder and CSO Sean Tucker, PhD. Vaxart's first oral vaccine candidate is designed to protect against H5N1 avian influenza. The company also has a pipeline of additional vaccines in development, all based on its oral-delivery technology. Vaxart also announced the issuance of U.S. patent no. 7,879,602, which provides broad protection for the company's oral-delivery technology. Central to the company's approach is the incorporation of a unique adjuvant, the vaccine component that enhances immune responses, in the vector that delivers the vaccine antigen. Vaxart's adjuvant works by binding to Toll-Like Receptor 3 to stimulate a potent immune response when the vaccine is taken orally. Vaxart's technology also enables all of the company's vaccines to use the same vector, or delivery vehicle. Source: PRNewswire 6/7/11

Clinical Trial to Tackle Hearing Loss from Personal Music Players

Sound Pharmaceuticals will begin recruiting subjects for a new clinical trial testing the oral drug SPI-1005 to prevent the hearing loss induced by loud music. Exposure to loud music or noise can induce temporary and permanent auditory threshold shifts (TTS or PTS). In the trial, young adults will listen to music that has been recorded onto personal music players. Volunteers will take either a placebo or SPI-1005 starting two days before and then listen to the player for four hours to induce a mild TTS. SPI-1005 is an oral capsule that contains a proprietary formulation of ebselen, a small molecule that mimics the activity of glutathione peroxidase, a critical enzyme in the inner ear that protects it from loud sounds. After noise exposure, the activity of the enzyme decreases in several inner ear structures, including the auditory hair cells. In several preclinical studies, ebselen treatment was shown to improve the function of auditory hair cells and reduce the TTS induced by intense noise exposure. Currently, there are no drugs for the prevention and treatment of sensorineural hearing loss approved by the Food and Drug Administration. Source: PRNewswire 6/6/11

Stem Cell Bandage Receives Approval for Study

Millions of people with knee injuries could benefit from a new type of stem cell bandage treatment if clinical trials are successful. The world's first clinical trial for the treatment of patients with torn meniscal cartilage has received approval from the U.K. regulatory agency, the MHRA, to commence. The current treatment for the majority of tears is the removal of the meniscus, a procedure that often results in the early onset of osteoarthritis. The Phase I trial, one of the first in the U.K. to be approved using stem cells, will treat meniscal tear patients with a cell bandage product, seeded with the patient's own, expanded, stem cells. The cell bandage, produced by Azellon Ltd, a University of Bristol spin-out company, is focused on the research, development, and commercialization of an adult autologous (patient's own) stem cell technology, which in vitro (tissue culture) has shown great promise for the healing of meniscal tears. The trial is designed primarily to test the safety profile of Azellon's cell bandage in 10 meniscal tear patients, but some information on whether or not it works will also be obtained. The bandage will be implanted in a simple surgical procedure using a specially designed instrument that helps to deliver the cells into the injured site as a first-line treatment in place of removal of the meniscus. Patients will be closely monitored for safety over a five-year follow-up period. Source: EurekAlert! 6/3/11

Company Announces Completion of Enrollment for IDE Trial

IDEV Technologies, Inc. in June announced the completion of enrollment in the SUPERB Trial, a Food and Drug Administration-approved investigational device exemption (IDE) trial evaluating the use of IDEV's Supera® stent system for treatment of peripheral artery disease in the superficial femoral artery (SFA). Enrollment was completed in May, making SUPERB one of the fastest enrolling SFA trials. The trial is a prospective, single-arm study of 258 patients at 49 U.S. sites, led by national coinvestigators Kenneth Rosenfield, MD, of Massachusetts General Hospital in Boston, and Lawrence Garcia, MD, of Steward's St. Elizabeth's Medical Center of Boston. The study's objective is to demonstrate the safety and effectiveness of the stent. The SUPERB trial results will be used to support IDEV's premarket approval submission for an additional peripheral vascular indication. Source: PRNewswire 6/2/11

Phase Ib Study Initiated for Anti-Inflammatory Agent

Ampio Pharmaceuticals, Inc. announced in late May that it received ethics board approval for a Phase Ib clinical trial in Australia of its biologic anti-inflammatory agent, Ampion™. Patients are now being recruited for first dosing in the three-arm, placebo-controlled, 60-patient trial designed to demonstrate efficacy in the treatment of osteoarthritis of the knee as well as to confirm patient safety and tolerance. The present "standard of care" treatment for this condition is the injection of a short acting local anesthetic agent combined with a long acting steroid into and around the joint. In the Ampion trial, the mitigation of pain and loss of function caused by osteoarthritis will be assessed at intervals from the time of injection. Patients will be evaluated for 72 hours and various parameters will be followed with the goal of demonstrating that Ampion is well tolerated and provides pain relief through decreased inflammation as well as improves the range of motion of the knee. The test molecule is produced in the body from serum albumin as an integral part of the innate control of inflammation. The company expects the trial results will form the basis for submissions to various regulatory agencies to conduct Phase II/III studies of the active component in numerous inflammatory conditions. Source: PRNewswire 5/31/11

NIH Stops Clinical Trial on Combination Cholesterol Treatment

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) has stopped a clinical trial studying a blood lipid treatment 18 months earlier than planned. The trial found that adding high dose, extended-release niacin to statin treatment in people with heart and vascular disease did not reduce the risk of cardiovascular events, including heart attacks and stroke. Participants were selected for AIM-HIGH because they were at risk for cardiovascular events despite well-controlled low-density lipoprotein (LDL or bad cholesterol). Their increased risk was due to a history of cardiovascular disease and a combination of low high-density lipoprotein (HDL or good cholesterol) and high triglycerides, another form of fat in the blood. Low HDL and elevated triglycerides are associated with an increased risk of cardiovascular events. While lowering LDL decreases the risk of cardiovascular events, it has not been shown that raising HDL similarly reduces the risk of cardiovascular events. During the study's 32 months of follow-up, participants who took high dose, extended-release niacin and statin treatment had increased HDL cholesterol and lowered triglyceride levels compared to participants who took a statin alone. However, the combination treatment did not reduce fatal or nonfatal heart attacks, strokes, hospitalizations for acute coronary syndrome, or revascularization procedures to improve blood flow in the arteries of the heart and brain. "Seeking new and improved ways to manage cholesterol levels is vital in the battle against cardiovascular disease," said Susan B. Shurin, MD, acting director of the NHLBI. "This study sought to confirm earlier and smaller studies. Although we did not see the expected clinical benefit, we have answered an important scientific question about treatment for cardiovascular disease. We thank the research volunteers whose participation is key in advancing our knowledge in this critical public health area, and the dedicated investigators who conducted the study." The NHLBI funded the AIM-HIGH study with additional support from Abbott Laboratories. Abbott also provided Niaspan and Merck Pharmaceuticals provided Zocor. All drugs used in the study were approved for marketing in the United States and Canada and have been on the market for many years. Researchers began recruiting participants in early 2006. The study was scheduled to finish in 2012. However, an independent data and safety monitoring board on April 25 concluded that high-dose, extended-release niacin offered no benefits beyond statin therapy alone in reducing cardiovascular-related complications in this trial. The rate of clinical events was the same in both treatment groups, and there was no evidence that this would change by continuing the trial. The board also noted a small and unexplained increase in ischemic stroke rates in the high-dose, extended-release niacin group. This contributed to the NHLBI acting director's decision to stop the trial before its planned conclusion. Previous studies do not suggest that stroke is a potential complication of niacin, and it remains unclear whether this trend in AIM-HIGH arose by chance, was related to niacin administration, or some other issue. All AIM-HIGH study participants have been informed of the results and will be scheduled for clinic visits within the next 2.5 months. Participants will be followed for an additional 12 to 18 months. Source: EurekAlert! 5/26/11

International Trial Finds Polypill Halves Predicted Heart Disease and Stroke Risk

The world's first international polypill trial has shown that a four-in-one combination pill can halve the predicted risk of heart disease and stroke. The results were published online in late May in the open access journal PLoS One. The once-a-day polypill contains aspirin and agents to lower blood pressure and cholesterol. These drugs are currently prescribed separately to millions of patients and are known individually to cut the risk of disease, but many experts believe that combining them into a single pill will encourage people to take the medications more reliably. The trial tested the effectiveness and tolerability of the polypill in 378 people with raised risk of cardiovascular disease, who did not necessarily have high blood pressure or cholesterol, against a placebo. The participants came from the U.K., Australia, Brazil, India, New Zealand, The Netherlands, and the U.S., with core funding for the central coordination of the trial provided by the Wellcome Trust. "The results show a halving in heart disease and stroke can be expected for people taking this polypill long-term," said Prof. Anthony Rodgers of the George Institute for Global Health, who led the international consortium. National trials of similar combination polypill treatments have previously been conducted in India, Iran, and Sri Lanka, but this is the first trial to combine data from patients at international centers, and the first to look reliably at the incidence of side effects against a placebo. This polypill will be available in India soon and then elsewhere within a few years, according to regulatory timelines within each individual country. Additional funding for the trial was provided by the British Heart Foundation, the Health Research Council of New Zealand, the National Heart Foundation of New Zealand, the National Health and Medical Research Council of Australia and the Brazilian Ministry of Health. Source: EurekAlert! 5/25/11

Finances Raised to Advance Drug Into Phase III Osteoporosis Study

Radius Health, Inc. in May announced that the company has raised approximately $91 million in its third financing round and will use the proceeds primarily to fund Phase III clinical development of the subcutaneous injection form of BA058, the company's novel, proprietary PTHrP (parathyroid hormone-related protein) analog, for the treatment of osteoporosis. Data from the study are intended to form the primary basis for an efficacy claim to support applications for marketing authorization of BA058 Injection in the United States and Europe. In connection with the financing, Radius completed a services agreement with Nordic Bioscience, whereby Nordic will manage the pivotal trial of BA058. The 18-month study will enroll 2,400 patients and will be conducted in eight countries at 11 centers operated by the Center for Clinical and Basic Research, a clinical research organization. BA058 is in development by Radius in both subcutaneous injection and transdermal delivery forms as a treatment for osteoporosis. In Phase I and II studies, injected BA058 has demonstrated the potential to widen the anabolic window for osteoporosis therapy by stimulating bone formation with limited effect on bone resorption and greatly reduced risk of hypercalcemia. In the Phase II study, BA058 achieved greater and faster gains in bone mineral density at critical fracture sites compared to Forteo®, with a lower incidence of hypercalcemia. The BA058 Microneedle Patch—the transdermal form of BA058 under development by Radius in collaboration with 3M Drug Delivery Systems—is currently undergoing Phase I clinical trials. Radius acquired exclusive worldwide rights (excluding Japan) to develop, manufacture, and distribute BA058 and its analogs from Ipsen in 2005. Source: PRNewswire 5/24/11

Gel Demonstrates Efficacy in Bacterial Vaginosis

Starpharma Holdings Limited in May announced successful results of a major Phase II clinical study that demonstrated efficacy of VivaGel® for the treatment of bacterial vaginosis (BV). The study showed that treatment with VivaGel (containing 1 percent of the active, SPL7013), once daily for seven days, resulted in 74 percent of patients achieving clinical cure of BV two to five days after completion of therapy, compared to just 22 percent in the placebo group. Moreover, two to three weeks after completion of therapy, 46 percent of patients achieved clinical cure of BV, compared to just 12 percent for the placebo, indicating that the product provided lasting cure in a significant proportion of the women. Both results were highly statistically significant and cure at both time points is considered by clinicians to be important in the clinical management of BV. In Starpharma's study, vaginal BV discharge as assessed by the investigator was cured following treatment in 89 percent of the VivaGel-treated patients. Unpleasant vaginal odor was cured in 78 percent of the VivaGel-treated patients. According to the company, the product is not absorbed (and so is free from systemic effects), can be used with condoms, and has the potential to be used for prolonged periods to prevent recurrence of BV. The study was a double-blind, randomized, placebo-controlled, dose-ranging trial and was conducted at sites in the U.S. under an Investigational New Drug application with the Food and Drug Administration. The study enrolled 132 women who were randomized to receive VivaGel (0.5 percent, 1 percent or 3 percent SPL7013) or placebo. The incidence of adverse events, including genitourinary adverse events, was similar across all placebo gel and VivaGel groups. No severe (grade 3) adverse events were observed in the VivaGel groups. Two severe adverse events were observed in the placebo. Based on the results of this study, Starpharma will undertake further discussions with regulatory authorities, with a view to initiating Phase III registration trials of VivaGel for the treatment of BV in late 2011 or early 2012. As previously announced, Starpharma is also well advanced in its planning of studies to determine the efficacy of VivaGel for prevention of BV recurrence, and expects to commence this trial in the third quarter of 2011. Source: PRNewswire 5/23/11

Stent Demonstrates Safety and Effectiveness in Small Vessel Study

Boston Scientific Corp. in May announced 12-month results from its PLATINUM Small Vessel study, demonstrating safety and effectiveness outcomes for the 2.25 mm PROMUS Element™ everolimus-eluting platinum chromium stent system in treating small vessel coronary disease. The study is a global, prospective, single-arm subtrial of the PLATINUM clinical program. It compares the PROMUS Element stent (2.25 mm) in 94 patients with small vessels (greater than or equal to 2.25 to less than 2.50 mm reference vessel diameter and less than or equal to 28 mm lesion length) to a prespecified performance goal based on results from patients treated with the TAXUS® Express® paclitaxel-eluting stent. Analysis of the data was presented at the annual EuroPCR Scientific Program in Paris. According to the presentation, the PLATINUM Small Vessel data demonstrate "exceptionally low rates of revascularization, while reporting no myocardial infarction or stent thrombosis at one year in patients treated with the 2.25 mm PROMUS Element stent." The study met its primary endpoint of target lesion failure (TLF) at 12 months with a rate of 2.4 percent for the 2.25 mm PROMUS Element stent in the per protocol population compared to a prespecified performance goal of 21.1 percent based on historical outcomes for the 2.25 mm TAXUS Express stent. Components of TLF in the per protocol population included cardiac death related to the target vessel (2.4 percent), myocardial infarction related to the target vessel (MI, 0.0 percent), and ischemia-driven target lesion revascularization (TLR, 0.0 percent). Clinical outcome rates at 12 months in the intent-to-treat population were also low for cardiac death (3.3 percent), MI (0.0 percent), TLR (2.2 percent), and ARC definite/probable stent thrombosis (0.0 percent). The PLATINUM clinical program is evaluating the safety and effectiveness of the PROMUS Element stent in five multicenter studies totaling more than 1,800 patients, including a global, randomized, pivotal controlled trial in workhorse lesions, and single-arm studies evaluating small vessels, long lesions, pharmacokinetics, and quantitative coronary angiography and intravascular ultrasound data. In the U.S., the stent is an investigational device, limited by applicable law to investigational use and not available for sale. Source: PRNewswire 5/20/11

Phase I/II Results Published for Stem Cell Therapy for Critical Limb Ischemia

Aldagen, Inc. in May announced that results from the Phase I/II clinical trial of ALD-301 were published in Catheterization and Cardiovascular Interventions. ALD-301 is a stem cell therapy being developed as a treatment for critical limb ischemia (CLI), the most advanced form of peripheral arterial disease (PAD). The study was a multicenter trial and included Cardiology PC, Duke University, Texas Heart Institute, and St. Joseph's Research Institute. Dr. Emerson Perin from the Texas Heart Institute is the lead author on the publication. The double-blind study included a total of 21 subjects who were randomly selected to receive an injection of either ALD-301 or unsorted cells from their own bone marrow (autologous bone marrow mononuclear cells). The primary objective of the trial was to evaluate the safety of ALD-301. Secondary endpoints of the trial included change in clinical status from baseline to 12 weeks, as measured by the Rutherford scale, a well-accepted clinical categorization of the extent of CLI. In addition, change in blood flow to the leg was measured by two well-accepted clinical tools for assessing the extent of CLI, the ankle-brachial index (ABI), and transcutaneous partial pressure of oxygen. As detailed in the publication, ALD-301 was shown to be well tolerated, with no therapy-related serious adverse events. Patients treated with ALD-301 showed significant improvements in three efficacy endpoints: Rutherford category, ABI, and quality of life, compared to baseline at 12 weeks. Additionally, patients treated with ALD-301 showed a significant decrease in rest pain compared to baseline at six weeks. The company plans to initiate a 150-patient Phase II trial as the next step in the development of ALD-301, which is the population of ALDH(br) stem cells produced using Aldagen's proprietary technology to sort a specified quantity of bone marrow collected from the patient receiving the therapy. These adult stem cells express high levels of the enzyme ALDH, which plays an important role in controlling the developmental state of stem and progenitor cells. ALD-301 is injected into the patient's leg muscle. Preclinical research suggests that ALDH(br) cells derived from bone marrow may promote the repair of ischemic tissue damage. Source: Marketwire 5/19/11

Promising Interim Survival Data Reported From Phase II Recurrent GBM Trial

Peregrine Pharmaceuticals, Inc. in May announced interim median overall survival of 8.8 months (38 weeks, 40 patients at first relapse) from a Phase II trial for Cotara® in recurrent glioblastoma multiforme (GBM) brain cancer. Additional data from this trial will be presented in a poster, which was selected for an oral poster discussion, at the Annual Meeting of the American Society of Clinical Oncology in Chicago, Ill., on June 3. Cotara is a targeted monoclonal antibody linked to a radioisotope that is administered as a single-infusion therapy directly into the tumor, destroying the tumor from the inside out, with minimal exposure to healthy tissue. Typical patient prognosis in GBM is approximately six months at first relapse. Dr. Vladimir Evilevitch, a nuclear medicine and oncology specialist, has joined Peregrine to help advance the novel radiopharmaceutical therapy. The last patients in the Phase II trial completed treatment in December 2010. Source: Marketwire 5/19/11

Phase II Study in Treatment-Resistant Depression Voluntarily Terminated

Evotec AG and Roche in May decided to voluntarily terminate the first proof-of-concept study in treatment-resistant depression with their NR2B subtype selective NMDA antagonist EVT 101. The decision to terminate the Phase II study was triggered by difficulties to recruit patients under the current study protocol, resulting in the possibility of inconclusive results. EVT101 was generally well tolerated in healthy volunteers and patients enrolled so far. Difficulties in conducting the study in treatment-resistant depression, the need to sharpen the toxicology profile, and a potential requirement for an altered dosage scheme lead to an overall delay in the program. Based on this, the parties concluded to terminate the clinical development. This clinical development has been the key part of an alliance between Evotec and Roche, in which Roche has provided all funding in exchange for certain option rights after a proof-of-concept result with NR2B subtype selective NMDA antagonist in treatment-resistant depression. Evotec retains all rights in the EVT100 series, especially the back-up compound EVT103, and will enter into partnering discussions for these assets in another clinical development partnership. As advanced clinical development of drug candidates is not part of Evotec's core business, Evotec does not intend to pursue further clinical development of its NR2B subtype selective NMDA antagonist without a partner. Source: Globe Newswire 5/18/11

Trial of Shiga Toxin-Producing E. Coli Treatment Proceeds to High-Dose Cohort

Thallion Pharmaceuticals Inc. in May announced that the independent data monitoring committee for the company's randomized, double-blind, placebo-controlled Phase II SHIGATEC trial has completed a planned safety analysis and recommends that the trial continue as per the protocol. This scheduled review occurred after the treatment and 56-day follow-up of the 22 patients that received the low-dose treatment (1 mg/kg/dose) in the first cohort of the trial. The study is evaluating Shigamabs® as a treatment for Shiga toxin-producing E. coli (STEC) infection. Thallion has advised its clinical sites to initiate enrollment of the second, high-dose cohort of the trial in which patients will receive 3 mg/kg/dose. The company anticipates the completion of patient enrollment and the top-line results to be available prior to the end of the year. The final 21 patients in the trial will be enrolled at the company's clinical sites in South America. The primary endpoints for the trial are safety and tolerability. Secondary endpoints include pharmacokinetics and objective measures of efficacy using single and composite endpoints. Source: Marketwire 5/16/11

Company Raises Funds to Advance Urology Program Into Clinical Trials

Trillium Therapeutics Inc. announced in May that it has raised $1 million from a new undisclosed investor. The funds will be used to advance its lead program, TTI-1612, into clinical trials for the treatment of interstitial cystitis, also known as bladder pain syndrome. The first trial is projected to start in the second half of this year. Interstitial cystitis is a chronic, debilitating, and poorly treated bladder disease affecting millions of women in the U.S. alone. It is believed to develop as a result of dysfunction in the protective epithelial layer lining the bladder. TTI-1612, a locally delivered recombinant growth factor, is being developed to correct this dysfunction and restore the bladder epithelium to a normal, healthy state. Trillium is in the final stages of completing the preclinical toxicology studies required for testing in humans, and plans to submit a clinical trial application later this year. The company intends to secure additional financing and/or a development partner prior to the start of randomized Phase II studies in 2012. Source: PRNewswire 5/12/11

Tourette Syndrome Association and Firm Collaborate on Trial for Treatment

The national Tourette Syndrome Association (TSA) and Psyadon Pharmaceuticals Inc. have announced their collaboration on a clinical trial to determine the potential efficacy of a novel drug, ecopipam, for managing the symptoms of the neurological disorder Tourette syndrome. "This is the first time in our 39-year history that TSA has collaborated with the pharmaceutical industry and helped to fund a clinical drug trial for the potential treatment of [the syndrome]," said Judit Ungar, president of the New York-based not-for-profit organization. The TSA will also assist with subject recruitment for the clinical trial of ecopipam, the rights to which are owned by Psyadon. The Food and Drug Administration granted ecopipam an orphan drug designation for the treatment of the syndrome in 2010. It belongs to a class of agents referred to as dopamine D1 antagonists, and interacts with nerve cells and systems in the brain that are thought to contribute to the development of tics and other symptoms in the syndrome. The clinical trial, which has already begun, is a Phase IIa, open-label, nonrandomized trial to examine the ability of ecopipam to both reduce tic severity and also to determine its safety in individuals (18 to 65 years of age) with the syndrome. The study is being conducted at four sites across the U.S. and is expected to last for several months. Data from this clinical trial are expected to be released by mid-2012. Source: PRNewswire 5/11/11

Independent Investigators Conducting Phase I Study of Insulin Formulations

Biodel Inc. announced in May that independent investigators are conducting a pump trial of Biodel's two ultra-rapid-acting formulations of recombinant human insulin. The formulations, BIOD-105 and BIOD-107, are designed to result in more rapid insulin action compared to currently marketed mealtime insulin analogs. This study is designed as a double-blind, three-period, crossover trial in which insulin pumps will be used to deliver BIOD-105, BIOD-107, and Humalog® each at separate dosing visits in approximately eight patients with type 1 diabetes. The study is expected to be completed in the fourth calendar quarter of 2011, and will evaluate pharmacokinetic, pharmacodynamic, and injection site tolerability profiles of BIOD-105 and BIOD-107 relative to that of Humalog®. Drs. W. Kenneth Ward and Jessica Castle of the Division of Endocrinology, Diabetes, and Clinical Nutrition at Oregon Health and Sciences University will serve as principal investigators for this trial. Currently available prandial insulins are used in pumps, but often are not absorbed rapidly enough to achieve optimal mealtime glucose control. It is believed that an ultra-rapid-acting insulin will be better suited for pump therapy than currently marketed mealtime insulin analogs. "In the third week of March, we initiated a study of similar design to Dr. Ward's study, in which BIOD-105, BIOD-107, and Humalog® are delivered by standard injection," said Dr. Alan Krasner, chief medical officer of Biodel. "The results of both studies will help choose the best candidate for further development. We look forward to receiving these data." Source: PRNewswire 5/10/11

Phase IIb Data are Encouraging for Patients With Moderate to Severe Crohn's Disease

New study findings showed that treatment with Stelara® (ustekinumab) induced and maintained clinical response in patients with moderate to severe Crohn's disease who had previously failed or were intolerant to at least one tumor necrosis factor (TNF) antagonist. Investigators presented findings from a Phase IIb study at Digestive Disease Week, which showed nearly 40 percent of patients receiving Stelara 6 mg/kg achieved clinical response, defined as a 100-point reduction in the Crohn's Disease Activity Index, at week 6, the primary endpoint of the study. Additionally, a significantly greater proportion of week 6 responders to Stelara continuing treatment through week 22 were in clinical response and in clinical remission, compared to the group treated with placebo. While TNF blockers have advanced the treatment of Crohn's disease, for patients who do not respond or lose response, treatment options are limited. In the study, patients received one of three intravenous doses of Stelara or placebo at week 0. At week 6, 36.6 percent, 34.1 percent, and 39.7 percent of patients receiving Stelara 1 mg/kg, 3 mg/kg, or 6 mg/kg, respectively, achieved clinical response, compared to 23.5 percent of patients receiving placebo. The difference in clinical remission was not statistically significant at week 6, a secondary endpoint, with any of the doses tested compared to placebo. In the maintenance phase of the study, individuals classified as responders to Stelara at week 6 were re-randomized to receive subcutaneous Stelara 90 mg or placebo at weeks 8 and 16. At week 22, 69.4 percent of patients maintained clinical response with continued Stelara treatment, compared to 42.5 percent of patients receiving placebo. Clinical remission was seen in 41.7 percent of initial Stelara responders who continued with therapy, compared to 27.4 percent of responders re-randomized to receive placebo. The multicenter, randomized, double-blind, placebo-controlled, parallel-group study included 526 patients with moderately to severely active Crohn's disease. Source: PRNewswire 5/9/11

Positive Results Presented from Largest Shift Work Disorder Trial Ever Conducted

At the Society of General Internal Medicine’s 34th Annual Meeting in Phoenix, Ariz., in April, Cephalon, Inc. presented positive results from a Phase IV trial of nearly 400 people with excessive sleepiness associated with shift work disorder. In the trial, Nuvigil® (armodafinil) tablets improved shift workers’ overall clinical condition late in their shifts (i.e., 4 a.m. to 8 a.m.), including the commute home, compared to placebo. The key secondary endpoint of the study was to assess global function, as measured by the Global Assessment of Functioning (GAF), and patients taking Nuvigil experienced a greater improvement in GAF score compared to those patients taking placebo. Shift work disorder occurs when the body's internal sleep-wake clock is out of sync with the individual’s work schedule--their bodies tell them to go to sleep when their work schedule needs them to stay awake. The primary symptoms of shift work disorder are excessive sleepiness and insomnia. This six-week, double-blind, placebo-controlled study of 383 patients with excessive sleepiness associated with shift work disorder was conducted at 45 sites across the United States. Participants in the study spanned a wide range of occupations associated with shifts or nontraditional work hours, including transportation and material moving, healthcare support, protective services, management roles, and office and administrative support. For the primary endpoint, physicians used the Clinical Global Impression of Change (CGI-C) scale to evaluate the change from baseline (beginning of the study) in overall clinical condition late in the shift. The observation period also included the participant’s commute home from work. Using the CGI-C rating, at the final visit, 77 percent of patients taking the recommended Nuvigil dose of 150 mg (n=177) improved, compared to 57 percent of patients taking placebo (n=182)--a significantly greater improvement. Scores above 70 on the GAF may be considered within the normal range of functioning. This study was the first to use the GAF to provide an assessment of functioning in patients with excessive sleepiness associated with shift work disorder. In this trial, physicians used the GAF to measure a patient’s overall level of functioning at baseline and at the final visit. At baseline, patients in both the placebo and Nuvigil groups were rated an average score of 63, which is indicative of functional impairment associated with shift work disorder. Patients treated with Nuvigil experienced a 9.5 point improvement over baseline in the GAF, to mean scores of 72.6 at the final visit, compared to a 5.2 point improvement to means scores of 67.9 in those taking placebo at final visit. Source: PRNewswire 5/6/11

Studies of RNA-Based Therapies for Ebola and Marburg Viruses Initiated

AVI BioPharma, Inc. in May announced that it initiated dosing in two Phase I clinical studies for AVI-6002 and AVI-6003, its lead drug candidates being evaluated for the treatment of Ebola virus and Marburg virus, respectively. AVI is developing AVI-6002 and AVI-6003 under a competitively awarded contract for up to $291 million from the U.S. Department of Defense through the Joint Project Manager Transformational Medical Technologies program. Both candidates utilize AVI's advanced and proprietary PMOplus™ chemistry. Each study will be randomized, double-blind, and placebo-controlled and involve single escalating doses to assess the safety, tolerability, and pharmacokinetics of each drug candidate in healthy adult volunteers. In each study, five volunteers will be enrolled in one of six cohorts for a total of up to 30 volunteers. The cohorts will include four volunteers who receive the therapeutic, and one who will receive a placebo. Preclinical studies of AVI-6002 and AVI-6003 have been a collaborative effort between AVI and scientists at the U.S. Army Medical Research Institute of Infectious Diseases. Source: Marketwire 5/4/11

First Patient Dosed in Phase I Heart Failure Study

Nile Therapeutics, Inc. in May announced dosing of the first patient in a Phase I clinical trial investigating the use of subcutaneous cenderitide. The trial is being conducted pursuant to Nile's previously announced collaboration with Medtronic and is the first clinical step toward developing cenderitide as a treatment for the post-acute heart failure space, a strategy which was recently granted Fast Track status by the United States Food and Drug Administration. The trial is a placebo-controlled study designed to evaluate pharmacokinetic and pharmacodynamic actions of cenderitide when administered to chronic heart failure patients as a subcutaneous infusion or as a subcutaneous bolus injection. In the first part of the trial, patients will receive two subcutaneous bolus injections of cenderitide. In the second part of the trial, patients will receive either a 24-hour continuous infusion of cenderitide or placebo, delivered through Medtronic's subcutaneous pump technology. The primary purpose of the trial is to understand the doses required to achieve predetermined plasma levels of cenderitide delivered through a subcutaneous infusion pump and the pharmacodynamic activity at these doses. Source: PRNewswire 5/3/11

Phase IIb Trial of Next-Generation Head Lice Treatment Begins

Venture-backed Australian pharmaceutical company Hatchtech Pty Ltd has enrolled the first subjects for its Phase IIb clinical study to confirm the efficacy of its novel head lice treatment DeOvo™. This trial will evaluate the efficacy, safety, and tolerability of two dose levels of a single application of DeOvo compared to vehicle. It will conducted in approximately 132 healthy subjects with head lice infestation, 2 years of age and older in two study centers in the United States. Hatchtech's proprietary agent DeOvo is a topical formulation of a known metalloprotease inhibitor that targets certain proteases that are key to biological processes involved in insect hatch and survival. The trial is expected to be completed by the end of 2011. Source: PRNewswire 5/2/11

Device Study Aims to Reduce Re-Excisions for Lumpectomies

Dune Medical Devices, Inc. in late April announced that the landmark 664-patient pivotal trial evaluating the MarginProbe™ System met its primary endpoints. The MarginProbe System provides surgeons with a real-time, intraoperative technology to detect microscopically positive margins on excised tissues. Top-line data from the study were presented at the 12th Annual Meeting of the American Society of Breast Surgeons in Washington, D.C. Results showed that, when using MarginProbe in addition to standard of care techniques, there was greater than a three-fold increase in surgeons' ability to identify and immediately resect all positive lumpectomy margins, compared to standard of care techniques alone. This improvement led to a 57 percent reduction in patients who were candidates for re-excision (additional surgery) due to positive margins left unresected on the lumpectomy specimen. Patients participating in the international, multicenter, controlled trial underwent lumpectomy surgery and were randomized in the operating room to receive either the standard of care (control group), or the standard of care plus MarginProbe (device group). In the device group, MarginProbe was used to measure each margin of the excised lumpectomy specimen. If the device registered a positive reading, additional tissue was immediately resected from the adjacent breast cavity surface. A primary endpoint of the study was Complete Surgical Resection (CSR), which measured the surgeons' ability to identify and resect all positive margins when present. Roughly 50 percent of patients had one or more positive margins on the lumpectomy specimen (later determined by pathology), and CSR was successful when all margins were identified and completely resected. For the device group, the rate of successful CSR was 72 percent, compared to 22 percent in the control group. Patients who did not achieve successful CSR were considered candidates for re-excision procedures--42 in the device group compared to 98 in the control group (57 percent reduction). Of these candidates, 30 patients in the device group and 62 patients in the control group had a re-excision. In total, 664 women aged 18 years and older, histologically diagnosed with carcinoma of the breast, with nonpalpable malignant lesions requiring image guided localization, and undergoing lumpectomy surgery at one of 21 sites in the U.S. and Israel, were enrolled in the study. Of these women, 596 were randomized in the operating room to one of two evenly distributed groups, either device or control. The MarginProbe System is commercially available in Europe. It is an investigational device in the United States. Source: EurekAlert! 4/29/11

First Patient Enrolled in Traumatic Brain Injury Trial

Stem Cell Therapeutics Corp. in April announced the enrollment of the first patient in an open-label Phase IIa traumatic brain injury (TBI) trial being supported by the company. The principal investigator for this investigator-led clinical trial is Dr. David Zygun at the Foothills Hospital. The purpose of this trial is to characterize the safety profile of NTx®-428, a product based on human chorionic gonadotrophin and epoeitin alpha, when administered to patients who have sustained a TBI. Additionally, a number of secondary endpoints will be studied, including preliminary characterization of magnetic resonance imaging, motor, cognitive, and functional recovery. The trial is anticipated to complete the enrollment of 10 patients by the end of 2011. Source: Marketwire 4/28/11

NIH Study Finds Two Treatments Equally Effective Against AMD

Researchers are reporting results from the first year of a two-year clinical trial showing that Avastin, a drug approved to treat some cancers and that is commonly used off-label to treat age-related macular degeneration (AMD), is as effective as the Food and Drug Administration (FDA)-approved drug Lucentis for the treatment of AMD. The report, from the Comparison of AMD Treatments Trials (CATT), was published online in the New England Journal of Medicine on May 1. CATT is funded by the National Eye Institute, a part of the National Institutes of Health (NIH). Genentech, the maker of both drugs, originally developed Avastin to prevent blood vessel growth that enables cancerous tumors to develop and spread. In 2004, the FDA approved Avastin for the systemic treatment of metastatic colon cancer. Genentech later developed Lucentis, derived from a protein similar to Avastin, specifically for injection in the eye to block blood vessel growth in AMD. In 2005, two Genentech-sponsored clinical trials established Lucentis as highly effective for the treatment of wet AMD. During the year between the announcement of the trial results and the release of Lucentis, ophthalmologists began injecting AMD patients with low doses of Avastin, due to its similarity to Lucentis and its availability. The FDA has not licensed Avastin for the treatment of AMD. Numerous physicians noted a beneficial treatment effect and Avastin's use grew rapidly despite the lack of data on safety, efficacy, and dosing from randomized clinical trials to support its use. Ophthalmologists used Avastin primarily as needed, or pro re nata (PRN), when there was evidence of active disease. The FDA approved Lucentis in 2006. However, most clinicians adopted PRN dosing for Lucentis, which was a departure from FDA-approved labeling and the monthly dosing schedule evaluated in the Genentech-sponsored clinical trials. It was not known if PRN dosing would produce the same long-term vision benefits that were achieved with monthly administration. NEI launched CATT in 2008 to compare Lucentis and Avastin for treatment of wet AMD. The study has now reported results for 1,185 patients treated at 43 clinical centers in the United States. Patients were randomly assigned and treated with one of four regimens for a year. They received Lucentis monthly or PRN, or Avastin monthly or PRN. Enrollment criteria required that study participants had active disease. Patients in the monthly dosing groups received an initial treatment and then had an injection every 28 days. Patients in the PRN groups received an initial treatment and were then examined every 28 days to determine medical need for additional treatment. PRN groups received subsequent treatment when there were signs of disease activity, such as fluid in the retina. Ophthalmologists involved in patient care did not know which study drug a patient was getting, to make sure that the data was not affected by how anyone felt about the treatment. Change in visual acuity served as the primary outcome measure for CATT. Thus far, visual acuity improvement was virtually identical (within one letter difference on an eye chart) for either drug when given monthly. In addition, no difference was found in the percentage of patients who had an important gain or loss in visual function. Also, when each drug was given on a PRN schedule, there also was no difference (within one letter) between drugs. PRN dosing required four to five fewer injections per year than monthly treatment. Visual gains were about two letters less with PRN than with monthly treatment, but overall visual results were still excellent. Investigators in the CATT study will continue to follow patients through a second year of treatment. These additional data will provide information on longer-term effects of the drugs on vision and safety. The FDA has not evaluated data from the CATT trial. Source: EurekAlert! 4/28/11 See also "Cheaper eye drug proves as good as pricier one"; and "Patient Group AMD Alliance International Responds to CATT Trials Research"

Phase II Nasal Spray Results Show Promise for Seasonal Allergic Rhinitis

ISTA Pharmaceuticals, Inc. in April announced positive, topline results from its Phase II clinical trial of bepotastine besilate nasal spray for the treatment of symptoms associated with seasonal allergic rhinitis, the inflammation of the nasal passages caused by allergies. According to the trial findings, each of three concentrations of bepotastine besilate nasal spray showed statistically significant improvements compared to placebo in patients' nasal symptoms following exposure to Mountain Cedar pollen during the peak season for this allergen. These improvements were seen on day one of therapy and were sustained through the two-week treatment period. Further, safety data demonstrated bepotastine besilate was well-tolerated as a nasal spray, with an adverse event profile similar to placebo and consistent with those observed with bepotastine besilate dosed as a nasal spray in prior clinical trials and with other antihistamine nasal sprays. According to the company, the next step in the development plan for this drug candidate is to explore clinical study designs for a bepotastine besilate/steroid combination nasal spray and, after completing discussions with the Food and Drug Administration, initiating a Phase II study in Mountain Cedar pollen with a bepotastine besilate/steroid combination nasal spray before the end of 2011. The latest trial was a randomized, multicenter, double-masked, placebo-controlled, dose-ranging, parallel-group, environmental study to evaluate the safety and efficacy of bepotastine besilate, dosed twice daily, in patients presenting with allergic rhinitis caused by Mountain Cedar pollen. Following initial screening for evidence of Mountain Cedar pollen allergy, approximately 600 patients in Texas, aged 12 years and older, were treated twice per day with one of three concentrations of bepotastine besilate nasal spray or placebo for two weeks. Patients graded both individual nasal and ocular symptoms on a daily basis. In addition to reducing total nasal symptoms, statistically significant improvements were seen for all three concentrations compared to placebo in terms of total ocular symptoms. ISTA expects to report comprehensive data from the trial at an appropriate, peer-reviewed forum in the near future. Source: Marketwire 4/28/11

Results Announced for Colorectal Cancer Study

Radient Pharmaceuticals Corp. in April announced the results of its analysis of data from the U.S. clinical trial conducted in collaboration with a large and well-recognized third-party not-for-profit group practice and its affiliates for the company's Onko-Sure® in vitro diagnostic (IVD) cancer test. Based on the final trial analysis, it has been determined that Onko-Sure (DR-70) is a useful tool when combined with carcinoembryonic antigen (CEA) in detecting colorectal cancer in all stages and, specifically, in early stages I and II, where early diagnosis and treatment can lead to better patient prognosis. Additionally, the study demonstrated that the cancer test can be up to 17 percent more effective in detecting the disease in these early stages than CEA. Furthermore, the study showed that when Onko-Sure is combined with CEA, the sensitivity of the combined tests delivers additional increased sensitivity as opposed to using CEA alone. The company RPC plans to disseminate these results in a peer-reviewed journal, either independently or with other third-party healthcare organizations. Additionally, it plans to present these results to physicians at international oncology conferences and scientific meetings. Source: Marketwire 4/27/11

Adding Drug to Chemo for Prostate Cancer Fails

A data and safety monitoring committee (DSMC) has determined that patients in a Phase III clinical trial given atrasentan in addition to a standard chemotherapy regimen for advanced prostate cancer did not have longer survival or longer progression-free survival than patients on the same chemotherapy regimen who received a placebo rather than atrasentan. Almost 1,000 patients who had advanced, hormone-refractory prostate cancer were given up to 36 weeks of chemotherapy with docetaxel and prednisone. These patients were randomized so that one half received an additional pill with a dose of atrasentan while the other half received a placebo pill. Patients who completed their chemotherapy and showed no progression of the disease were given the option of continuing the additional blinded pill (atrasentan or placebo). The study's DSMC evaluated a planned interim analysis of trial data and determined the evidence indicating no benefit from the drug was strong enough to close the study early, rather than waiting another 18 months as originally planned. The DSMC found no evidence that the drug was harming patients. New patient enrollment to the study stopped in April 2010, and few patients continue to take the study pill. Patients still taking study medication should speak to their doctor about stopping safely and what to do with their remaining pills. Treatment assignment is being unblinded, so patients can learn from their study doctor whether they took atrasentan or a placebo. The study was supported by the National Cancer Institute (NCI) and conducted by SWOG (formerly the Southwest Oncology Group) with the participation of several other NCI cooperative groups. Atrasentan for the trial was provided under an agreement with Abbott Laboratories and was distributed by the Department of Veterans Affairs Cooperative Studies Program Clinical Research Pharmacy Coordinating Center. Source: EurekAlert! 4/21/11

Company Initiates First Human Trial in Lupus Program

Dynavax Technologies Corporation announced in April the start of dosing in the first human clinical trial in its lupus program. Initiation of this trial entitles Dynavax to receive a $6 million milestone payment from GlaxoSmithKline (GSK), its partner in a worldwide strategic alliance. GSK has an exclusive option to obtain a license to the program. Dynavax's Phase I study will assess the safety of DV1179, an inhibitor of TLR7 and TLR9, in multiple ascending doses. A total of 24 healthy subjects, divided into three dose groups, will each receive four weekly injections of DV1179. Data from this study are expected later this year. Following successful completion of the trial, Dynavax expects to initiate a proof-of-mechanism study in lupus patients. Dynavax's TLR inhibitors are a novel class of oligonucleotides, called immunoregulatory sequences, which specifically inhibit the TLR-induced inflammatory response associated with autoimmune and inflammatory diseases. Preclinical data from animal model studies show Dynavax's TLR inhibitors block induction of IFN-alpha and also reduce symptoms in animal models of multiple autoimmune diseases, such as lupus, inflammatory skin disorders, and rheumatoid arthritis. The National Institutes of Health in Bethesda, Md., and the Alliance for Lupus Research contributed funding for Dynavax's preclinical work. Source: Marketwire 4/20/11

FDA Approves Device Treatment for Recurrent Glioblastoma

Novocure in April announced that the U.S. Food and Drug Administration (FDA) approved the NovoTTF-100A System (NovoTTF) for the treatment of adult patients with glioblastoma multiforme (GBM) brain tumors, following tumor recurrence after receiving chemotherapy. The portable, wearable device delivers an antimitotic, anticancer therapy as patients maintain their normal daily activities. The NovoTTF is a novel, first-in-class treatment option for patients and physicians battling glioblastoma. Results from a 237-patient randomized pivotal trial demonstrated that, compared to patients treated with chemotherapy, NovoTTF-treated patients achieved comparable median overall survival times, had fewer side effects, and reported improved quality-of-life scores. Specifically, quality of life using the device was better than that of chemotherapy patients in the following subscale domains: vomiting, nausea, pain, diarrhea, constipation, cognitive functioning, and emotional functioning, all of which are hallmarks of patient suffering while receiving chemotherapy. The most commonly reported side effect from NovoTTF treatment was a mild-to-moderate rash beneath the electrodes. Source: EurekAlert! 4/15/11

New Drug May Reduce Seizures in Epilepsy

A new drug called perampanel appears to significantly reduce seizures in people with hard-to-control epilepsy, according to results of the first clinical trial to test the higher 12 mg dose of the drug. The late-breaking research was presented at the 63rd Annual Meeting of the American Academy of Neurology in April in Honolulu, Hawaii. The study involved 387 people in the United States and Latin America who had uncontrolled epilepsy and were currently taking one to three other antiseizure drugs. Participants were assigned to receive either eight or 12 mg of perampanel or a placebo pill once daily for 19 weeks in addition to their regular treatment. Patients who took the 12 mg-dose of perampanel had a 14 percent reduction in seizures in a 28-day period compared to those who took the placebo. Those who took the 8 mg-dose cut their seizure frequency by nearly 6 percent compared to those who took the placebo. The most common side effects of the drug were dizziness, drowsiness, irritability, headache, falls and ataxia, which is a lack of muscle coordination. The drug's manufacturer, Eisai Inc., supported the study and plans to submit the drug for Food and Drug Administration approval this year. Source: EurekAlert! 4/13/11

Oral Drug for MS Significantly Reduces Disease Activity and Slows Disability

The drug laquinimod reduced the number of relapses for people with multiple sclerosis (MS) in a large, long-term Phase III clinical study that was presented as late-breaking research at the 63rd Annual Meeting of the American Academy of Neurology in April in Honolulu, Hawaii. The study involved 1,106 people with relapsing-remitting MS in 24 countries. The participants received either a once-daily oral dose of 0.6 mg of laquinimod or a matching placebo for two years. Eighty percent of those taking laquinimod and 77 percent of those taking the placebo finished the two-year study. Patients treated with laquinimod experienced a statistically significant reduction of 23 percent in annual relapse rate, compared to patients treated with a placebo. Additionally, there was a reduction of 36 percent in disability progression, as well as a 33 percent reduction in brain atrophy for those people treated with laquinimod. Researchers credit the results to the novel mechanism of action of laquinimod, which "effectively and safely addressed both the acute inflammatory activity and the accumulation of irreversible tissue damage." The incidence of liver enzyme elevation was higher in laquinimod-treated patients, but these elevations were temporary, reversible, and did not lead to any signs of liver problems. The study was supported by Teva Pharmaceuticals. Source: EurekAlert! 4/11/11

Phase III Trial Results Disappointed for Huntington Disease Effort

Pfizer Inc. and Medivation, Inc. in April announced results from the Phase III HORIZON trial of the investigational drug dimebon (latrepirdine) in patients with Huntington disease. Dimebon did not achieve statistical significance for either of the coprimary endpoints, the Mini-Mental State Examination (MMSE), which measures cognition, or the Clinician's Interview-Based Impression of Change, plus caregiver input, which measures global function. "We are disappointed with the results of the HORIZON trial given the high unmet need in this patient population. At this point, we will discontinue development of dimebon in Huntington disease, including the ongoing open-label extension study," said David Hung, MD, president and chief executive officer of Medivation. "We will continue our ongoing 12-month Phase III CONCERT trial of dimebon and its open-label extension in patients with mild-to-moderate Alzheimer's disease. We expect to report top-line data from CONCERT in the first half of 2012." Dimebon was generally well tolerated in the HORIZON trial, consistent with findings from previous trials including more than 2,000 patients, the large majority of whom were Alzheimer's disease patients. "Huntington's is a challenging disease area, and we are also disappointed with the HORIZON results," said Pfizer's Steve Romano, MD, senior vice president, Medicines Development Group head, Primary Care Business Unit. "The results are expected to be presented at an upcoming medical meeting." The double-blind, placebo-controlled HORIZON trial enrolled 403 patients with Huntington disease at 64 sites in North America, Europe, and Australia. The trial included patients who had cognitive impairment, based on investigator judgment and verified by MMSE score. Patients were randomized to receive either 20 mg of dimebon three times daily or placebo for six months. The trial was conducted in collaboration with the Huntington Study Group and the European Huntington's Disease Network. Source: Marketwire 4/11/11

IPF Drug Falls Short in New Trial

A new study has demonstrated no significant benefit of taking the drug bosentan for idiopathic pulmonary fibrosis (IPF). The results were published online ahead of the print edition in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine. Although the primary endpoint of the Bosentan Use in Interstitial Lung Disease (BUILD)-3 study was not attained, researchers point to the possibility of benefit for a subset of IPF patients who had undergone surgical lung biopsy to confirm their diagnosis. The study, however, had insufficient power to confirm this finding. Three years ago, the BUILD-1 trial, a prospective, double-blind, placebo-controlled trial designed to determine whether bosentan could improve six-minute walk distances in IPF patients after one year, failed to demonstrate a difference in six-minute walk distances, but a post-hoc analysis suggested that patients who underwent surgical lung biopsy to confirm their IPF diagnosis had improvements in their health-related quality of life and delayed worsening of their IPF. The BUILD-3 trial was designed to refine the patient population that appeared to benefit from bosentan in BUILD-1 and assess the effects of the drug more precisely. The randomized, double-blind, placebo-controlled study enrolled a total of more than 600 patients who were randomized 2:1 to receive bosentan or a placebo. Patients were eligible if they had mild-to-moderate IPF, confirmed by surgical lung biopsy, for three years or less. Patients with extensive honeycombing (indicating more advanced disease) were excluded. Each patient was assessed at baseline, at randomization, and every four months thereafter until the conclusion on the study. The primary endpoint of the study was IPF worsening or all-cause death. Secondary endpoints included changes in health-related quality of life, time to IPF worsening, and time to death. The patients were followed for a mean of 19.9 months until the end of the study, which was predetermined to be when 202 IPF-related "events"—that is, worsening or death—occurred. There was no significant difference between treatment and placebo groups for time to death or to IPF worsening. Health-related quality of life scores were also not significantly different between groups. There is hope that endothelin antagonists, alone or in combinations with other antifibrotic agents, can benefit a certain subpopulation of people with IPF; the researchers' goal moving forward to is to identify that population more precisely. Source: EurekAlert! 4/8/11

Enrollment Initiated for Proof-of-Concept Trial in Retinal Detachment

Lpath, Inc. has initiated enrollment in its PEDigree clinical trial of iSONEP™, the company's ocular drug candidate with which it has partnered with Pfizer. In this Phase Ib/IIa trial, Lpath plans to dose 32 subjects that have retinal pigment epithelium detachment (PED) that is secondary to wet age-related macular degeneration (wet AMD) or polypoidal choroidal vasculopathy (PCV). PED is a potentially serious condition that is often part of the pathology of wet AMD and PCV, yet no drug has yet been approved to treat PED. Even though patients with PED were excluded from the Lucentis® pivotal trials, this drug is often used to treat such patients, but with incomplete success. In addition, PCV frequently does not respond well to Lucentis and is often misdiagnosed as wet AMD. Subjects in the PEDigree trial will receive up to three monthly intravitreal injections of iSONEP, and two dose levels will be tested. The primary safety endpoint is the tolerability of consecutive monthly injections, and the primary efficacy endpoint is the percentage of subjects that experience flattening of their PED. In Lpath's Phase I trial, where subjects with wet AMD received only one injection, iSONEP met its primary endpoint of being well tolerated in all 15 patients. It also succeeded in meeting a key secondary endpoint in that a positive biological effect--with a single dose--was observed in most patients, almost all of whom had failed to respond to Lucentis and/or Avastin® treatment. Lpath plans to begin another iSONEP trial in June of this year, a Phase II proof-of-concept trial to study the efficacy and safety of iSONEP in wet AMD patients who do not have PED. Source: Marketwire 4/7/11

Phase IIb Trial Starts in Parkinson's Disease

Biotie Therapies Corp. in April announced the start of a Phase IIb trial evaluating SYN115 in Parkinson's disease (PD). Results from the study are expected in the first half of 2013. SYN115 is an orally bioavailable potent and selective adenosine A2a receptor antagonist. Adenosine A2a inhibition has been shown in preclinical studies to reverse motor deficits and enhance the effect of current PD therapies, e.g. levodopa and dopamine agonists, without inducing troublesome dyskinesia (involuntary movements). In addition, SYN115 displays activity in preclinical models on nonmotor symptoms of PD including depression, cognition, and anxiety. The new trial is a randomized, double-blind, placebo-controlled study that will evaluate four doses of SYN115 versus placebo as adjunctive therapy in 400 levodopa-treated PD patients with end of dose wearing off. In these patients, treatment with levodopa is insufficient to control PD symptoms until their next dose, resulting in an "off" period when symptoms reappear. The aim of the study is to determine the efficacy and safety of SYN115 in reducing the mean time spent in the "off" state over a 12-week treatment period. The trial will also assess the impact of SYN115 on various measures of motor symptom severity, dyskinesia, and nonmotor symptoms. Source: Marketwire 4/7/11

International Enrollment Under Way for Stent System

Boston Scientific Corp. in April announced the start of patient enrollment in the SuperNOVA clinical trial, an international, prospective, single-arm, nonrandomized trial evaluating the safety and effectiveness of the Innova™ self-expanding bare-metal stent system in patients with stenosis of the superficial femoral artery (SFA) or proximal popliteal artery (PPA). Enrollment is planned for up to 300 patients at 50 sites in the U.S., Canada, and Europe. The first patient was enrolled in the trial by Subhash Banerjee, MD, associate professor of medicine and chief of cardiology at the VA Medical Center in Dallas, Texas. The Innova system is designed to treat peripheral vascular lesions in arteries above the knee, specifically the SFA and PPA. It consists of a nitinol, self-expanding bare-metal stent loaded on an advanced low-profile delivery system. The stent system received CE Mark in March, and the company plans to begin marketing the product in the European Union and other countries in the second quarter of 2011. In the U.S., it is an investigational device, limited by applicable law to investigational use only and not available for sale. Source: PRNewswire 4/5/11

Multicenter Trial for Sleep Apnea Therapy Yields Positive Results

Ventus Medical, Inc. in April reported positive results from a 19-center clinical trial of 250 patients using its Food and Drug Administration-cleared Provent® sleep apnea therapy device to treat obstructive sleep apnea. Provent uses the patient's own breathing to create expiratory positive airway pressure to keep the airway open during sleep. The full results of this three-month study were published in the April 2011 issue of the peer-reviewed medical journal SLEEP. The prospective, randomized, double-blind, sham-controlled study demonstrated that Provent therapy significantly improved the apnea hypopnea index (AHI), a scale to measure the number of breathing interruptions or stoppages per hour of sleep, as well as subjective sleepiness, as measured by the Epworth Sleepiness Scale, in patients with obstructive sleep apnea. Self-reported patient adherence on Provent therapy was 88.2 percent. Results at the start of the study showed that AHI was reduced by 52.7 percent in the Provent therapy group compared to a 7.3 percent reduction in the sham group, representing a highly significant treatment effect. Using the Epworth Sleepiness Scale to evaluate daytime sleepiness, patients using Provent therapy showed improved alertness, reducing sleepiness from 9.9 +/- 4.7 to 7.2 +/- 4.2 compared to the sham group of 9.6 +/- 8.3 to 8.3 +/- 5.1 , a statistically significant improvement compared to the sham group. Source: PRNewswire 4/4/11

Results are Promising from Anticoagulation System Study

Regado Biosciences, Inc. announced in April the primary results of the RADAR Phase IIb clinical trial of the company's lead product, the anticoagulation system REG1, at the i2 Summit during the American College of Cardiology 2011 60th Annual Scientific Session & Expo in New Orleans, La. REG1 is a two-component system consisting of pegnivacogin (a highly selective Factor IXa [FIXa] inhibitor) and anivamersen (its complementary specific active control agent). The international trial was conducted in subjects admitted for acute coronary syndrome (ACS)-unstable angina and myocardial infarction without ST-segment elevation intended for cardiac catheterization within 24 hours. The objectives of RADAR were to verify that 1 mg/kg of pegnivacogin resulted in near complete FIXa inhibition, to determine the dose of anivamersen which, when followed by immediate arterial sheath removal, results in a bleeding rate lower than heparin, and to assess the efficacy of REG1 (based on ischemic event rates) as an anticoagulation system in an invasively managed ACS population. The primary endpoint of the study was ACUITY bleeding (major and minor) at 30 days. A secondary endpoint was a composite of death, myocardial infarction, urgent target vessel revascularization, or recurrent ischemia at 30 days. The latest results showed that ACUITY major bleeding following immediate sheath removal exhibited a dose response with bleeding rates decreasing with increasing levels of reversal. Rates of bleeding were lower in the 75 percent and 100 percent reversal arms than heparin. In addition, the incidence of ischemic events was lower in REG1-treated patients compared to those treated with heparin. Source: PRNewswire 4/3/11

Positive Phase II Results Announced for Monotherapy in Primary Biliary Cirrhosis

Intercept Pharmaceuticals, Inc. in late March announced positive results from a 59-patient, placebo-controlled, double-blind Phase II clinical trial, involving 20 centers in seven countries, of obeticholic acid (OCA) given as monotherapy to patients with primary biliary cirrhosis (PBC). The study evaluated the effects of 10 mg and 50 mg of OCA compared to placebo in patients with elevated alkaline phosphatase (AP), a liver enzyme routinely used to evaluate the clinical status and disease progression of PBC patients. At the end of the 12-week treatment period, both doses of OCA produced statistically highly significant reductions in AP, the primary endpoint, compared to the patients receiving placebo. There were also significant improvements in other liver enzymes, including gamma-glutamyl transferase. In addition, serum markers of inflammation and immunity improved, with significant reductions of C-reactive protein and immunoglobulin M (IgM), which is closely associated with the autoimmune dysfunction in PBC. Pruritus (itch) was seen more commonly in the OCA treated patients and increased with dose; otherwise, all other adverse events were generally similar across the 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 in developed countries. There is only one drug approved to treat the disease, ursodeoxycholic acid (UDCA), and up to 50 percent of PBC patients on UDCA therapy continue to be at significant risk of progression to cirrhosis. Source: PRNewswire 3/31/11

Top-Line Results Fall Short in Phase III NSCLC Trial

Amgen, Millennium: The Takeda Oncology Company, and Takeda Pharmaceutical Company Limited in late March announced top-line results from the MONET1 pivotal Phase III trial evaluating motesanib administered in combination with paclitaxel and carboplatin in 1,090 patients with advanced non-squamous non-small cell lung cancer (NSCLC). The trial did not meet its primary objective of demonstrating an improvement in overall survival. "We are disappointed with the results from this trial, but look forward to further analysis of the data, which may ultimately help inform future research in this area," said Roger M. Perlmutter, MD, PhD, executive vice president of research and development at Amgen. "We thank the patients, caregivers, and investigators for their participation and engagement in the clinical evaluation of motesanib worldwide," said Nancy Simonian, MD, chief medical officer for Millennium. "These disappointing results support the need for new treatments to address the unmet need in advanced non-squamous NSCLC." Detailed results will be submitted for presentation at an upcoming medical congress. MONET1 was a multicenter, randomized, placebo-controlled, double-blind trial with patients randomized to receive either paclitaxel (200 mg/m2 IV Q3W), carboplatin (target AUC of 6 mg/mL x min IV Q3W), and motesanib (125 mg PO QD) or paclitaxel, carboplatin, and placebo. Secondary endpoints included progression-free survival, objective response rate, association of placental growth factor with overall survival, duration of response, and safety and tolerability. Motesanib is an investigational, orally administered small molecule antagonist of vascular endothelial growth factor receptors 1, 2, and 3, platelet-derived growth factor receptors, and stem cell factor receptor. Source: PRNewswire 3/30/11

Companies Announce Initiation of Phase II Comparing Advanced Prostate Cancer Treatments

Medivation, Inc. and Astellas Pharma Inc. in late March announced treatment of the first patient in the TERRAIN study, a Phase II comparison of the investigational drug MDV3100, a triple-acting oral androgen receptor antagonist, to bicalutamide, a commonly used anti-androgen, in the treatment of advanced prostate cancer patients who have progressed while on LHRH analogue therapy or following surgical castration. MDV3100 is currently in Phase III testing for advanced prostate cancer, but the goal of the comparison study is to determine if MDV3100 can benefit men with prostate cancer earlier in the course of the disease. TERRAIN is expected to enroll approximately 370 patients in North America and Europe. The primary endpoint of the trial is progression-free survival. A second new Phase II trial, expected to begin in the first half of 2011, will study MDV3100 in an even earlier-stage population--hormone-naïve prostate cancer patients who are indicated for androgen deprivation therapy. The randomized, double-blind, placebo-controlled Phase III AFFIRM trial completed enrollment in November 2010. This trial of 1,199 patients with advanced prostate cancer who were previously treated with docetaxel-based chemotherapy is evaluating 160 mg/day of MDV3100 versus placebo. The primary endpoint is overall survival. A second Phase III clinical trial of MDV3100 in advanced prostate cancer, the PREVAIL trial, is currently enrolling patients. This randomized, double-blind, placebo-controlled, multinational trial of approximately 1,700 men with advanced prostate cancer who have not yet received chemotherapy is evaluating MDV3100 at a dose of 160 mg taken orally once daily plus standard of care versus placebo plus standard of care. The co-primary endpoints of the trial are overall survival and progression-free survival. Source: Marketwire 3/30/11

Laser Study Shows Signs of Relief for Psoriasis Patients

PhotoMedex, Inc. announced in late March the implications of the preliminary findings of a current clinical trial being performed by John Y.M. Koo, MD, professor and vice chairman, department of dermatology, University of California, San Francisco. Dr. Koo's experimental treatment protocol aims to help people suffering from moderate to severe psoriasis. Results from the study to date, which utilizes the XTRAC® Velocity 700 laser from PhotoMedex in combination with clobetasol spray (Clobex®) and calcitriol (Vectical®), were presented by Dr. Koo during the 20th Annual Meeting of the Photomedicine Society. While the study plans to enroll a total of 30 patients, preliminary results were presented for the first patients recruited--seven patients who completed six weeks of treatments and four who completed 12 weeks of treatments. Of the seven patients who completed six weeks of the treatments, six of them experienced 75 percent clearing of their moderate to severe psoriasis. The four patients who completed 12 weeks of treatments all achieved 75 percent clearing. The XTRAC laser is the only excimer laser that is clinically proven, Food and Drug Administration-cleared, and quality-certified for targeted phototherapy treatment for psoriasis and vitiligo. According to the company, the treatment offers psoriasis sufferers long-lasting relief, with remission times averaging four to six months and many times exceeding one year. Source: PRNewswire 3/29/11

Transdermal System Investigated in Opioid-Naive Back Pain Patients

Physicians from Purdue Pharma LP in March showcased study results that demonstrate the analgesic efficacy and safety of Butrans for the relief of moderate to severe chronic low back pain in opioid-naive patients. Butrans is a transdermal delivery system that provides systemic delivery of buprenorphine, a Schedule III medication, continuously over a seven-day period. Butrans was approved by the Food and Drug Administration in June 2010. The new randomized, double-blind, 12-week study employed an enriched design. A total of 1,024 patients were treated with Butrans during the open-label run-in period and were randomized to Butrans 10 and Butrans 20, or matching placebos. Age, gender, and weight were equally distributed across the two treatment groups. In the open-label run-in period, if Butrans 10 was tolerated but adequate analgesia was not reached, the dose was increased to Butrans 20 for an additional 10 to 12 days. Patients who achieved adequate analgesia and tolerated Butrans were then randomized to remain on the titrated dose of Butrans (10 or 20) or a matching placebo. To demonstrate adequate analgesia in the open-label run-in period, patients had to have pain scores of less than or equal to 4 on an 11-point scale for three consecutive days and at least a two-point reduction from their screening pain scores. The primary efficacy outcome, the "average pain over the last 24 hours" at Week 12, resulted in a statistically significant treatment difference of -0.58 in favor of Butrans over placebo. The proportions of patients with at least 30 percent and at least 50 percent pain score improvements were larger for Butrans-treated patients. Source: PRNewswire 3/25/11

Tuberculosis Diagnostic Test is Focus of Progress Update

Signature Mapping Medical Sciences Inc.'s TBDx tuberculosis (TB) diagnostic system is in the final stages of an independently controlled clinical trial, which is nested as a substudy to the large international Thibela TB trial being conducted by the Aurum Institute. A detailed progress update provided by Aurum to Signature Mapping and its parent company, Applied Visual Sciences, Inc., is available at www.appliedVS.com. Among other details, preliminary findings from the ongoing study suggest that TBDx may well be best placed as a "front-end" screening technology before the use of newer. but more expensive. diagnostic technologies. A routine, high-volume laboratory demonstration project protocol has already been developed to follow on from the main scientific study pending results from this study. The results of the study are expected to start rolling out in April 2011. If successful, this will be the world's first fully automatic TB diagnostic microscopy system, and will establish the underlying Signature Mapping technology as a valid platform on which to develop a host of other image-based disease diagnostics. Source: Marketwire 3/24/11

Mixed Results Seen in Phase IIb Top-Line Results for Type 2 Diabetes

XOMA Ltd. in March announced that its Phase IIb trial of XOMA 052 in type 2 diabetes patients did not achieve the primary endpoint of reduction in glycosylated hemoglobin (HbA1c) after six monthly treatments with XOMA 052 compared to placebo. The randomized, placebo-controlled, dose-ranging trial enrolled 421 patients at multiple sites in the United States during 2010. Biological activity of XOMA 052 supporting its potential in cardiovascular disease was observed with highly significant decreases in C-reactive protein, a biomarker for the risk of heart attack, stroke, and other cardiovascular diseases, in all dose groups versus placebo. In addition, statistically significant improvements in high-density lipoprotein, or "good" cholesterol, were observed in two of four XOMA 052 dose groups versus placebo. XOMA is developing XOMA 052 in collaboration with Servier. "While this trial did not demonstrate glycemic improvement, the potent anti-inflammatory effects and continued positive safety profile reinforce our Phase III development program for Behcet's uveitis, which we anticipate starting this year pending completion of regulatory agency discussions. We are also encouraged by the improvements in C-reactive protein and 'good' cholesterol, which support the further evaluation of XOMA 052 in cardiovascular disease and other inflammatory indications," said Steven B. Engle, XOMA's chairman and chief executive officer. Source: Globe Newswire 3/22/11

Phase I Clinical Testing of H1N1 Vaccine Under Way

Medicago Inc. in Marh announced that the first dose of vaccine has been administered to initiate the company's Phase I H1N1 influenza virus-like particle vaccine candidate clinical trial in the United States. The primary safety and immunogenicity results for this trial are expected within three months. The randomized, double-blind, multicenter, active- and placebo-controlled dose-ranging study will evaluate the safety, tolerability, and immunogenicity of a single nonadjuvanted dose of the H1N1 vaccine in 100 healthy adults 18 to 49 years of age. The subjects will be randomized to receive either an injection of the placebo, Medicago's H1N1 vaccine, or an H1N1 vaccine from a licensed trivalent vaccine. This trial will lead into Medicago's U.S. Phase IIa trial for its seasonal trivalent vaccine with the recommended H1N1, H3N2, and B influenza strains, which the company plans to conduct later in 2011. Source: PRNewswire 3/21/11

Heart Improves After Stem Cell Injections in Preliminary Trial

Researchers have shown for the first time that stem cells injected into enlarged hearts reduced heart size, reduced scar tissue, and improved function to injured heart areas, according to a small trial published in Circulation Research: Journal of the American Heart Association. Researchers said that while this research is in the early stages, the findings are promising for the more than 5 million Americans who have enlarged hearts due to damage sustained from heart attacks. Joshua M. Hare, MD, is the study's senior author and professor of medicine and director of the Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine in Florida. Using catheters, researchers injected stem cells derived from the patient's own bone marrow into the hearts of eight men (average age 57) with chronically enlarged, low-functioning hearts. The effects lasted for a year after the injections, which was the full duration of the study. Specifically, researchers found that heart size decreased an average of 15 percent to 20 percent, which is about three times what is possible with current medical therapies; scar tissue decreased by an average of 18.3 percent; and there was dramatic improvement in the function, or contraction, of specific heart areas that were damaged. "This therapy improved even old cardiac injuries," Hare said. "Some of the patients had damage to their hearts from heart attacks as long as 11 years before treatment." The researchers had used two different types of bone marrow stem cells in their study—mononuclear or mesenchymal stem cells. The study lacked the power to determine if one type of cell works better than the other. All patients in the study benefited from the therapy and tolerated the injections with no serious adverse events. The stem cell institute, BioCardia (makers of the catheter used), and the National Institutes of Health funded the study. Source: PRNewswire 3/17/11

Sponsors Voluntarily Suspend Clinical Activities in Obesity Trial

Amylin Pharmaceuticals, Inc. and Takeda Pharmaceutical Co. Ltd. in March announced that they have suspended clinical activities in an ongoing Phase II study examining the safety and effectiveness of the investigational combination therapy pramlintide/metreleptin for the treatment of obesity. The clinical study was voluntarily halted to investigate a new antibody-related laboratory finding with metreleptin treatment in two patients who participated in a previously completed clinical study of obesity. "The safety of patients in our clinical programs is of paramount concern to the companies. We have taken this precaution so that we can thoroughly investigate this finding," said Orville Kolterman, MD, senior vice president and chief medical officer of Amylin Pharmaceuticals. "Together with our partner, Takeda, we are committed to working closely with clinical investigators, regulators, and outside experts to determine the best path forward." Pramlintide acetate is a synthetic analog of the natural hormone amylin, a neurohormone secreted by the pancreas that is known to play a role in the regulation of appetite, food intake, and postprandial glucose concentrations. To date, approximately 8,000 individuals have received pramlintide in clinical trials, including more than 950 in obesity studies. Metreleptin (methionyl recombinant leptin; r-metHuLeptin) is an analog of human leptin, a neurohormone secreted by fat cells that plays a fundamental role in the regulation of energy metabolism and body weight. To date, more than 1,200 overweight or obese individuals have received metreleptin in clinical trials, several of which were 16 weeks or longer in duration. Source: PRNewswire 3/16/11

Company Receives Approval to Commence Phase I Alzheimer's Trial

Anavex Life Sciences Corp. in March announced that its clinical trial application for ANAVEX 2-73, the company's lead compound for Alzheimer's disease, has been approved by the German regulatory health authority, BfArM. The Phase I trial, which includes testing in healthy human volunteers, will commence immediately. In this program, Anavex will assess safety, maximally tolerated dose, pharmacokinetics, and pharmacodynamics. ANAVEX 2-73 is the first of a new class of wholly owned compounds that act through sigma-1 receptor agonism, as well as muscarinic and cholinergic effects and modulation of endoplasmic reticulum stress, to trigger a series of intracellular effects thought to modify ion channel signalling at the mitochondrial level. The trial will be carried out in collaboration with ABX-CRO and the University of Dresden in Germany. Source: PRNewswire 3/15/11

Phase II Study in Obsessive Compulsive Disorder Begins

Transcept Pharmaceuticals, Inc. in March announced the first patient has been enrolled in a Phase II clinical study to evaluate TO-2061 as an adjunctive treatment for obsessive compulsive disorder (OCD) in patients who have responded inadequately to currently approved treatments. OCD affects 1 to 2 percent of the U.S. adult population. Approximately 50 percent of patients do not respond adequately to standard first-line treatment with currently approved OCD medications, including the selective serotonin re-uptake inhibitors (SSRIs) and the tricyclic agent, clomipramine. There is no augmentation therapy approved by the Food and Drug Administration for these treatment-resistant patients. TO-2061 is a low-dose formulation of ondansetron, a serotonin subtype 3 (5-HT3) receptor antagonist. Ondansetron has an established history of clinical use as a safe and effective treatment for nausea and vomiting induced by chemotherapy, radiation therapy, and surgery, for which a typical daily dose is 16 mg to 24 mg. Transcept is studying ondansetron at reduced total daily doses of 1 mg to 1.5 mg as an adjunctive treatment of OCD. Eric Hollander, MD, clinical professor of psychiatry and behavioral sciences at the Albert Einstein College of Medicine, Montefiore Medical Center, is principal investigator for the study. Transcept says it is encouraged by the outcome of two open-label studies of low doses of ondansetron in treatment-resistant OCD, and now seeks to confirm these results in a double-blind, placebo-controlled, multicenter proof-of-concept trial. Approximately 150 OCD patients will be randomized into three groups to evaluate the safety and efficacy of TO-2061 compared to placebo. Patients with a documented history of at least six weeks of inadequate response to their current OCD medication will continue to receive that OCD medication for an additional six-week run-in phase of the study. Those patients who fail to respond to this course of therapy will then be eligible to enter the 12-week active treatment phase, during which they will continue to receive their first-line therapy with the addition of ondansetron 0.5 mg twice per day, ondansetron 0.75 mg twice per day, or placebo. The primary endpoint of the study is the difference between active and placebo treatment arms as measured by the Yale-Brown Obsessive Compulsive Scale. Source: PRNewswire 3/14/11

Phase III Study in Type 1 Diabetes Did Not Meet Primary Endpoint

Tolerx, Inc. and GlaxoSmithKline in March announced that the Phase III DEFEND-1 study of otelixizumab, an investigational humanized anti-CD3 monoclonal antibody, did not meet the primary efficacy endpoint of change in C-peptide at month 12 in patients with new-onset autoimmune type 1 diabetes. Following preliminary review of the data, no new or unexpected treatment-related safety concerns have emerged during the DEFEND-1 study. Study investigators and regulatory agencies have been notified of the DEFEND-1 study outcome. GlaxoSmithKline will continue to explore additional dosing regimens to inform decisions about the future clinical development program for otelixizumab. New recruitment and dosing in the DEFEND-2 study, the ongoing confirmatory Phase III study with a design similar to DEFEND-1, has been suspended pending review of the DEFEND-1 results. DEFEND-1 is a randomized, placebo-controlled Phase III study of 272 patients, age 12 to 45, with new-onset type 1 diabetes. DEFEND-1 was conducted at more than 100 study centers throughout North America and Europe, and was designed to evaluate whether a single eight-day intravenous course of otelixizumab (3.1 mg), administered not more than 90 days after the initial diagnosis of autoimmune type 1 diabetes, preserved the function of insulin-producing beta cells in the pancreas, as measured by C-peptide. Measurement of C-peptide (a protein that shows how much insulin the body is producing) at 12 months after dosing was the primary endpoint in DEFEND-1 and is a well established surrogate measure of beta cell function and a recommended endpoint by the U.S. Food and Drug Administration and the American Diabetes Association. Source: PRNewswire 3/11/11

Positive Phase IIa Results Seen for TrkA Kinase Inhibitor in Psoriasis Vulgaris

Creabilis SA in March announced positive results from its Phase IIa study of its lead product CT327 in psoriasis vulgaris. CT327 is a novel topically applied TrkA kinase inhibitor developed using Creabilis' Low Systemic Exposure technology. The proof-of-concept study was conducted in the U.S. and Europe in psoriasis patients who were treated for an eight-week period. Forty-eight patients were treated topically with 0.1 percent w/w CT327 cream twice daily and nine patients treated with matching placebo. CT327 produced a good efficacy response across multiple endpoints, including Physician Global Assessment (PGA) and modified Psoriasis Area and Severity Index. In the PGA analysis, 33 percent of patients had "controlled disease" at the end of the treatment period compared to 8 percent at the start of the study, and the number of "severe or very severe" patients was reduced by 50 percent over the same period. For placebo, 7 percent of patients had "controlled disease" at the end of the study compared to 6 percent at the start. CT327 reported positive results from a Phase IIa study in atopic dermatitis late last year and further proof-of-concept clinical trials in pain are ongoing. Source: PRNewswire 3/10/11

Company Initiates Phase I/II Study of Dermal Patch for Parkinson's Disease

NeuroDerm, Ltd. announced in March the enrollment of the first group of patients in its Phase I/II clinical trial of ND0611, a new patch for the treatment of Parkinson's disease. ND0611, a proprietary carbidopa liquid formula administered via dermal patch, is designed to increase the bioavailability and efficacy of orally administered levodopa and thus improve treatment of Parkinson's disease. The double-blind, randomized, six-way crossover trial is designed to evaluate ND0611's safety, tolerability, levodopa bioavailability, and preliminary clinical efficacy when administered with the three most commonly used levodopa therapies (immediate-release Sinemet®, Sinemet®-CR, and Stalevo®) in 24 advanced Parkinson's disease patients. The company expects to complete this study by the end of 2011. This trial is supported by a grant of $1 million by the Michael J. Fox Foundation for Parkinson's Research as part of the foundation's Clinical Intervention Awards 2010 program. Source: PRNewswire 3/9/11

Medical Center Testing "Heat Therapy" for Premature Ejaculation

University Hospitals Case Medical Center is conducting the first ever pilot study to test a new procedure using "heat therapy" or local radiofrequency energy to treat premature ejaculation. The procedure is called image-guided neurothermal modulation, referring to the energy produced by radio waves directed with a probe to modulate or lessen the sensation of a nerve. In this novel study, patients will undergo CT imaging to guide a tiny electrode about the size of a needle to the dorsal penile nerve in the pelvis, which ultimately supplies nerve sensation to the skin of the penis. Radio waves will be intermittently transmitted through the electrode to lessen the sensation carried by the targeted nerve. The patients will be in a conscious sedation during the procedure, much like the sedation given for a colonoscopy. The nerve recovers over time from the procedure, so the effects of the treatment are not permanent. If the effects are beneficial, the next step for study will be permanent ablation. The medical center expects to enroll its first patient in the study in early March. Twenty-two patients will be enrolled in the study to test the safety of the procedure and to see if the procedure results in the expected benefits for patients. The study is funded by Neurotherm®, in cooperation with University Hospitals Case Medical Center. Source: EurekAlert! 3/8/11

Lung Cancer Investigator-Sponsored Trial Under Way

Peregrine Pharmaceuticals, Inc. in March announced the initiation of an investigator-sponsored trial for patients with chemotherapy-naive stage IV nonsquamous non-small cell lung cancer (NSCLC). This Phase Ib trial will treat up to 25 front-line NSCLC patients with Peregrine's investigational monoclonal antibody bavituximab in combination with the chemotherapeutic agents pemetrexed and carboplatin. Juneko E. Grilley-Olson, MD, is lead investigator of this trial and assistant professor of hematology and oncology at the University of North Carolina at Chapel Hill. In a prior Phase II trial treating 49 front-line NSCLC patients with bavituximab in combination with a different chemotherapeutic regimen, carboplatin and paclitaxel, overall tumor response rate was 43 percent as measured by RECIST criteria and median progression-free survival was 6.1 months. Currently, bavituximab is being evaluated in four randomized Phase II trials, including front-line NSCLC, second-line NSCLC, pancreatic cancer, and HCV and in two other investigator-sponsored trials in advanced liver cancer and HER2-negative metastatic breast cancer. In the new single-arm, open-label trial, patients with previously untreated locally advanced or metastatic nonsquamous NSCLC will receive up to six 21-day cycles of the drugs pemetrexed and carboplatin with weekly bavituximab until progression or toxicity. The primary endpoint of the study is to determine the safety, dose-limiting toxicity, and recommended Phase II dose of bavituximab in combination with carboplatin and pemetrexed in advanced nonsquamous NSCLC. Secondary endpoints include assessment of overall response rate measured by RECIST criteria, progression-free and overall survival, and exploratory biomarkers. Source: Marketwire 3/8/11

DNA Vaccine for Cervical Dysplasia Caused by HPV Enters Phase II

Inovio Pharmaceuticals, Inc. announced in March that it is initiating a Phase II clinical trial for its VGX-3100 DNA vaccine for cervical dysplasia and cancer caused by human papillomavirus (HPV). The study will assess adult females with cervical intraepithelial neoplasias (CIN) 2/3 or CIN 3 and biopsy-proven HPV types 16 or 18. CIN are precancerous stages of abnormal cells that precede cervical cancer. HPV types 16 and 18 are responsible for 70 percent of CIN 2/3 and cervical cancer incidences. The randomized, placebo-controlled, double-blind study will evaluate cervical tissue changes after three 6 mg doses of VGX-3100 are administered by injection in combination with Inovio's Cellectra® electroporation delivery device. A total of 148 patients will be enrolled in 25 study centers in the U.S., Korea, South Africa, Australia, and Canada. The primary endpoints of this study are to assess regression of cervical lesions to CIN 1 or less and clearance of HPV 16 or 18. The study will evaluate the efficacy of the vaccine in patients who receive VGX-3100 at zero, four, and 12 weeks compared to placebo recipients, based on a biopsy performed six months after the final vaccine dose. The study will also explore humoral and cell-mediated immune responses to VGX-3100 in blood samples taken prior to the first vaccine dose and periodically thereafter. Cervical samples will be analyzed for evidence of immune responses in the cervix at the beginning of the trial and subsequent intervals. Subjects will also be monitored for tolerability and safety. This trial is a follow-on to Inovio's Phase I dose-escalation study of VGX-3100, which achieved best-in-class immune responses. In that study, 13 out of 18 vaccinated subjects developed significant T-cell responses, with positive responses ranging from less than 100 to more than 5,000 SFU per million cells. In the third and highest dose group, five of six vaccinated subjects had strong T-cell responses. In addition, 15 of 18 vaccinated subjects developed antibody responses to at least one antigen with most subjects developing responses to two or more antigens. No DNA vaccine has previously achieved this rate of response. Source: PRNewswire 3/7/11

Drug Prolongs Progression-Free Survival in Incurable Head and Neck Cancer

Patients with incurable squamous-cell carcinoma of the head and neck (SCCHN) whose chemotherapy is no longer working, who are given zalutumumab, survive significantly longer without the disease progressing than patients receiving best supportive care (BSC). These findings from the first randomized trial of zalutumumab in patients with SCCHN, published online in the Lancet Oncology, support zalutumumab therapy as a treatment option for these patients. However, the findings also show that despite a nearly 30 percent improvement in overall survival in patients taking zalutumumab, this increase was not significantly different to patients given BSC. For patients with recurrent or metastatic SCCHN whose platinum-based chemotherapy is no longer working the prognosis is poor and they are considered incurable. Currently, there are no treatment options available to increase survival in this group of patients. Most head and neck cancers express the epidermal growth factor receptor (EGFR) which is linked to poor outcome. Zalutumumab is a monoclonal antibody that targets EGFR and has been shown to inhibit tumour growth in preclinical studies. Researchers at the Cliniques Universitaires Saint Luc, Brussels, Belgium, conducted a Phase III trial to assess the effect of zalutumumab on overall and progression-free survival in patients with recurrent or metastatic SCCHN after failure of chemotherapy, with 286 patients recruited from 67 centers across Europe, Brazil, and Canada being randomly assigned to zalutumumab plus BSC (191 patients) or BSC alone (95 patients). Zalutumumab treatment was associated with significantly better progression-free survival, but did not significantly increase overall survival (median overall survival: 6.7 versus 5.2 months). Importantly, a long-term progression-free survival benefit was achieved by a group of patients shown by a progression-free survival rate at six months of 20 percent in the zalutumumab group compared to 7.3 percent in the BSC group. Interestingly, progression-free survival and overall survival seemed to be longer in patients with high EGFR expression compared to low EGFR expression, a finding not reported in previous studies that should be investigated in further trials. Source: EurekAlert! 3/6/11

FDA Clears Company to Commence Clinical Studies for Asthma

Palatin Technologies, Inc. in March announced that the U.S. Food and Drug Administration (FDA) has cleared the company's request to begin a Phase IIa proof-of-concept human trial under an Investigational New Drug application using a subcutaneously administered formulation of PL-3994, an NPR-A agonist compound, in development for treatment of acute exacerbations of asthma. Palatin is seeking a development and marketing partner for PL-3994, which would include both the proof-of-concept trial for asthma and development of an inhalation formulation. Palatin does not intend to initiate either the proof-of-concept human trial or preclinical inhalation toxicity studies unless and until an agreement is reached with a development and marketing partner, or Palatin receives funding to support the proof-of-concept trial or preclinical inhalation toxicity studies from a third party, such as grant funding from an agency of the federal government. PL-3994 increases plasma cyclic guanosine monophosphate levels, a pharmacological response consistent with the effects of endogenous natriuretic peptides on cardiovascular function and smooth muscle relaxation. Source: PRNewswire 3/3/11

First Subject Dosed in Safety Testing Toward Major Depressive Disorder Trial

Neuralstem, Inc. has announced that the first subject has been dosed in a Phase Ia trial to evaluate the safety of its drug, NSI-189, which is being developed for the treatment of major depressive disorder and other psychiatric indications. NSI-189 is the lead compound in Neuralstem's neurogenerative small molecule drug platform. This phase of the trial is in healthy volunteers and seeks to determine the maximum tolerated single dose. "While current antidepressant therapies seek to modulate symptomatic brain chemistry, NSI-189 stimulates new neuron growth and aims to restore fundamental brain physiology," said Karl Johe, PhD, chief scientific officer and chairman of Neuralstem's Board of Directors. "It has the potential to directly address the pathology of the disease itself, potentially reversing the hippocampal atrophy associated with depression and other disorders." When the maximum tolerated single dose is determined, the trial will progress to the Ib phase, testing the safety of escalating doses of daily administration for 28 days in patients with major depressive disorder. The entire Phase I trial is expected to be approximately one year in duration. NS-189 is the first in a class of compounds that Neuralstem plans to develop into orally administered drugs for psychiatric disorders. This program has received significant support from both the Defense Advanced Research Projects Agency and the National Institutes of Health. Source: PRNewswire 3/1/11

Institute Obtains IRB Approval for Multisite Trial of Nutritional Supplement

Rock Creek Pharmaceuticals, a wholly owned subsidiary of Star Scientific, Inc., has been notified by the Roskamp Institute of Sarasota, Fla. that the institute has received institutional review board (IRB) approval to conduct a three-month, multisite clinical trial with Rock Creek's RCP-006 nutritional supplement formula. The study will enroll approximately 200 subjects in the region of Flint, Mich., and will examine the effect of RCP-006 on chronic inflammation in individuals who have elevated blood levels of C-reactive protein (CRP). CRP is a human serum protein that, when elevated, is an indicator of risk for a variety of diseases, and is a known marker for chronic inflammation. Clinical research has shown that certain forms of coronary artery and vascular diseases, and a number of autoimmune diseases (including diabetes and thyroid disease), all are linked by risk factors that include indications of chronic inflammation. Evidence of reduction in CRP levels in individuals at high risk for these conditions would be strong evidence that RCP-006 can be helpful in the nutritional management of these diseases. Source: PRNewswire 2/28/11

First Patient Treated With Novel Dural Sealant Product Candidate

Kuros Biosurgery AG announced in late February that it has treated the first patient in a pilot clinical trial investigating the safety and efficacy of KUR-023, its novel sealant product candidate for use on the dura mater membrane surrounding the brain and spinal cord. KUR-023 is a synthetic hydrogel-based sealant that utilizes Kuros' synthetic technology. The product candidate is administered as a spray with the aim of ensuring water-tight closure of incisions or tears through the dura mater. It is intended to be used as an adjunct to normal closure techniques such as suturing. The trial is a European, single-arm, multicenter study that will recruit 40 patients. The primary endpoint refers to the prevention of intraoperative leakage with secondary endpoints related to safety and further efficacy assessment. KUR-023 is delivered from a double barrelled syringe with a mixing spray tip. The product candidate is delivered as a spray which then arrives on the dura as a liquid, conforms to the surface, and quickly polymerizes. The applied gel is expected to adhere strongly to the dural surface and be able to withstand cerebral pressures in excess of those experienced in a patient. The gel is designed to be easy to apply, to swell minimally (addressing a common problem with hydrogels), to dissolve over a period of a few months, and not to interfere with the natural healing process. Source: PRNewswire 2/28/11

Company Files European Trial Application for Phase I/II on Lung Cancer Drug Candidate

Helix BioPharma Corp. in February announced that it has filed a clinical trial application with the Central Register of Clinical Trials at the Polish Ministry of Health seeking approval to perform its planned Phase I/II study of its lung cancer drug candidate L-DOS47. L-DOS47 is Helix's first therapeutic immunoconjugate drug candidate under development based upon the company's novel DOS47 technology, which is designed to modify the microenvironmental conditions of cancer cells in a manner that leads to their destruction. L-DOS47 is intended to offer an innovative approach to the first-line treatment of inoperable, locally advanced, recurrent or metastatic, nonsmall cell lung cancer (NSCLC). The proposed study is planned to be an open-label, nonrandomized evaluation of the safety, tolerability, and preliminary efficacy of L-DOS47 alone and in combination with chemotherapy or radiation therapy. The study is planned to be conducted using a multiarm design whereby patients will be recruited into one of four treatment arms: (1) L-DOS47 monotherapy; (2) L-DOS47 + vinorelbine; (3) L-DOS47 + vinorelbine + cisplatin; or (4) L-DOS47 + radiation therapy. Vinorelbine, cisplatin, and radiation therapy are all common treatments used today for NSCLC. The total number of patients to be enrolled in the study will principally depend on the number of patients required to reach the maximum tolerated dose in each treatment arm; however, based on Helix's preclinical studies to date, it currently estimates that the study will enroll approximately 30-to-50 patients in each treatment arm in order to reach this dose. An estimated 20 additional patients are planned to be enrolled per treatment arm for an expanded efficacy evaluation, for a total of 200-to-280 patients. The company estimates that its U.S. Phase I study, already under way, and its planned Polish Phase I/II study will have durations of not less than 12 months and 18 months after commencement of patient enrollment, respectively, followed by analysis and reporting of the study results in each case. Source: Marketwire 2/24/11

Two Phase III Hepatitis B Vaccine Trials Cleared to Continue to Study Completion

Dynavax Technologies Corp. in February announced that the data safety monitoring board established for its two ongoing Phase III trials for its investigational adult hepatitis B vaccine, Heplisav™, has completed its planned safety assessments. The board determined that the studies may continue without protocol modification, and that no other formal meetings of the board are required. The board reviewed safety data from two multicenter trials evaluating Heplisav, the first a lot-to-lot consistency trial in adults 40 years and older, and the second a trial in chronic kidney disease patients. The vaccine candidate is being evaluated with the goal of fulfilling licensure requirements in the U.S., Canada, and Europe. Enrollment has been completed for both studies. In a completed pivotal Phase III trial, Heplisav demonstrated increased, rapid protection with fewer doses than current licensed vaccines; it combines hepatitis B surface antigen with a proprietary Toll-like Receptor 9 agonist known as ISS to enhance the immune response. Source: Marketwire 2/23/11

Phase II Initiated for Pancreatic Cancer Treatment

Infinity Pharmaceuticals, Inc. in February announced the initiation of the randomized Phase II portion of the trial of IPI-926 in combination with gemcitabine (also known as Gemzar®) in patients with previously untreated, metastatic, pancreatic cancer. This portion of the trial is a double-blind study that will compare treatment with IPI-926 in combination with gemcitabine to treatment with placebo and gemcitabine. The primary endpoint is overall survival. Secondary endpoints include progression free survival, time to progression, and overall response rate. The trial is expected to enroll approximately 120 patients worldwide. IPI-926 is a novel, oral molecule that inhibits Smoothened, a key component of the Hedgehog pathway. Inhibition of the Hedgehog pathway represents a fundamentally new approach for addressing a broad range of cancers, including pancreatic cancer. Inhibiting Smoothened with IPI-926 is believed to deplete the dense, fibrous stroma surrounding pancreatic tumors, leading to increased vascularity and facilitating the delivery of chemotherapy to the tumor. Infinity expects to present data from its earlier Phase Ib portion of the trial later this year. Beyond pancreatic cancer, preclinical data suggest that inhibition of the Hedgehog pathway has application across a broad range of difficult-to-treat cancers, and Infinity is planning to begin additional studies with IPI-926 in 2011. Source: Globe Newswire 2/22/11

Emerging Data Encouraging From Proof-of-Concept Trial for Improving Stem Cell Therapy

Fate Therapeutics, Inc. presented encouraging preliminary data from an ongoing Phase Ib clinical trial of FT1050 at the 2011 BMT Tandem Meetings in Honolulu, Hawaii, in February. The goal of the trial is to determine the safety and tolerability of introducing FT1050 during the standard course of dual umbilical cord blood transplant in adult patients with hematologic malignancies, such as leukemia and lymphoma, who have undergone nonmyeloablative conditioning therapy. Fate Therapeutics is developing FT1050 to improve the overall efficiency of hematopoietic stem cell (HSC) support by enhancing HSC homing to and proliferation in the bone marrow. In the ongoing trial, after a reduced-intensity conditioning regimen, each patient receives two umbilical cord blood units for hematopoietic reconstitution: one treated ex vivo at the point-of-care with FT1050 and one untreated. Fifteen subjects of an anticipated 21 have been enrolled to date, with the last six having received an umbilical cord blood unit using the current FT1050 treatment protocol designed to enhance activity; the first nine patients received an umbilical cord blood unit using an earlier version of the FT1050 treatment protocol designed to assess safety. The investigators evaluated the safety of FT1050 as well as the time to initial hematopoietic reconstitution, and which cord blood unit ultimately contributed most to blood count recovery. The average time to engraftment for the six patients who were treated under the current protocol was 18.5 days compared to a historic average of approximately 21 days. In addition, five of these six patients engrafted with the FT1050 treated cord blood unit, suggesting that FT1050 may confer preferential engraftment. In all 15 patients, the safety profile did not appear to differ from that of a standard double umbilical cord transplant. To date, only one patient has experienced Grade 2 or higher acute graft versus host disease. Ten of 15 patients remain alive and disease-free. Accrual is ongoing. The U.S. Food and Drug Administration has granted orphan drug designation to FT1050 for the ex vivo treatment of human allogeneic hematopoietic stem cells to enhance stem cell engraftment by treating neutropenia, thrombocytopenia, lymphopenia, and anemia. The company has also received a positive recommendation by the Committee for Orphan Medicinal Products for orphan designation in the European Union. Source: PRNewswire 2/21/11

Global Phase III Trials Begin in Adults With Chronic Genotype 1 HCV

Tibotec Pharmaceuticals announced in February that two global, registrational Phase III trials are recruiting patients to examine TMC435, its investigational hepatitis C protease inhibitor, in treatment-naive adults with chronic genotype 1 hepatitis C virus (HCV). A third global Phase III trial is being conducted in genotype 1 HCV patients who have experienced a viral relapse after prior interferon-based treatment. The response-guided trials will compare the efficacy, safety, and tolerability of TMC435 given as a single 150 mg oral tablet once daily for 12 weeks versus placebo; each patient also will be treated with a background regimen of peginterferon and ribavirin for 24 or 48 weeks. The first of the double-blind, randomized studies, known as TMC435-C208 or QUEST-1 (QD dosing of TMC435 of previoUsly untreated GEnotype 1 patienTs-1), will evaluate a single TMC435 once-daily oral tablet (150 mg) versus placebo in treatment-naive HCV patients. Both groups will also receive peginterferon alfa-2a (Pegasys®) and ribavirin (Copegus®) as part of their treatment. The second study, known as TMC435-C216 or QUEST-2 (QD dosing of TMC435 of previoUsly untreated GEnotype 1 patienTs-2), also will evaluate a single TMC435 once-daily oral tablet (150 mg) versus placebo in treatment-naive HCV patients; however, patients in this trial will either receive peginterferon alfa-2a (Pegasys) and ribavirin (Copegus) or peginterferon alfa-2b (PegIntron®) and ribavirin (Rebetol®) as part of their treatment. A third study, known as TMC435-C3007 or PROMISE (PROtease inhibitor TMC435 In PatientS who have previously rElapsed on IFN/RBV), will evaluate a single TMC435 once-daily oral tablet (150 mg) verses placebo in HCV patients who experienced viral relapse after previous interferon-based therapy. Both groups will receive peginterferon alfa-2a (Pegasys) and ribavirin (Copegus). The complete treatment duration for all three trials will be 24 or 48 weeks, depending on patient response. The studies will be conducted at more than 160 sites in 24 countries, including the U.S. and countries throughout Europe, and together seek to enroll approximately 1,125 HCV genotype 1 infected patients who are treatment-naive or have experienced a relapse after previous interferon-based HCV therapy. The primary endpoint of the studies is to assess whether TMC435 is superior to placebo in achieving sustained virologic response (SVR), defined as HCV RNA <25 IU/ml undetectable, 24 weeks after the planned end of treatment (SVR 24), with the final analysis being performed after the last patient reaches week 72 of the study. Secondary endpoints include superiority of TMC435 versus placebo at 12 weeks (SVR 12), after planned end of treatment and at week 72 of the study. Evaluations of viral breakthroughs, relapse rates in treatment groups, safety, and tolerability also will be assessed. Phase III studies for TMC435 also recently launched in Japan. Source: PRNewswire 2/18/11

Foundation Launches First Trial of Drug-Free Infrared Light Therapy to Treat Dementia

Quietmind Foundation, a nonprofit clinical research, consultation, and training organization, is launching the first-ever clinical trial of its type to assess a new approach to improve mental functioning for sufferers of early-stage dementia. The study measures whether problems with executive functioning (including attention, working memory, strategies of learning and remembering, planning, organizing, self-monitoring, inhibition, and flexible thinking) can be positively influenced by repeated brief exposures to 1072nm infrared light stimulation to increase cerebral blood flow (CBF) and oxygenation. Early results from testing the technology in the United Kingdom have been encouraging. "We have seen strong early evidence that infrared light stimulation can help dementia patients regain lost ground," notes Marvin H. Berman, PhD, who heads the foundation. "This approach also represents a new direction for those seeking nonpharmacological treatment for themselves or their loved ones." This randomized, controlled, double-blind study requires that applicants be between the ages of 50 and 85 and previously diagnosed with early-stage dementia. Participants go through several initial steps, including an evaluation of cognitive functioning, a specialized electroencephalographic (EEG) recording of brain activity, and pen and paper cognitive testing. In addition, the study requires a 28-day commitment. Those selected are randomly assigned to receive either an active treatment or a placebo treatment daily for 28 consecutive days. The initial trial will be conducted at the foundation's offices in Plymouth Meeting, Pa., or select area locations. Other locations will be considered based on expressed interest. Source: Marketwire 2/17/11

First Patient Enrolled in Second Phase III Trial of Bladder Cancer Treatment

Endo Pharmaceuticals and Bioniche Life Sciences Inc. in February announced enrollment of the first patient in the second Phase III clinical trial of Urocidin™. The trial is a randomized, active-controlled, open-label, multicenter study with a blinded endpoint assessment designed to compare Urocidin with mitomycin C in the intravesical treatment of patients with BCG recurrent or refractory non-muscle-invasive bladder cancer. It is estimated that 450 patients will be enrolled for this new trial at approximately 120 clinical sites worldwide. Non-muscle-invasive bladder cancer is a form of bladder cancer localized in the surface layers of the bladder that has not yet spread into the deeper muscle layer. This form of bladder cancer is treated predominantly by urologists using surgical resection and intravesical infusion therapy. Urocidin is an intravesical infusion therapy, administered via transurethral catheter into the bladder. It is a formulation of MCC, a sterile mycobacterial cell wall-DNA complex composition that has a dual mode of action: immune stimulation and direct anticancer activity. Source: PRNewswire 2/16/11

Phase I Trial Initiated in Patients With Solid Tumors

Genus Oncology, LLC announced it has successfully filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) and has dosed the first patient in a Phase I trial to test its lead compound, GO-203-2c, in patients with solid tumors. The company says its work demonstrates that Mucin 1 (MUC1) is a viable drug target, and that inhibition of MUC1 function blocks tumor development and survival of multiple human cancers in preclinical models, including breast, prostate, colon, lung, and pancreatic cancers. The trial is a prospective, open-label study that is designed to determine the safety, tolerability, and potential antitumor activity of GO-203-2c. Up to 40 patients will be enrolled in the study at multiple clinical sites. The sites currently contracted to conduct the trial are the University of Texas Health Science Center at San Antonio and the Virginia G. Piper Cancer Center at Scottsdale Healthcare Hospital. Additional sites are currently under consideration. In normal cells, MUC1 coats the intestine and other organs and prevents penetration of bacteria and other pathogens. The MUC1 protein is abnormal and present in high concentrations in cancer cells and appears to be important in cancer cell growth; GO-203-2c is one of the first peptides to specifically target this molecule. To date, there are no approved agents that target MUC1. Source: PRNewswire 2/15/11

Phase III Completed for Treatment of Postmenopausal Osteoporosis; Phase II Prevention Trial Begins

Tarsa Therapeutics, Inc. in February announced completion of its global Phase III ORACAL trial testing the company's once-daily oral recombinant calcitonin for the treatment of postmenopausal osteoporosis. Results from the trial are expected in early spring. In addition, Tarsa announced initiation of a new Phase II study of the drug for the prevention of postmenopausal osteoporosis. The ORACAL study is a multinational, randomized, double-blind, active and placebo-controlled trial that enrolled 565 postmenopausal women with osteoporosis. Analysis of the trial data is currently under way. The new prevention trial is a randomized, double-blind, placebo-controlled study designed to enroll approximately 120 postmenopausal women with low bone mass at increased risk of fracture; it will explore the optimal dosing regimen for oral calcitonin by administering the tablets either with the evening meal or at bedtime. The trial will assess the efficacy of Tarsa's oral calcitonin in the prevention of bone loss in these women, as well as its safety and tolerability. The prevention trial is being conducted at multiple centers in the U.S. Tarsa plans to submit a New Drug Application to the U.S. Food and Drug Administration for the use of its oral calcitonin as a treatment for postmenopausal osteoporosis later this year, and a Marketing Authorization Application to the European Medicines Agency next year. Calcitonin is currently approved for the treatment of postmenopausal osteoporosis, but its use has been limited by the fact that it is currently available only in intranasal and injectable forms. Source: PRNewswire 2/14/11

Trial of ACL Reconstruction Device Under Way

Aperion Biologics, Inc. has announced the enrollment and implantation of the first patients in the company's clinical trial of its Z-Lig™ anterior cruciate ligament (ACL) reconstruction device for the treatment of ligament injuries of the knee. The primary objective of the multicenter study is to provide additional evidence of the safety and performance of Z-Lig in the reconstruction of patients' knees with primary ACL ruptures. Seven sites in Europe and one site in South Africa are participating in this clinical trial. The study results will be used to support regulatory approvals and clinical acceptance of Z-Lig in select markets outside the United States. The product represents an opportunity to provide a biologic graft sourced from nonhuman tissue. This device is a functional scaffold that supports the regeneration of the patient's own tissue by way of a proprietary immunochemically modified porcine tissue. Z-Lig is the only known biological alternative to human tissue for ACL replacement in clinical evaluation. Since Z-Lig is a biological implant that maintains a mechanically stable scaffold, it can become populated and remodeled with the patient's own cells (similar to human-sourced tissue). Aperion previously completed a clinical study for Z-Lig in the U.S. in which the grafts successfully demonstrated safety and feasibility during the two-year evaluation. Source: PRNewswire 2/11/11

Company Updates ALS Clinical Trial Progress

Neuralstem, Inc. has updated the progress of its ongoing Phase I human clinical trial of the company's spinal cord stem cells in the treatment of 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 nine patients, the trial's safety monitoring board has unanimously approved moving to the last group of ALS patients in this part of the safety trial. These next three patients, all of whom are ambulatory, will each receive 10 injections, bilaterally, in the lumbar spinal cord. After this cohort, the Food and Drug Administration (FDA) will review the trial data to date before approving it to move into the final cohort of patients. The Phase I trial to evaluate the safety of Neuralstem's spinal cord stem cells in the treatment of ALS, the first FDA-approved ALS stem cell trial, has been under way since January 2010. The trial plans to enroll up to 18 ALS patients, who will be examined at regular intervals postsurgery. All of the first six patients treated in the trial were nonambulatory. Of these, the first three received five injections each, unilaterally, in the lumbar region of the spinal cord. The next three patients received 10 injections each, bilaterally, in the lumbar region. All remaining trial patients are ambulatory, and therefore represent earlier stages of disease progression. Of the ambulatory group, the first three patients received five injections each, unilaterally, in the lumbar region. After the required FDA approval, the final six patients in the trial will receive injections in the cervical region. While the trial is evaluating only the safety of the cells and procedure, it includes exploratory endpoints including attenuation of motor function loss, maintenance of respiratory capacity, and stabilization of patients along the ALS functional rating scale. The Emory ALS Center has posted the relevant trial information for patients on its website here. Source: EurekAlert! 2/10/11

CRO Expands Clinical Trials Services Team in India, Adds Strategist for Pediatric Studies

The North Carolina-based contract research organization (CRO) INC Research, LLC recently appointed an executive director for global services/site head and a senior manager for clinical operations to help manage its clinical trial efforts in India. They join the recently appointed senior medical director for medical affairs in that country. "India has continued to be a key region for our customers' overall drug development strategies. We have been building the right team with the right set of clinical trials services to meet the specific needs in the country," said Kelvin Logan, PhD, president of INC Research Europe and Asia Pacific. INC Research provides Phase I through IV global clinical trial services for India based out of its Gurgaon office in a fast-growing business district on the outskirts of Delhi. The India operations also serve as a hub for the company's contracts and functional services group and data management, data entry, and clinical programming groups. Source: Marketwire 2/10/11 In other news, INC Research has appointed a new principal strategist for developing the company's operational strategy and providing expertise in the design and execution of pediatric studies for neonates, infants, children, and adolescents. Source: Marketwire 2/3/11

Final Data Show Experimental Agent Better Than Aspirin at Preventing Stroke

A new anticlotting agent is vastly superior to aspirin at reducing stroke risk (1.6 percent per year versus 3.6 percent per year) in atrial fibrillation (AF) patients unable to take stronger drugs, according to final data reported at the American Stroke Association's International Stroke Conference 2011. Researchers found the drug also works better in people with a history of stroke or a warning stroke. The AVERROES: Apixaban Versus Acetylsalicylic Acid (ASA) to Prevent Strokes trial is a randomized trial of 5,600 AF patients at moderate to high risk of stroke who were not willing or able to take oral vitamin-K antagonists like warfarin, a drug commonly prescribed to prevent blood clots in people with AF. They were treated at 520 medical centers worldwide. A May 2010 interim analysis found evidence that the investigational oral drug apixaban was so much more superior to aspirin that the researchers were advised to end the trial early. The drug blocks factor Xa, a crucial step in blood clot formation. It had been expected that a more powerful drug like apixaban would be associated with more severe bleeding complications compared to aspirin, but it wasn't. The study's primary endpoint was the reduction of ischemic stroke, hemorrhagic stroke, and systemic embolism. The primary safety endpoint was major bleeding incidents. Patients were randomized to receive either apixaban at 5 mg twice a day (2.5 mg twice a day in selected patients) or between 81 mg and 324 mg of aspirin per day. The study's double-dummy design mandated that patients randomized to receive apixaban took an aspirin-placebo and those randomized to receive aspirin got an apixaban-placebo, he explained. During an average of 1.1 years of follow up, the researchers found 51 strokes or systemic embolism events in the 2,808 patients taking apixaban compared to 113 strokes and systemic embolic events in the 2,791 patients taking aspirin, meaning apixaban carries about half the relative risk of stroke or systemic embolism compared to aspirin. Although bleeding events were slightly higher with apixaban, the difference fell short of statistical significance. Bristol-Myers Squibb and Pfizer funded the study. Source: EurekAlert! 2/10/11

Phase II Trial Evaluating Drug Coadministered with Enzyme Replacement Therapy

Amicus Therapeutics in February announced the dosing of the first subject in a Phase II clinical trial designed to evaluate the coadministration of its investigational drug Amigal™ (migalastat hydrochloride) with enzyme replacement therapy (ERT) for Fabry disease. This open-label is investigating drug-drug interactions between Amigal and the ERTs Fabrazyme® and Replagal®. Preclinical studies have demonstrated that coadministration of Amigal results in a prolonged circulating half-life of ERT, increased enzyme activity in cells, and greater substrate reduction in target tissues compared to that seen with ERT alone. Amigal is being developed in collaboration with GlaxoSmithKline. The trial will evaluate safety and pharmacokinetics in 18 male patients with Fabry disease, ages 18-65, who have been receiving ERT for at least one month before study entry. Each patient will receive ERT alone and then ERT after administration of a single oral dose of Amigal. There will be two cohorts of nine patients treated with one of two Amigal dose levels. The primary outcome measure will be a comparison of the ERT activity in plasma and safety and tolerance with and without coadministration of Amigal. The effect of coadministration of ERT on the pharmacokinetics and safety of Amigal will also be evaluated. A secondary outcome measure includes distribution of the ERT to skin. Other outcome measures include evaluating the effect of coadministration of Amigal and ERT on GL-3 levels in skin and GL-3 excretion in urine. Amicus expects results from this study to be available in the second half of 2011. Approximately five clinical sites will participate in this trial in the United States and in Europe. Source: PRNewswire 2/9/11

Company Receives Clearance to Initiate Trial for Influenza Vaccine Candidate

Medicago Inc. in February announced it has received Food and Drug Administration (FDA) clearance for its Phase I H1N1 influenza VLP vaccine candidate clinical trial in the United States. The company plans to initiate this trial within the coming weeks; it will lead into Medicago's U.S. Phase IIa trial for its seasonal trivalent vaccine with the recommended H1N1, H3N2, and B influenza strains, which the company plans to conduct later in 2011. The randomized, double-blind, multicenter, active- and placebo-controlled dose-ranging study will evaluate the safety, tolerability, and immunogenicity of a single nonadjuvanted dose of the H1N1 vaccine in 100 healthy adults 18-49 years of age. The subjects will be randomized to receive either an injection of a placebo, Medicago's H1N1 vaccine, or an H1N1 vaccine from a licensed trivalent vaccine. The primary safety and immunogenicity results are expected within three months of the start of this study. These data will support the development of the company's seasonal influenza VLP vaccine in the United States. Source: PRNewswire 2/8/11

Trial Under Way with New Antitumor Product

PharmaMar SA has announced the commencement of a Phase I clinical trial with PM060184 for patients with solid tumors. PM060184 is a marine-derived, synthetically produced compound that has shown strong in vitro and in vivo antitumor activity and a favorable safety profile in preclinical toxicology studies. PM060184 is PharmaMar's sixth compound in clinical development. The trials will be performed in hospitals in the U.S., France, and Spain. The primary endpoints of this trial are to identify the dose-limiting toxicity, the maximum tolerated dose, and the recommended dose of PM060184. Additionally, the drug's pharmacokinetic profile will be defined and a preliminary evaluation of its antitumor activity in patients will be performed. Source: PRNewswire 2/7/11

Treatment Yields Positive Results for Skin Appearance Improvements

Photocure in early February announced positive results from its consumer trial with Allumera™, a topical cosmetic treatment formulated to improve the skin's appearance. The RevitAll study was performed with a standard cosmetic protocol and designed to confirm if treatment with Allumera improves skin appearance when compared to exposure by light alone. The study also looked into longevity of results. This controlled, prospective study enrolled 120 women to receive three treatments, four weeks apart, for five months. Half the study participants received Allumera plus light, while the remaining received light alone (control group). Participants were monitored for three months following the last treatment to evaluate which effects were long-lasting. The study evaluations included both objective and subjective assessments. The objective assessments included measurement of pores, skin firmness/elasticity, skin tone (radiance/luminosity), skin surface topography, and tolerability. At the five-month evaluation, participants who received Allumera for one hour followed by exposure to light showed a 44 percent reduction in the appearance of pores when compared to baseline, and the difference between the two groups was statistically significant (p=0.002). A statistically significant improvement (p<0.0001) in skin firmness and suppleness was also observed for the Allumera group when compared to the control group. A 35 percent improvement in the appearance of skin tone (p<0.05) was also found, but this was not statistically significant when compared to the control group. In addition to the objective statistical measurements, Allumera demonstrated significant subjective feedback from trial participants including confirmation of revitalized, younger-looking, clearer, and more beautiful skin; reduced appearance of crows feet, dark circles, fine lines, and wrinkles; firmer appearance of skin; and improvement in the feeling of moisture, smoothness, and overall skin texture. Due to positive clinical trials with Allumera treatment on facial skin, the product is currently being studied on other cosmetically important areas, such as the hands, neck, chest, arms, and legs. Source: PRNewswire 2/4/11

Company Signs Contract to Initiate Phase II Cognitive Impairment Trials in Europe

Neurokine Pharmaceuticals Inc. announced that it has signed a contract with Clinical Investigations Group (CIG) in the United Kingdom to conduct Phase II clinical trials to study the effects of NK-001 in protecting patients against cognitive impairment (Alzheimer's-type) side effects of coronary artery bypass graft surgery. CIG will conduct these trials in 50 patients at three centers in Europe. The company will immediately begin to collaborate with CGI to complete all necessary documentation for submission of approval of its protocol for clinical trials in Europe. Source: Marketwire 2/3/11

Milestone Studies Announced for COPD Treatments

GlaxoSmithKline and Theravance, Inc. in early February announced milestones in two clinical development programs focused on new treatments for patients with chronic obstructive pulmonary disease (COPD). The first is the initiation of the 52-week, randomized Phase III program for the once-daily LAMA/LABA dual bronchodilator GSK573719/vilanterol ('719/VI), which will evaluate more than 5,000 patients globally. Patients are now being enrolled in a large safety study, which will be followed shortly by four large pivotal studies that will compare improvements in lung function between '719/VI, its components, placebo, and tiotropium. The program will also include two further studies assessing the effect of '719/VI on exercise endurance. The second milestone is the start of a four-arm, randomized, double-blind, parallel-group outcomes study of 16,000 patients across 1,100 global sites to assess the potential for Relovair™ to improve survival in those with COPD and a history of, or at risk from, cardiovascular disease. Relovair is a once-daily inhaled corticosteroid/LABA combination treatment, already under Phase III development with approximately 6,000 patients across five pivotal registration studies, comprising fluticasone furoate and vilanterol. Source: Marketwire 2/3/11

Enrollment Halted in Phase III Lung Cancer Trial

Eli Lilly and Co. and Bristol-Myers Squibb Co. announced in early February that they have stopped enrollment in one of their two global Phase III studies evaluating necitumumab, an investigational anti-cancer agent, as a first-line treatment for advanced non-small cell lung cancer (NSCLC). The randomized, multicenter, open-label Phase III trial, named INSPIRE, is evaluating the addition of necitumumab, a fully-human IgG1 monoclonal antibody, to a combination of Alimta® (pemetrexed for injection) and cisplatin compared to a regimen of Alimta and cisplatin, as a first-line treatment for patients with advanced nonsquamous NSCLC. No new safety issues were seen in the control arm with Alimta and cisplatin. The decision to stop enrollment followed an independent data monitoring committee recommendation that no new or recently enrolled patients continue treatment in the trial because of safety concerns related to thromboembolism (blood clots) in the experimental arm of the study. The committee also noted that patients who have already received two or more cycles of necitumumab appear to have a lower ongoing risk for these safety concerns. These patients may choose to remain on the trial, after being informed of the additional potential risks. Investigators will continue to assess patients after two cycles to determine if there is a potential benefit from treatment. Necitumumab continues to be studied in a Phase III trial named SQUIRE. This study is evaluating necitumumab as a potential treatment for a different type of lung cancer called squamous non-small cell lung cancer in combination with Gemzar® (gemcitabine HCl for injection) and cisplatin. The same independent committee recommended that this trial continue because no safety concerns have been observed. Lilly has contacted all trial investigators to provide detailed information on how to manage individuals enrolled in the trial, and has notified all pertinent regulatory agencies of this decision. Source: PRNewswire 2/2/11

T-cell Vaccine Reduces Allergy Symptoms in Phase II

Circassia Ltd in February announced that the company's ToleroMune® cat allergy treatment significantly reduced patients' symptoms in a recently completed, large-scale Phase II clinical trial. The study also confirmed the treatment's highly favorable safety profile. The study was the first to use the company's commercial room-temperature-stable formulation, and provides confirmatory proof-of-concept for the final stage of development of its cat allergy T-cell vaccine. Circassia conducted the double-blind study in Toronto, Canada, where investigators randomized 202 cat allergy patients to receive either four or eight standardized doses of ToleroMune treatment or placebo. To determine the effect of the therapy, the volunteers systematically recorded their nasal and ocular allergy symptoms, both before and after treatment, while exposed to aerosolized cat allergens in a validated environmental exposure chamber. The study results show that the ToleroMune T-cell vaccine had an immediate and growing treatment effect as allergen exposure increased. The key patient group, which received four doses of the T-cell vaccine over a period of 12 weeks, had significantly reduced levels of allergy symptoms when compared to placebo. These patients experienced a 55 percent greater improvement in their symptoms despite a larger than anticipated placebo effect. Circassia is currently conducting a 12-month follow-up study to determine the duration of the treatment effect, with results anticipated in the second half of 2011. Source: PRNewsire 2/1/11

Phase II Study Will Evaluate Leukemia DNA Vaccine Delivery Technology

Inovio Pharmaceuticals, Inc. in late January announced the regulatory approval of a Phase II clinical trial (WIN Trial) to treat leukemia utilizing Inovio's new ELGEN 1000 automated vaccine delivery device. This open-label, multicenter clinical trial being run by the University of Southampton is evaluating a DNA vaccine to treat chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Financial support for the trial is being provided by the U.K. research charity Leukaemia and Lymphoma Research and by the Efficacy and Mechanisms Evaluation program. The DNA vaccine was developed at the University of Southampton with funding from LLR and the charity Cancer Research U.K. Wilms' Tumor gene 1 (WT1) is highly associated with these types of cancer, which led the University of Southampton to design its leukemia DNA vaccine to target this antigen. This will be the first study to combine DNA vaccination with electroporation delivery of WT1 antigens with the goal of stimulating high and durable levels of immune responses, critical for improving clinical outcomes. The single-dose level study is designed to recruit two patient groups. One group is planned to recruit up to 37 CML patients and the other up to 37 AML patients. All participants will initially receive six doses of two DNA vaccines (called p.DOM-WT1-37 and p.DOM-WT1-126) delivered at four-week intervals. Vaccine responders may continue with booster vaccinations every three months out to 24 months. An additional 100 to 110 AML/CML patients will be enrolled across the two arms as nonvaccinated controls for comparison. The primary endpoints will be molecular response to a disease marker called BCR-ABL in CML patients and time to disease progression in AML patients. The study will also monitor WT1 transcript levels, immune responses to the WT1 antigen, time to progression and overall survival, and two-year survival in the AML group. The trial will take place at hospitals in Southampton, London and Exeter over the next two years. Regulatory approval to start this clinical study was provided by the U.K. Medicines and Healthcare Products Regulatory Authority and Gene Technology Advisory Committee. The ELGEN 1000 device's needle electrodes automate vaccine delivery at the push of a button and co-locate subsequent controlled, millisecond electrical pulses that increase cell membrane permeability and improve cellular uptake of the vaccine. Inovio's electroporation systems have been shown to increase levels of gene expression (production of the antigen coded by the DNA vaccine) up to 1,000-fold and increase immune responses to the antigen up to 100-fold. Source: PRNewswire 1/31/11

Company Receives FDA Approval to Move Forward with Critical Limb Ischemia Trial

Arteriocyte® in late January announced approval from the Food and Drug Administration (FDA) to initiate a Phase I clinical trial using its Magellan MAR01™ technology in the treatment of critical limb ischemia (CLI). The FDA Investigational Device Exemption (IDE 14522) allows Arteriocyte and its clinical partners to initiate evaluation of concentrated marrow injections (using the Magellan MAR01 technology) in improving perfusion in ischemic tissue in affected limbs of patients with CLI who are not eligible for revascularization surgery. The Magellan technology combines a rapid bedside tissue concentration device and sterile surgical disposables that produce platelet-rich plasma from blood and bone marrow aspirations in approximately 15 minutes; it was approved by the FDA through the 510(k) process for use as deemed appropriate by surgeons to achieve rapid "closed system" concentration of aspirated bone marrow, yielding an injectable tissue rich in platelets, hematopoietic stem cells, and mesenchymal stem cells, commonly viewed as key components in tissue repair. The company is developing MAR01 for use as in CLI treatment, and plans to initiate additional clinical trials evaluating MAR01 in cardiovascular disease, orthopedics, and tissue repair during 2011. Patient enrollment for the Phase I safety study will begin immediately at the Ohio State University Medical Center, as the first clinical site. Source: PRNewswire 1/28/11

Top-Line Results Falter in Phase III Study in Metastatic Triple-Negative Breast Cancer

Sanofi-aventis and its subsidiary, BiPar Sciences, in late January announced that a randomized Phase III trial evaluating iniparib (BSI-201) in patients with metastatic triple-negative breast cancer (mTNBC) did not meet the prespecified criteria for significance for coprimary endpoints of overall survival and progression-free survival. Importantly, the results of a prespecified analysis in patients treated in the second- and third-line setting demonstrate an improvement in overall survival and progression-free survival, consistent with what was seen in the Phase II study. The overall safety analysis indicates that the addition of iniparib (BSI-201) did not significantly add to the toxicity profile of gemcitabine and carboplatin. "While this trial did not meet its primary goal, we believe that the improvement in overall survival and progression-free survival in patients in the second- and third-line setting are important findings," said Dr. Debasish Roychowdhury, senior vice president and head oncology for sanofi-aventis. "We are conducting in-depth analysis to gain further insight into these Phase III results. Sanofi-aventis remains committed to improving outcomes for patients with triple-negative breast cancer where there is high unmet medical need." Sanofi-aventis plans to discuss these data with United States and European health authorities in the near future. Full study results will be presented at an upcoming major oncology conference. The current clinical development program for iniparib continues in breast, lung, and other cancers. The study enrolled 519 women with mTNBC from 109 sites in the United States. Patients were randomized to receive a standard chemotherapy regimen (gemcitabine and carboplatin) on days one and eight of each 21-day cycle, with or without iniparib 5.6 mg/kg, which was administered on days one, four, eight, and 11 of each 21-day cycle. Patients in the study had received up to two previous lines of chemotherapy in a metastatic setting. Source: PRNewswire 1/27/11

Update Provided on Company's Initial Cancer Target

PharmaGap Inc. has provided guidance to stakeholders on its progress toward clinical trials involving its GAP-107B8 drug. Through the first half of 2011, PharmaGap's clinical development program is focused on testing and development activities in order to provide the company with the basis for selection of the initial cancer target for clinical trials. This decision will be based test results obtained against specific cancer targets using GAP-107B8 and variants, and the observed behavior of the drug using the different routes of administration commonly found in the clinic for the cancer indications under investigation; the absence of or deficiencies in current standard of care; and any accelerated approval programs available for the selected cancer type. Tests to date have shown efficacy in treatment of a range of cancers. Bladder cancers using intravesical administration and ovarian cancers using intraperitoneal administration are being assessed as potential first candidates for clinical trials. Both routes of administration are recognized as viable clinical delivery methods for the applicable cancer type. PharmaGap's prime objective in the first half of this year is to select the single cancer target and clinical formulation of GAP-107B8 that will provide the company with the best opportunity for successful completion of all regulatory requirements to be met in order to commence clinical trials in the first half of 2012. Key activities under way to support this decision include in vitro and in vivo testing of GAP-107B8 at collaborator sites previously announced, as well as a range of in vitro testing at PharmaGap characterizing candidate dosage forms intended for use in in vivo tumor model studies and subsequent human trials. Bioanalytical, pharmacokinetic, and toxicology profiling for both intraperitoneal (for ovarian) and intravesical (for bladder) delivery systems has commenced and will be ongoing through the first half of 2011, both internally and at contract research organizations. Formulation work, which is under way, includes investigation into the effect of excipients to the core active pharmaceutical ingredient that is central to GAP-107B8's activity, as well as to investigation and development of the final dosage form of product for use in humans. Source: Marketwire 1/27/11

Positive Phase IV Results Seen from Treatment for Shift Work Disorder

Cephalon, Inc. in January announced positive results from a Phase IV clinical trial of Nuvigil® (armodafinil) tablets in patients experiencing excessive sleepiness associated with shift work disorder, specifically during the end of their night shifts, including the commute home. The study data showed statistically significant difference in improvement in overall clinical condition related to late-shift sleepiness in patients receiving Nuvigil compared to the placebo group. This is the largest trial ever conducted in this patient population, with more than 380 patients randomized to treatment with the drug or placebo. The primary outcome measure of this six-week, multicenter, double-blind study of Nuvigil (150 mg) was the Clinical Global Impression of Change scale, with which the clinician rated a patient's improvement in overall clinical condition as it related to sleepiness with shift work disorder late in the shift. Using this rating, the percentage of patients taking Nuvigil who experienced improvement from baseline was 77 percent versus 57 percent for placebo. The key secondary outcome was measured using the Global Assessment of Functioning, with patients receiving Nuvigil showing a 9.5 point improvement over baseline versus a 5.2 point improvement in the placebo group. The first presentation of these data will occur during the Society of General Internal Medicine's 34th Annual Meeting in May. Additional results also will be submitted for future publications and presented at medical meetings. Source: PRNewswire 1/25/11

IVF Device Trial Begins in Brazil

INVO Bioscience, Inc. in January announced the commencement of a 40-patient clinical trial in Rio de Janeiro, Brazil to establish safety, efficacy, and comparative in vitro fertilization (IVF) measures of the INVOcell device. The design for the trial has been submitted for approval to the Federal Ethics Committee in Brazil. Upon approval of the trial design, results from the completed clinical study will be submitted to the National Health Surveillance Agency (ANVISA) for the purpose of gaining registration and approval for the sale of the INVOcell device in Brazil. The INVOcell is a Class II device in Brazil, which requires clinical data obtained in Brazil for submission, registration, and approval of the device by ANVISA. This trial is being sponsored and conducted by Dr. Francisco Augusto Colucci Coelho of the Center of Infertility and Fetal Medicine of North Rio de Janeiro. The first trial patient has been treated utilizing the INVOcell device and procedure. An ultrasound exam performed eight weeks after the INVO procedure detected a fetal heart beat confirming a clinical pregnancy. Enrollment for the remainder of the trial population is expected to be completed within four months. Final results of the trial, along with the recently announced clinical trial results from Dr. Elkin Lucena of the Colombian Fertility and Sterility Center in Colombia, South America, will be submitted to ANVISA for registration and approval. According to the company, the INVOcell device and procedure feature the processing of significantly fewer eggs from patients, reducing the occurrence of multiple pregnancies and the attendant costs and complications; relative cost advantages compared to traditional IVF treatments; and pregnancy rates that are comparable to traditional IVF treatments. INVOcell is CE Mark approved in Europe and Canada, and is currently marketed and sold in Austria, Bolivia, Cameroon, Columbia, the Dominican Republic, Guatemala, Nicaragua, Pakistan, Panama, Peru, Spain, Togo, Turkey, and Venezuela. Additionally, the company has commenced registration processes in China, and now Brazil, while continuing to explore additional appropriate countries to begin the registration process to market its products. Source: PRNewswire 1/25/11

Phase IIa Study Completed for Androgenetic Alopecia Treatment

R-Tech Ueno, Ltd. in January announced that its Phase IIa clinical study of RK-023 had been completed in 48 patients with mild-to-moderate androgenetic alopecia to evaluate the safety, pharmacokinetics, and efficacy of doses applied repeatedly for 13 weeks. The double-masked, randomized, and placebo-controlled involved the application of 2 mL of RK-023 to a hair-thinning part of scalp twice daily. Laboratory tests, vital signs (blood pressure, pulse rate, body temperature, and respiratory rate) and electrocardiogram were examined as the safety assessment. Concentrations of RK-023 and its main metabolite in plasma were determined as a pharmacokinetic study. Dermatologic examination for the degree of baldness, global photo assessment, subject self-assessment, and phototrichogram were examined as the efficacy assessment. Subjects receiving RK-023 showed possibility of improvement in global photo assessment and in numbers of anagen hair from the baseline compared to those in the placebo group. Source: PRNewswire 1/24/11

Phase II Enrollment Resumes for Brain Cancer Trial

In January, Northwest Biotherapeutics announced it was resuming enrollment for its ongoing 240-patient, double-blind, randomized, placebo-controlled Phase II clinical trial of DCVax for glioblastoma multiforme (GBM) brain cancer. Due to financial concerns in 2008, the company stopped enrollment, with 33 patients who had already been enrolled continuing to be treated with the cancer vaccine. "We never suspended the trial," explained Chairman of the Board Linda Powers. "We found and spent the money to keep the trial open and we kept treating those who had already enrolled. During the worst of this Great Recession, we did preserve our resources by not enrolling any new patients on top of the couple dozen patients already enrolled and being treated at our 13 trial sites across the country, in anticipation of continuing our positive clinical results and a broader economic revival. ...Our goal [now] is to move as quickly as possible toward commercialization of this easily administered, promising brain cancer vaccine for all of these patients, at a cost well below chemotherapy and other competitive vaccines. We can reach that goal by completing this clinical trial as quickly as possible, and confirming the clinical benefits of DCVax, as seen in our prior clinical trials, in delaying recurrence of patients' tumors and extending patients' survival." Source: Marketwire 1/24/11

Company Initiates Phase I/II Trial in Pompe Disease

BioMarin Pharmaceutical Inc. announced in January that it has initiated a Phase I/II trial for BMN 701, a novel fusion protein of insulin-like growth factor 2 and acid alpha glucosidase (IGF2-GAA) in development for the treatment of Pompe disease. "We have a strong track record of quickly developing enzyme replacement therapies for unmet medical needs and expect to leverage our clinical and regulatory experience and manufacturing know-how in the development of BMN 701," said Jean-Jacques Bienaime, chief executive officer of BioMarin. "There is a significant amount of interest in the medical community for a more effective treatment option for late-onset Pompe disease, and we believe, based on in vitro and in vivo nonclinical studies, that using our proprietary Glycosylation Independent Lysosomal Targeting, or GILT technology, BMN 701 has the potential to deliver more enzyme to lysosomes compared to traditional mannose-6-phosphate targeted approaches." The trial is an open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamic, and clinical activity of BMN 701 administered as an intravenous infusion every two weeks at doses of 5 mg/kg, 10 mg/kg, and 20 mg/kg. The company expects to enroll approximately 30 patients between the ages of 13 and 65 with late-onset Pompe disease for a treatment period of 24 weeks. Source: PRNewswire 1/19/11

Company Announces Randomized Phase II Pancreatic Cancer Study

Oncolytics Biotech Inc. announced in January that the Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, U.S. National Cancer Institute (NCI), which is part of the National Institutes of Health, has agreed to sponsor a two-arm, randomized Phase II study of carboplatin, paclitaxel, and Reolysin® versus carboplatin and paclitaxel alone in the first-line treatment of patients with recurrent or metastatic pancreatic cancer. The NCI is sponsoring the trial under its Clinical Trials Agreement with Oncolytics, while Oncolytics will provide clinical supplies of Reolysin. The study is an open-label, multi-institution study in which patients in both arms will receive treatment every three weeks (21-day cycles). Patients in both arms will receive standard intravenous doses of paclitaxel and carboplatin on day one only. In Arm A, patients will also receive intravenous Reolysin on days one through five. Tumor response assessment will be done by CT scan and conducted every eight weeks. Patients that progress on carboplatin and paclitaxel (Arm B) will have Reolysin added. If patients experience significant toxicity related to carboplatin and/or paclitaxel, they may continue with single agent Reolysin. The primary objective of the trial is to assess improvement in progression-free survival with Reolysin, carboplatin, and paclitaxel relative to carboplatin and paclitaxel alone. The primary endpoint is progression-free survival in both arms. Secondary endpoints include overall response rate and overall survival. The study is expected to enroll approximately 70 patients. This is the fourth clinical trial using Reolysin to be sponsored by the NCI. The NCI is currently conducting a Phase II metastatic melanoma trial, a Phase I/II ovarian, peritoneal, and fallopian tube cancer trial, and has announced its intention to sponsor a randomized Phase II trial in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer. Source: PRNewswire 1/18/11

More Data Released on Analgesic for Post-Bunionectomy Pain

Pacira Pharmaceuticals, Inc. in January announced that new data from its Phase III bunionectomy study to evaluate the efficacy and safety of the intraoperative administration of Exparel™ (bupivacaine extended-release liposome injection) was presented in a poster session at the 57th Annual Meeting of the Orthopaedic Research Society in Long Beach, Calif. Study results from this multicenter, randomized, double-blind, parallel-group, placebo-controlled bunionectomy trial demonstrate that the median time to first use of opioid rescue medication was 7.2 hours for patients treated with Exparel compared to 4.3 hours for patients treated with placebo. The trial studied 193 subjects in four U.S. centers to determine the safety and efficacy of a single administration of Exparel for prolonged postoperative analgesia in subjects undergoing first metatarsal osteotomy (bunionectomy). Previously disclosed Phase III findings in this study showed Exparel met its primary endpoint, with a statistically significant reduction in area under the curve analysis of the pain intensity numeric rating scale scores in subjects receiving Exparel compared to placebo over the first 24 hours following surgery. Source: PRNewswire 1/13/11

Phase III Study of Crohn's Disease Treatment Initiated

GlaxoSmithKline and ChemoCentryx, Inc. announced in January that treatment of the first patient with Crohn's disease has been initiated in the initial pivotal induction study comparing Traficet-EN, now designated GSK1605786 ('786), to placebo. This marks the start of the Phase III clinical development programme for '786 for the treatment of this serious and chronic disease. '786 is a nonbiologic, orally bioavailable antagonist of CCR9, a chemokine receptor that plays a central role in the inappropriate inflammatory response thought to underlie Crohn's disease. The programme is anticipated to include another pivotal induction study and a pivotal maintenance study, in addition to other studies, and will evaluate the efficacy and safety of '786 for inducing a response and remission (reduction or disappearance of symptoms) and maintaining remission in more than 2,500 patients with moderately-to-severely active Crohn's disease. The initial pivotal induction study is a randomized, double-blind, placebo-controlled trial that will involve approximately 600 patients to evaluate 500 mg of '786 once or twice daily. The primary and key secondary endpoints are the proportion of subjects achieving a treatment-induced clinical response, based on the Crohn's Disease Activity Index, and the proportion of subjects achieving clinical remission. Source: PRNewswire 1/12/11

Company and Institute Join Efforts to Fight Cancer

AstraZeneca and Sarah Cannon Research Institute (SCRI) in January announced that SCRI will lead the clinical development of a novel targeted oncology compound from AstraZeneca. Under the agreement, SCRI will collaborate with AstraZeneca to provide clinical program development expertise, clinical program design, medical oversight, and trial management. The first clinical trial to be conducted under the agreement was initiated in November 2010, with the first patient enrollment into that clinical trial on November 23. The collaboration involves SCRI assisting AstraZeneca with both the design and delivery of a new agent from its first studies in cancer patients to proof of concept at the conclusion of Phase II. Source: PRNewswire 1/11/11

Randomized Phase II Trial Begins for Chronic Hepatitis C Therapy

Peregrine Pharmaceuticals, Inc. announced in January that it has initiated a randomized Phase II clinical trial in patients with previously untreated genotype-1 hepatitis C virus (HCV) infection. This open-label trial will determine the early virologic response (EVR) rate of patients taking Peregrine's bavituximab, a phosphatidylserine-targeting monoclonal antibody with immune-modulating potential, in combination with the antiviral drug ribavirin versus standard of care, pegylated interferon alpha 2a and ribavirin. Peregrine also expects to complete enrollment shortly in an ongoing Phase Ib HCV trial and report data by mid-year. The new Phase II trial is designed to build on three prior Phase I HCV trials, which the company says have demonstrated its antibody's acceptable safety and promising signs of antiviral activity. In the multicenter trial, up to 66 patients will be randomly assigned to one of three treatment arms. Patients will receive daily oral ribavirin (1,000 mg) with either weekly bavituximab (0.3 mg/kg or 3 mg/kg) or PEG-IFN alpha-2a (180 µg) for up to 12 weeks and will be tested for safety parameters and antiviral activity. The primary endpoint of the study is the proportion of patients achieving EVR, an early predictor of which patients are likely to clear virus with continued treatment. Secondary endpoints include safety, tolerability, and HCV viral kinetics. Source: Marketwire 1/10/11

Phase III Under Way for Treatment of Chronic Bacterial Infections in Cystic Fibrosis Patients

Mpex Pharmaceuticals, Inc. in January announced that it has initiated its Phase III clinical trial program with Aeroquin™ (MP-376) for the treatment of pulmonary infections in patients with cystic fibrosis (CF). Aeroquin is Mpex's proprietary aerosol formulation of levofloxacin, an antibiotic that has potent activity against key bacterial pathogens in CF, including Pseudomonas aeruginosa. The first study in this program is a multicenter, international, randomized, double-blind, placebo-controlled trial (Mpex 207) that is expected to enroll approximately 300 stable CF patients to evaluate the safety, tolerability, and efficacy of 240 mg of Aeroquin administered twice daily using an optimized, investigational nebulizer system for 28 days. The primary efficacy endpoint to be assessed in the trial will be time to exacerbation. Additional endpoints include time to need for antipseudomonal antimicrobials, as well as change from baseline to day 28 in lung function, the respiratory domain score of the CFQ-R, and sputum P. aeruginosa density. An additional Phase III trial comparing Aeroquin to TOBI® (tobramycin inhalation solution) over three 28-day cycles (Mpex 209) is expected to begin enrolling patients in the next several weeks. A previous Phase IIb study in 151 CF patients (Mpex 204) demonstrated that Aeroquin had a significant impact on bacterial load, respiratory function, and time to need for antipseudomonal antibiotics versus placebo in a heavily treated patient population. Results from the Phase III program are expected in mid-2012. Source: PRNewswire 1/10/11

Enrollment Completed for Phase III Chronic Kidney Disease Study

Dynavax Technologies Corp. in January announced completing the enrollment of its Phase III study of Heplisav™, the company's novel vaccine for the prevention of hepatitis B infection, in subjects with chronic kidney disease. The study, conducted in the U.S., Germany, and Canada, included 69 sites. To date, more than 500 first immunizations have been administered. According to the protocol, all patients will receive immunizations over a period of six months. The primary endpoint of the study is noninferiority of three injections of Heplisav at times 0, 1, and 6 months versus eight injections of Engerix-B® consisting of double doses at times 0, 1, 2, and 6 months. The company expects the last immunizations to be administered in June 2011. In September 2010, Dynavax reported that the first subjects enrolled in the study were 12 months past their first dose, and that no safety issues had been identified by the data safety monitoring board for the trial. In a completed pivotal Phase III trial, Heplisav demonstrated increased, rapid protection with fewer doses than current licensed vaccines. The product combines hepatitis B surface antigen with a proprietary Toll-like Receptor 9 agonist known as ISS to enhance the immune response. Source: Marketwire 1/10/11

Company Files IND for Phase I Study of Cancer Drug

Helix BioPharma Corp. in January announced that it has filed an Investigational New Drug (IND) application with the Food and Drug Administration (FDA) seeking approval to perform its planned Phase I clinical safety and tolerability study of its cancer drug candidate L-DOS47. L-DOS47 is an immunoconjugate drug designed to modify the microenvironmental conditions of cancer cells in a manner that leads to their destruction, and is intended to offer an innovative approach to the first-line treatment of inoperable, locally advanced, recurrent or metastatic non-small cell lung cancer. The IND review process typically requires 30 days, during which the FDA will decide if an applicant is permitted to proceed with its proposed clinical trial. The proposed Phase I study is planned to be an open-label, first-in-human study to primarily evaluate the safety and tolerability of L-DOS47. This study is therefore planned to be conducted in patients with refractory solid cancerous tumors of any type, with a view to maximizing the rate of patient recruitment. The study will begin with a dose of 0.13 micrograms of L-DOS47 per kilogram of patient body weight. L-DOS47 will be infused in ascending dose levels in groups of three-to-six patients per ascending dose level once weekly for three weeks followed by one week of rest (one treatment cycle = four weeks), over four planned treatment cycles. The total number of patients to be enrolled in the study will ultimately depend on how many ascending dose levels are required to reach the maximum tolerated dose; however, based on the company's preclinical studies to date, it currently estimates that the study will enroll approximately 30 to 50 patients. Source: Marketwire 1/7/11

Positive Results Seen in Phase II of Treatment for Liver Transplant Patients

LifeCycle Pharma A/S has announced positive top-line results from a Phase II clinical trial involving 58 patients comparing LCP-Tacro™ tablets administered once-daily versus Prograf® (tacrolimus) capsules (Astellas Pharma) administered twice-daily in de novo liver transplant patients for one year. These data confirm the previous positive experience with LCP-Tacro in stable kidney and liver transplant patients and support comparability of the company's extended release tablet formulation of tacrolimus when compared to twice-daily Prograf capsules. Further, the results indicate that LCP-Tacro tablets may be safely and efficaciously administered once-daily immediately following a liver transplant. Results from the 14-day pharmacokinetic portion of this study were reported in August 2009. After the initial 14-day period, patients were maintained on either LCP-Tacro or Prograf for one year to assess longer-term safety and efficacy in a comparative setting. While not sized and powered to demonstrate safety and efficacy at a statistically relevant level, once-daily LCP-Tacro appears to be as well-tolerated as the currently approved, immediate release, twice-daily product Prograf. The company is looking forward to completing two Phase III trials in kidney transplant patients and announcing the data from those studies in 2011 and 2012. The Phase III program consists of an ongoing, fully enrolled study in 326 patients with stable kidney transplants along with an ongoing Phase III study in de novo kidney transplant patients under a Special Protocol Assessment that was agreed to with the U.S. Food and Drug Administration in August 2010. The Phase II clinical trial was an open-label, multicenter, prospective, parallel-group study. Source: PRNewswire 1/6/11

Enrollment Completed in Phase II Onychomycosis Study

NB Therapeutics, Inc. in early January announced completion of patient enrollment in its Phase II clinical trial evaluating NBT-320, which is the use of iontophoresis and a novel formulation of terbinafine for the treatment of onychomycosis, commonly known as toenail fungus. Separately, the company announced that it had changed its name from Nitric BioTherapeutics to NB Therapeutics. The study enrolled 165 patients at nine sites in the U.S. and Canada, and is evaluating the safety and efficacy of using iontophoresis to deliver a proprietary, ionized formulation of terbinafine to treat moderate onychomycosis. Preliminary clinical results for NBT-320 will be available in the first quarter of 2011, with final results available in the fourth quarter. Source: Marketwire 1/5/11

Special Protocol Assessment Agreed on for Pivotal Trial in Progressive Supranuclear Palsy

Allon Therapeutics Inc. announced in January that it has reached agreement with the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for a pivotal Phase II/III clinical trial to evaluate the company's lead neuroprotective drug candidate, davunetide, as a potential treatment for progressive supranuclear palsy (PSP), a rapidly progressing and fatal degenerative brain disease. The SPA is a mechanism through which the FDA and Allon reach agreement on the design, size, clinical endpoints, and data analysis of a clinical trial that is intended to support an efficacy claim in a New Drug Application for regulatory approval. The SPA ensures that the agreed clinical trial design meets the FDA's expectations for a pivotal study. Allon believes that if this pivotal study generates statistically significant and consistent data, davunetide will be considered by FDA for approval in PSP. The randomized, double-blinded, placebo-controlled trial in PSP will enroll 300 patients in the United States, Canada, United Kingdom, France, Germany, and Australia. Study participants will receive either placebo or 30 mg of davunetide administered twice daily for a period of 12 months. The primary outcome measures will be the Progressive Supranuclear Palsy Rating Scale and the Schwab and England Activities of Daily Living scale. Secondary measures will include Clinical Global Impression and brain imaging by magnetic resonance tomography. Additional exploratory endpoints include cognitive and executive function as well as cerebrospinal fluid biomarkers. Allon previously announced that davunetide received orphan drug designation in the United States (January 12, 2010) and the European Union (March 17, 2010), Fast Track Status with the FDA (April 6, 2010), and that davunetide met the primary outcome measure of safety and tolerability, with potential trends from secondary efficacy endpoints, in a pilot study of 12 patients suffering PSP and related tau pathology disorders (October 8, 2010). Source: Marketwire 1/4/11

Positive Results Seen for Patients Undergoing Ureteroscopy

Omeros Corp. in late December announced results from the Phase I/II clinical trial of OMS201, the company's urological PharmacoSurgery™ product candidate. OMS201 is a proprietary combination of an anti-inflammatory agent and a smooth muscle relaxant, each with well-known safety and pharmacologic profiles. Based on the successfully completed Phase I trial of a lower concentration of OMS201, this Phase I/II study was designed to evaluate the safety and systemic absorption of two sequentially higher concentrations of OMS201 added to standard irrigation solution and delivered to patients undergoing ureteroscopy for removal of ureteral or renal stones. This multicenter, double-blind, placebo-controlled study also explored potential efficacy endpoints, but was not powered to assess efficacy. Based on an interim analysis of the pharmacokinetic data, which demonstrated low maximal systemic absorption of the active ingredients, trial enrollment was truncated from the originally planned 36 patients to a total of 24 patients. OMS201 was safe and well tolerated in this study. "We are pleased with the results of this trial, which demonstrated an absence of side-effects even at a concentration of OMS201 10 times higher than that examined in our earlier Phase I clinical study," said Gregory A. Demopulos, MD, chairman and chief executive officer of Omeros. "These data will help us to design subsequent trials evaluating the efficacy and safety of OMS201 in patients undergoing urologic procedures." Source: PRNewswire 12/29/10

Company Initiates Phase II Evaluation of Combination Treatment for Liver Cancer

Vicus Therapeutics, LLC, in December announced the initiation of a Phase II trial evaluating VT-122, a novel investigational combination of etodolac and propranolol, and Nexavar® (sorafenib) tablets, as a potential new treatment option for patients with advanced liver cancer (hepatocellular carcinoma), systemic inflammation, and cachexia. The randomized, open-label, multicenter study will evaluate whether VT-122 in combination with Nexavar increases a composite measurement of pain, performance status, and lean body mass, as compared to Nexavar alone. The secondary efficacy endpoints of this study are cancer and cachexia specific symptoms, duration of Nexavar therapy, and overall survival. The study is expected to enroll 80 patients in the United States, with enrollment completed by the end of 2011. Vicus, Bayer HealthCare Pharmaceuticals, Inc., and Onyx Pharmaceuticals, Inc. have entered into an agreement pursuant to which Bayer and Onyx have agreed to support the study. The terms of the agreement are confidential. Source: PRNewswire 12/27/10

Phase III Enrollment Completed for Cystic Fibrosis Study

PTC Therapeutics, Inc. announced in December that it has completed enrollment of a Phase III clinical trial of ataluren, an investigational new drug, in patients with nonsense mutation cystic fibrosis (nmCF). The 48-week study is designed to determine whether ataluren can improve lung function in patients with nmCF, and has enrolled 238 patients at 36 sites in North America, Europe, and Israel. Patients who complete the treatment phase of this trial are eligible to participate in a 48-week, open-label extension study, which has begun enrolling patients. Ataluren is a protein restoration therapy designed to enable the formation of full-length, functional CF transmembrane regulator (CFTR) protein in patients with CF due to a nonsense mutation. CFTR is a critical protein lacking in CF patients. The primary objective of the registration-directed, double-blind, placebo-controlled study is to determine whether ataluren can improve lung function in patients with nmCF, as measured by forced expiratory volume in one second (FEV1). Additional secondary endpoints are evaluating other aspects of patient function, drug activity, and safety. Patients were randomly assigned to one of two treatment arms: ataluren (10 mg/kg morning, 10 mg/kg midday, 20 mg/kg evening) or placebo (morning, midday, evening). The U.S. Food and Drug Administration (FDA) and the European Commission have granted ataluren Orphan Drug status for the treatment of nmCF and nonsense mutation Duchenne and Becker muscular dystrophy. The FDA has also granted ataluren Subpart E designation for expedited development, evaluation, and marketing for CF and dystrophinopathy and Fast Track designation for the development of treatment for nonsense mutation dystrophinopathy. 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 12/21/10

Trial Begins for Kinase Inhibitor in Combination with Monoclonal Antibody

Oncothyreon Inc. in December announced enrollment of the first patient in a Phase I/II trial of PX-866 in combination with the chimeric monoclonal antibody cetuximab (Erbitux®). PX-866 is a small molecule compound designed to inhibit the activity of phosphatidylinositol-3-kinase (PI-3K), a component of an important cell survival signaling pathway. The primary objective of the Phase I dose-escalation portion of the trial is to determine the maximum tolerated or recommended daily dose of PX-866 to be given in combination with the standard dose of cetuximab administered weekly to patients with either progressive metastatic colorectal carcinoma (CRC) or progressive, recurrent, or metastatic squamous cell carcinoma of the head and neck (SCCHN). The Phase II portion is designed as a screening trial and will be an open-label, randomized evaluation of the antitumor activity and safety of PX-866 administered at the maximum tolerated or recommended dose in combination with cetuximab, versus cetuximab alone, in two groups of patients not previously treated with cetuximab. Group 1 will enroll patients with metastatic CRC who have a history of progression or recurrence following prior treatment with irinotecan and oxaliplatin containing regimens or who are intolerant of irinotecan. Patients with CRC and Kras mutations are excluded from the trial. Group 2 will enroll patients with progressive, recurrent, or metastatic SCCHN. The two groups will be randomized and evaluated independently. The primary endpoint of the Phase I portion of the trial is safety, and it will enroll up to a total of 18 patients at three different dose levels of PX-866 in combination with cetuximab. Up to 144 patients may be enrolled in the Phase II portion of the study, including 72 (36 per arm) in each group. The primary endpoint of the Phase II portion is objective response rate based on RECIST criteria. Secondary endpoints include progression-free and overall survival, duration of response, and disease control rate. Source: PRNewswire 12/20/10

Novel Drug Offers Hope for CF Patients

Cystic fibrosis (CF) patients with normal to mildly impaired lung function may benefit from a new investigational drug designed to help prevent formation of the sticky mucus that is a hallmark of the disease, according to researchers involved in a Phase III clinical trial of the drug. Called denufosol, the investigational medication can be given early in the CF disease process, and may help delay the progression of lung disease in these patients, the researchers found. The findings were published online ahead of the print edition of the American Journal of Respiratory and Critical Care Medicine. Researchers enrolled 352 CF patients 5 years of age or older to receive either inhaled denufosol or placebo three times daily for 24 weeks, followed by a 24-week open-label period when all patients received denufosol. At baseline, most patients enrolled had mild impairment of lung function and were taking multiple medications to control their symptoms. Patients' exhalation rates and lung volume were measured throughout the study, and also were monitored for adverse events, such as cough, congestion, fever, or sinusitis. At the end of the 24-week period, researchers determined patients who received denufosol had better lung exhalation rates than those in the placebo group, whose exhalation volumes remained relatively unchanged from the start of the study. Both groups had similar numbers and types of adverse events, with the denufosol patients experiencing significantly fewer headaches and lower rates of sinusitis and runny nose. A second, similar Phase III trial incorporating a longer placebo-controlled treatment phase is ongoing to further investigate the effectiveness of denufosol in patients with CF. Source: EurekAlert! 12/17/10

Trial of Autism Early Intervention Reveals Significant Improvements

In a study recently published in the Journal of Child Psychology and Psychiatry, researchers from the Kennedy Krieger Institute found that early intervention can improve the core symptoms of autism spectrum disorders (ASD) in very young children. This is the first randomized clinical trial measuring how a group-based early intervention model impacts social development in toddlers with ASD. The most significant improvements were found in how the children connected and socialized with others, a defining stumbling block for children with autism. Participants included two groups of 24 toddlers with ASD, ages 21 to 33 months, who received identical intervention for six months. However, one group received a greater number of orchestrated opportunities for social engagement. Researchers found that intervention led to improvements in both groups. However, the most significant finding was that the children who received more of the socially directed intervention developed greater socially engaged imitation, which increased from 17 percent of imitated acts being paired with eye contact to 42 percent. This skill was generalized, or carried over into “real life” outside the classroom, and maintained through the six-month follow-up. Similar improvements were observed in the group for initiation of joint attention (pointing out things of interest, showing and giving for social purposes) and shared positive affect (smiling paired with eye contact). Specifically, how frequently toddlers initiated joint attention more than tripled from pre- to post-treatment, and the shared positive affect more than doubled. Overall, the children receiving the socially directed intervention made 10 months of nonverbal cognitive gains in only six months time when compared to the other group. The second most significant finding was that toddlers in both groups made improvements in expressive language (spoken language), with the greatest gains occurring during the time that the intervention was occurring. This indicates that the improvement was due to the intervention. Source: Newswise 12/15/10

Phase II Study Focuses on Nasal Spray for Seasonal Allergic Rhinitis

ISTA Pharmaceuticals, Inc. in December announced it has initiated a Phase II clinical study of bepotastine besilate nasal spray for the treatment of symptoms associated with seasonal allergic rhinitis, the inflammation of the nasal passages caused by allergies. The randomized, placebo-controlled, parallel-group environmental study will evaluate the safety and efficacy of bepotastine besilate, dosed twice daily, in patients presenting with allergic rhinitis caused by one of the most potent seasonal allergy triggers, Mountain Cedar pollen. ISTA expects to enroll approximately 600 patients in Texas who will be treated with either bepotastine besilate nasal spray or placebo for two weeks. Patients will grade both individual nasal and ocular symptoms on a daily basis. ISTA submitted the Investigational New Drug application to the U.S. Food and Drug Administration for bepotastine besilate nasal spray in November. Bepotastine besilate is a nonsedating, highly selective antagonist of the histamine H1 receptor; it has been approved in Japan for systemic use in the treatment of allergic rhinitis since 2000 and for urticaria/pruritus since 2002. Source: PRNewswire 12/14/10

Phase III Trial in Metastatic Melanoma Suspended

Eli Lilly and Co. announced in December that it has suspended its global Phase III study evaluating tasisulam, an investigational, small-molecule anticancer compound, as a second-line treatment for those with unresectable or metastatic melanoma. Lilly, in consultation with an independent data monitoring committee, recommended a "full clinical hold," because of safety concerns. A full clinical hold ensures that no new or existing patients in the trial receive additional doses of the compound, allowing researchers the time to fully analyze existing data. Lilly notified regulatory agencies and contacted all trial investigators to provide details on how to manage individuals enrolled in the trial. "We are thoroughly reviewing the clinical trial data to understand what modifications to the study protocol or dosing would be needed to improve patient safety on this trial," said Richard Gaynor, MD, vice president of oncology product development and medical affairs for Lilly. Lilly continues to develop tasisulam as part of an extensive clinical development program across a wide range of tumors, including soft tissue sarcoma, breast, ovarian, and renal cancers, as well as non-small cell lung cancer and acute leukemia. At this time, these trials continue without modification because the dosing of tasisulam is different. Lilly is closely evaluating patient safety within these trials on an ongoing basis. The Phase III trial sought to compare the efficacy, safety, and tolerability of tasisulam versus paclitaxel, as a second-line treatment for those with metastatic melanoma. The study enrolled more than 300 patients in 18 countries. The primary endpoint of this study is overall survival. Tasisulam was granted orphan drug status for stage 2b-IV melanoma by the U.S. Food and Drug Administration in late 2009. Source: PRNewswire 12/13/10

Phase IIa Data Show Drug's Effect Against ALS

Cytokinetics, Inc. has announced the successful completion of its Phase IIa "Evidence of Effect" clinical trial of CK-2017357 in patients with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, during an oral presentation included in the Clinical Trials Session at the 21st International Symposium on ALS/MND in Orlando, Fla. A presentation on the double-blind, randomized, placebo-controlled, single-dose, crossover study was made by Jeremy M. Shefner, MD, PhD, professor and chair of the Department of Neurology at the Upstate Medical University at the State University of New York. CK-2017357 is the lead drug candidate from the company's skeletal muscle contractility program. In this trial, a single 250 mg dose of CK-2017357, a single 500 mg dose of CK-2017357, and a single matching dose of placebo were each administered once, in a double-blind fashion and in random order, at least six days apart to male and female ALS patients. The maximum CK-2017357 plasma concentration generally was achieved between three and six hours after dosing, which is when most assessments were made; some were also repeated at 24 hours after dosing. The investigators concluded that both patients and investigators perceived a positive change in the patients' overall status at six hours after dosing with CK-2017357. Patients were more than twice as likely to assess themselves as "better" when their plasma concentrations were above 9 mcg/mL than on placebo, while the investigators were more than three times more likely to assess their patients as "better" when the patients' plasma concentrations were in that range. The investigators proposed that these improvements in the patients' and investigators' global assessments may have resulted from a decrease in the fatigability of their muscles, as evidenced by data from a test of submaximal hand-grip fatigability. The company is now planning to proceed into a multiple-dose clinical trial to understand how longer-term dosing of CK-2017357 may impact the functional status of these patients. CK-2017357 has been granted orphan drug designation by the U.S. Food and Drug Administration for the potential treatment of ALS. Source: Marketwire 12/13/10

Drug Demonstrates Significant Efficacy for Metastatic Breast Cancer

Nektar Therapeutics in December announced positive results from a Phase II clinical study evaluating single-agent NKTR-102 in patients with metastatic breast cancer during the 33rd Annual CTRC-AACR San Antonio Breast Cancer Symposium. NKTR-102, a novel investigational topoisomerase I inhibitor-polymer conjugate, is Nektar's lead oncology candidate and is being evaluated in multiple cancer indications. The randomized Simon two-stage study evaluated two 145 mg/m2 dose schedules of single-agent NKTR-102, every two weeks (q14d) and every three weeks (q21d), in 70 metastatic breast cancer patients who failed a prior taxane therapy. Eighty-seven percent (61/70) of patients in the study received a prior anthracycline/taxane with or without capecitabine. A total of 66 of the 70 patients treated in the study were assessable for the primary endpoint of objective tumor response rate (ORR), including confirmed complete and partial responses per RECIST. As of October 26, 2010, confirmed ORR for all evaluable patients was 32 percent (10/31) for the q14d schedule and 26 percent (9/35) for the q21d schedule, including two confirmed complete responses (CRs) on the q14d schedule. An additional four patients had near CRs, with 100 percent disappearance of all target lesions. The combined ORR for all evaluable patients was 29 percent (19/66). Clinical benefit rate for the evaluable patients was 41 percent. Source: PRNewswire 12/12/10

Pulmonary Arterial Hypertension Trial Halted in the Interest of Patient Safety

Pfizer Inc. announced in December that, in the interest of patient safety, it is voluntarily withdrawing Thelin® (sitaxentan) for the treatment of pulmonary arterial hypertension (PAH) in regions where it is approved (the European Union, Canada, and Australia). In addition, Pfizer is discontinuing clinical studies of Thelin worldwide. Pfizer's decision was based on a review of emerging safety information from clinical trials and postmarketing reports. While liver toxicity is a known complication of the class of drugs to which Thelin belongs, a new potentially life-threatening idiosyncratic risk of liver injury with Thelin has been observed. Given the availability of alternate treatments, Pfizer has concluded that the overall benefit of Thelin no longer outweighs the risk in the general population of PAH patients. The company has notified health authorities about this finding and its decision to voluntarily withdraw Thelin from the market and stop clinical studies. Pfizer recommends that no new patients be prescribed Thelin and that patients receiving Thelin be transitioned to appropriate alternate therapies as soon as safely possible according to best local practice. Patients taking Thelin or participating in Thelin studies are advised to consult with their healthcare professional as soon as possible. Patients should not stop taking Thelin until they speak to their healthcare professional. Source: PRNewswire 12/10/10

Phase II Plan Completed for Treatment of Memory Loss in CABG Patients

Neurokine Pharmaceuticals Inc. has announced the completion of its new clinical trials plan to test the effects of NK-001 in the treatment of Alzheimer's type memory loss in patients undergoing coronary artery bypass graft (CABG) surgery. The plan will be to carry out trials in 50 patients following CABG surgery and to test these patients for up to 12 months following surgery for cognitive impairment (similar to Alzheimer's). The patients will be divided in two groups; 25 will receive NK-001 and 25 will receive placebo. The trials will be carried out in four to six sites with cardiosurgery and psychiatry expertise in Europe, with completion expected within 12 to 18 months. Source: Marketwire 12/9/10

Company Receives FDA Clearance to Reinitiate Testing of Anthrax Antitoxin

PharmAthene, Inc. announced in December that the U.S. Food and Drug Administration (FDA) has provided formal consent for the company to reinitiate clinical testing of its anthrax antitoxin, Valortim®, after lifting the partial clinical hold placed on the program in late 2009. The company has proposed moving forward with a Phase I intravenous dose-escalation study, which is expected to commence in the next several weeks. Valortim is a fully human antitoxin monoclonal antibody being developed for the prevention and treatment of inhalational anthrax. Animal studies suggest that Valortim has the potential to provide protection against anthrax infection when administered prophylactically (prior to the emergence of symptoms of anthrax infection) and also may increase survival when administered therapeutically (once symptoms become evident). The Valortim project has been supported by the National Institute of Allergy and Infectious Disease in the National Institutes of Health and the Biomedical Advanced Research and Development Authority in the Department of Health and Human Services. Source: PRNewswire 12/9/10

Phase II Major Depression Study Focuses on Triple Reuptake Inhibitor

Euthymics Bioscience, Inc. in December presented Phase II clinical data demonstrating that its lead product candidate EB-1010, a next-generation antidepressant, is effective for treating major depressive disorder (MDD) based on multiple standard measures of outcome for depression. EB-1010 also improved measures of anhedonia, a hallmark symptom of MDD, which is characterized by the inability to experience pleasure. The data further demonstrate that EB-1010 is well tolerated, without the weight gain or sexual dysfunction associated with the most common pharmacological treatments for depression. The data were presented at the 49th annual meeting of the American College of Neuropsychopharmacology in Miami, Fla. Euthymics' EB-1010 is a novel unbalanced triple reuptake inhibitor antidepressant intended for patients with MDD who do not respond adequately to selective serotonin reuptake inhibitors. The data presented are from a multicenter, randomized, placebo-controlled, double-blind, six-week study in patients with MDD. Sixty-three patients in the U.S. and in Eastern Europe were randomized, and 56 patients were included in the modified intent-to-treat population at a titrated dose of 50 mg/day for two weeks and then 100 mg/day for the remaining four weeks. Efficacy results were "statistically significantly" superior when compared to placebo on the primary outcome measure, the Montgomery-Åsberg Depression Rating Scale (MADRS, 18.16 vs. 21.99). Secondary measures including the Clinical Global Impression-Improvement scale, compared to placebo as well as anhedonia factor scores derived from the MADRS, were also improved. The company plans to initiate TRIADE, a large multicenter Phase II/III clinical trial of EB-1010 in major depression, in the first half of 2011. Source: EurekAlert! 12/8/10

Long-Term Phase III Erectile Dysfunction Study Confirms Drug's Efficacy

VIVUS, Inc. in December announced positive results from TA-314, a Phase III, pivotal, open-label, safety study of avanafil, an investigational drug for the treatment of erectile dysfunction (ED). The study met all primary endpoints by demonstrating improvement from baseline in erectile function as measured by the Sexual Encounter Profile and improvements in the International Index of Erectile Function. In the study, patients treated with avanafil who attempted sexual intercourse within the first 15 minutes of dosing had success rates of 80 percent. TA-314 confirms the longer term safety and efficacy results observed in the previously reported placebo-controlled Phase III studies of avanafil in patients with ED. The open-label design allowed the more than 700 enrolled patients to use avanafil as needed and at a dose of their choosing. With the completion of this study, the company anticipates the completion of the New Drug Application filing for avanafil in the second quarter of 2011. The avanafil Phase III program consists of four pivotal studies: TA-301 (REVIVE), TA-302 (REVIVE-Diabetes), TA-303, and TA-314. Source: PRNewswire 12/6/10

Positive Results Seen for Treatment for Acute Attacks of Hereditary Angioedema

Shire plc in early December announced topline results from FAST-3 (For Angioedema Subcutaneous Treatment), the largest of the Phase III trials studying the use of Firazyr® (icatibant) for treatment of acute attacks of hereditary angioedema (HAE). The study showed that patients receiving treatment with Firazyr experienced a significantly faster time to onset of symptom relief from individual and combined cutaneous and abdominal HAE symptoms, compared to those receiving placebo. Firazyr provided a highly statistically significant and clinically meaningful benefit relative to placebo for the primary endpoint of time to onset of symptom relief for the first attack after study enrollment. This was measured by a 50 percent reduction in a composite symptom score assessed by the patient. The median time to onset of symptom relief for Firazyr by this measure was 2.0 hours, compared to 19.8 hours for placebo. Firazyr also provided a significantly shorter time to onset of symptom relief of the patient's primary (main) symptom. This secondary efficacy endpoint was measured by a 30 percent reduction in symptom score. The median time to onset of relief for Firazyr by this measure was 1.5 hours, compared to 18.5 hours for placebo. Firazyr is currently approved in 37 countries worldwide, including the countries of the European Union, for the symptomatic treatment of acute attacks of HAE in adults (with a C1-INH deficiency). In 2008, the U.S. Food and Drug Administration (FDA) issued a not approvable letter for Firazyr. It was agreed by Shire and the agency that an additional clinical study (FAST-3) would be required to support the New Drug Application filing in the US. Shire now expects to file a complete response to the FDA's not approvable letter early in 2011. The FAST-3 study, conducted in 67 sites in nine countries, was a randomized, double-blind, placebo-controlled, multicenter trial of Firazyr administered by subcutaneous injection for the treatment of patients with acute attacks of HAE. A total of 88 patients who presented with moderate to very severe cutaneous and/or abdominal symptoms were enrolled in the double-blind phase, with an approximately equal number in each arm of the study. Patients with HAE attacks who presented with mild to moderate laryngeal symptoms were also randomized and enrolled in the double-blind phase. Patients who presented with severe laryngeal attacks immediately received open-label Firazyr. All laryngeal patients were considered additional to the 88 patients with abdominal and/or cutaneous attacks who were randomized and enrolled. The primary analysis population consisted of those patients with cutaneous and/or abdominal symptoms who were randomized to either Firazyr or placebo (the nonlaryngeal intent-to-treat population). After the first attack, patients had the option for subsequent attacks to be treated with open-label Firazyr. Source: PRNewswire 12/1/10

HIV Trial Looks at Potential Benefits of Treating Recently Infected Patients

For most people in high-income countries, HIV is considered a chronic illness that can be managed with medication, but the virus still causes extensive damage to the immune system, and treatment with antiretrovirals is a lifelong commitment. Once started, usually within three to five years following infection, the course of treatment needs to be strictly followed and taken for life. A Wellcome Trust-funded clinical trial is examining whether it is possible to limit damage to the immune system by treating people soon after they are infected with HIV with a short course of antiretroviral drugs, and therefore delay the time to commencing long-term antiretroviral treatment. The clinical trial study, known as SPARTAC (Short Pulse Anti Retroviral Therapy at HIV Seroconversion), is following 371 individuals, recruited in eight countries across four continents. The trial, which began recruiting at the end of 2004, is due to be completed in late 2010, with the results announced in 2011. If positive, the findings could have a major impact on how HIV is managed worldwide. Researchers at Imperial College London, together with colleagues from the Medical Research Council Clinical Trials Unit and the University of Oxford, have been conducting the SPARTAC trial in collaboration with investigators across the U.K. and Ireland, Uganda, South Africa, Australia, Brazil, Italy, and Spain. The trial has been undertaken in both high-income and resource-poor settings and across all the key different risk groups: heterosexuals, men who have sex with other men, and African women. Source: EurekAlert! 11/30/10

Enrollment Begins for Pivotal Trial of HRS Drug

Ikaria, Inc. announced that it has enrolled the first patients in its pivotal Phase III trial for Lucassin® (terlipressin), which is being developed for the treatment of hepatorenal syndrome (HRS) type 1, an orphan-designated condition for which there currently are no approved drugs in the United States. The multicenter, randomized, placebo-controlled, double-blind trial is known as REVERSE. HRS type 1 is the development of kidney failure in patients with late-stage liver cirrhosis in the absence of any other cause. It is characterized by rapid onset of renal failure with a high mortality rate that exceeds 80 percent within three months. REVERSE will compare terlipressin in combination with albumin to placebo with albumin, and will have a primary endpoint of HRS reversal, which is defined as two serum creatinine values of less than or equal to 1.5 mg/dL taken at least 48 hours apart, without any intervening hemodialysis, transplant, or elevation of creatinine above a prespecified level. Transplant-free survival and overall survival are among the secondary endpoints of the trial. Lucassin is a synthetic vasopressin analogue that acts via the vasopressin V1a receptor as a systemic vasoconstrictor, mainly in the splanchnic (abdominal) circulation, which appears to increase effective arterial volume and improves renal blood flow, thereby improving renal function in patients with HRS. Terlipressin is approved in France, Ireland, Spain, and South Korea for the treatment of patients with HRS type 1. Terlipressin is not approved by the Food and Drug Administration for use in the United States. Source: PRNewswire 11/30/10

Phase II Vaccine Trial Under Way for Primary Prevention of Clostridium Difficile

Sanofi Pasteur announced in late November that it has started its Phase II clinical study of a vaccine for primary prevention of Clostridium difficile infection (CDI). The trial starting in the United States is focused on evaluating prevention of the first episode of CDI in at-risk individuals, including adults with imminent hospitalization or current or impending residence in a long-term care or rehabilitation facility. Trial leaders hope to recruit approximately 650 participants at some 30 healthcare centers across the U.S. Hospital-acquired infections caused by C. difficile are a considerable problem in many industrialized countries, including the U.S., Canada, and Europe. It is estimated that there are about 500,000 cases of CDI in the U.S. alone, with annual costs to the healthcare system of $3.2 billion. Source: PRNewswire 11/29/10

First Patient Enrolled in First-in-Human Study of Stent

Micell Technologies,™ Inc. in late November announced it has enrolled at Mercy Hospital in Auckland, New Zealand, the first patient in DESSOLVE I (DES with Sirolimus and a bioabsorbable pOLymer for the treatment of patients with de noVo lEsions in the native coronary arteries), a first-in-human clinical trial of the company's investigational MiStent™ drug-eluting coronary stent system (MiStent DES). DESSOLVE I is a prospective, open-label, nonrandomized, single-arm study that is expected to enroll 30 patients at five clinical sites in Belgium, Australia, and New Zealand. Candidates for the trial are patients with documented stable or unstable angina pectoris or ischemia. The primary endpoint is in-stent late lumen loss, as measured with angiography in treated de novo lesions ranging in diameter from 2.5 to 3.5 mm and amenable to treatment with a maximum 23 mm long stent. Along with secondary clinical endpoints, such as major adverse cardiac events and revascularization rates, intravascular ultrasound and optical coherence tomography will be employed at multiple timepoints. The DESSOLVE I study uses multiple imaging modalities to better understand the time to complete tissue coverage of the stent struts relative to polymer absorption. The MiStent DES is designed to maintain the polymer-drug matrix on the stent only as long as drug delivery is required. It slowly reverts to a bare-metal stent by the time drug treatment is completed. In preclinical trials, the drug completely eluted and the polymer was eliminated within 90 days in vivo, resulting in a bare metal stent. The stent system is an investigational device, and not yet approved or available for sale in any market. Source: PRNewswire 11/29/10

Department of Defense Funds Skin Substitute's Move into First Trials for Adults

The U.S. Department of Defense recently awarded more than $18 million in funding to a unit of Lonza Group, Ltd. for the development and commercialization of the therapeutic candidate, PermaDerm for the treatment of severe burns among U.S. troops and civilians. Regenicin, Inc. has an agreement with Lonza pursuant to which Regenicin has been charged to obtain Food and Drug Administration (FDA) approval for the commercial sale of PermaDerm. The funding will assist Regenicin and Lonza in advancing the clinical trials to be conducted in connection with the FDA approval process. PermaDerm, an engineered skin substitute grown from a patient's own skin cells, has already been used to treat more than 150 pediatric, catastrophic burn victims through an Investigation Device Exemption issued by FDA. This is PermaDerm's first clinical trial to be conducted on adults, a major milestone for achieving premarket approval by the FDA. The initial trial will contain 10 patients, both male and female, between the ages of 18 and 40, who suffer third-degree burns. These trials and future trials will take place at the United States Army Institute of Surgical Research at Fort Sam Houston and at a second site to be determined. Source: PRNewswire 11/22/10

Positive Phase IIb Results Announced for Chronic Kidney Disease Treatment

Reata Pharmaceuticals and Abbott in November announced data from a Phase IIb study that suggest that bardoxolone methyl, an investigational treatment for chronic kidney disease (CKD), may reduce the stage of CKD and improve estimated glomerular filtration rate (eGFR) and other measures of kidney function in the majority of patients receiving the drug. The data were presented at the American Society of Nephrology Renal Week Conference in Denver, Colo. The study evaluated patients with moderate (stage 3b) to severe (stage 4) CKD and type 2 diabetes. Approximately 60 percent of the patients receiving bardoxolone methyl experienced a reduction in the classification of the severity of their disease after 24 weeks of treatment. Only 17 percent of patients in the placebo group experienced such a reduction. Additionally, only 4 percent of patients in each bardoxolone methyl group experienced a worsening of CKD stage compared to 13 percent in the placebo group. The multicenter, randomized, double-blind clinical trial enrolled 227 CKD patients with type 2 diabetes who were randomized to receive once-daily doses of placebo or 25, 75, or 150 mg doses of bardoxolone methyl. The primary endpoint of the study was change in estimated GFR following 24 weeks of treatment. At week 24, patients treated with bardoxolone methyl experienced a mean increase in estimated GFR of over 10 mL/min/1.72m2, compared to no change in the placebo group. Approximately three-quarters of bardoxolone methyl-treated patients experienced an improvement in eGFR of 10 percent or more, including one-quarter who saw an improvement of 50 percent or more compared to less than 2 percent of patients on placebo. The company plans to initiate a Phase III study in the first half of 2011. Source: PRNewswire 11/20/10

Phase III Device Data Presented from Recurrent Glioblastoma Study

Data presented in November from a pivotal, Phase III, randomized clinical trial for patients with recurrent glioblastoma tumors suggest that Tumor Treating Fields (TTF) therapy may increase median survival time and improve quality of life scores compared to best standard of care chemotherapy. Professor Zvi Ram, chairman of the Department of Neurosurgery at Tel-Aviv Sourasky Medical Center, presented the data at the Society for Neuro-Oncology Annual Scientific Meeting. Physicians delivered the investigational TTF therapy to patients in the study using the NovoTTF-100A--a portable, noninvasive medical device. Investigators conducted this study under an approved Investigational Device Exemption at 28 centers in the U.S., Europe, and Israel, enrolling 237 patients with glioblastoma tumors that had recurred or progressed after initial treatment. Patients randomly received TTF therapy alone or an effective chemotherapy selected by physicians. The results reported expand on data announced earlier, which suggested that TTF therapy may be as effective as the best available chemotherapy in extending overall survival of patients with recurrent glioblastoma. In younger patients and patients with better functional status, the incidence of radiological tumor response to TTF therapy was double that seen in patients treated with chemotherapy. Patients under the age of 60 who were able to maintain normal daily activities at the time of enrollment achieved a significant increase in median overall survival time (8.8 vs. 6.6 months, n=110) and in the one-year survival rate (35 percent vs. 20 percent) when treated with TTF therapy versus effective chemotherapies. TTF therapy also produced a significant increase in survival time for patients who had failed treatment with bevacizumab (Avastin; Roche) prior to enrollment (4.4 vs. 3.1 months, n=44). Patients enrolled in the study also reported superior quality of life scores across a range of lifestyle and symptom categories for TTF therapy compared to the chemotherapy-treated control group. TTF therapy has been shown in vitro to slow and reverse tumor cell proliferation by inhibiting mitosis, the process by which cells divide and replicate. The NovoTTF-100A device, which weighs about six pounds (three kilograms), creates a low-intensity, alternating electric field within the tumor that exerts physical forces on electrically charged cellular components, preventing the normal mitotic process and causing cancer cell death prior to division. Novocure is now sponsoring a second Phase III study of TTF therapy at 26 centers in the U.S., Europe, and Israel. This study will enroll 283 patients with newly diagnosed glioblastoma tumors. Patients will be randomized (2 to 1) to receive TTF therapy and temozolomide (Temodar; Merck & Co.) or temozolomide alone (the current best standard of care). Novocure also recently reported results from a successful Phase II trial that studied TTF therapy in combination with chemotherapy for advanced non-small cell lung cancer at the European Society of Medical Oncology Congress. The NovoTTF-100A is an investigational device in the United States and has not been approved by the U.S. Food and Drug Administration for sale in the U.S. for any use. Novocure currently has CE Mark for the NovoTTF-100A and the treatment is available to patients in Europe. Source: PRNewswire 11/19/10

Dust Mite Vaccine Does Well in Phase II Study

Circassia Ltd in November announced successful clinical results from a Phase II study of its T-cell vaccine targeting house dust mite allergy. The study met each of the safety and efficacy endpoints, with the optimal treatment regimen achieving a major reduction in patients' reactions to house dust mite allergens. These results build on four earlier successful Phase II studies of Circassia's ToleroMune® technology, which scientifically validated the use of novel T-cell vaccines in treating allergies. Circassia is currently conducting a number of ongoing Phase II clinical trials with its therapies for grass (hayfever), cat, and ragweed allergies. Circassia undertook its most recent study in Quebec City, Canada, in 50 patients with confirmed house dust mite allergies. Patients received four standardized doses of ToleroMune T-cell vaccine over a number of weeks. During the study, investigators administered a challenge dose of house dust mite allergen to the volunteers' skin and eyes to assess the impact of the ToleroMune therapy. The results show that the optimal treatment regimen reduced each of the allergic reactions assessed during the study, achieving a therapeutic effect 32 to 87 percent greater than placebo. Circassia's technology utilizes allergen epitopes to generate regulatory T cells that suppress allergic immune responses. Clinical results with Circassia's allergy T-cell vaccines show that short treatment regimes can greatly reduce patients' allergic reactions, without the need for adjuvants or other immune stimulators, while proving extremely well tolerated. Source: PRNewswire 11/18/10

PARP Inhibitor Shows Antitumor Activity in First Trial in Humans

A new drug that targets proteins responsible for helping cancer cells to repair damage to their DNA has shown promising antitumor activity in its first trial in humans. Some patients with a range of solid tumors, many of whom had been treated unsuccessfully for their cancer with other therapies, have seen their tumors shrink or stabilise for periods of between 46 days to more than a year. The research was presented at the 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Berlin on November 18. Laboratory studies of the drug, MK-4827, have shown that it inhibits proteins called PARP1 and PARP2 (poly(ADP)-ribose polymerase). Tumors that are caused by a mutation in the BRCA1 or BRCA2 genes are susceptible to cell death through PARP inhibition because correctly functioning BRCA genes assist in repairing double-strand DNA breaks via a process called homologous-recombination-dependent DNA repair, whereas mutated versions are unable to perform this role. Normal cells do not replicate as often as cancer cells, and they still have homologous repair operating; this enables them to survive the inhibition of PARP and makes PARP a good target for anticancer therapy. In a Phase I trial conducted at the H. Lee Moffitt Cancer Center (Tampa, Fla.), University of Wisconsin-Madison, and the Royal Marsden Hospital (London, U.K.), MK-4827 was given to 59 patients with a range of solid tumors. Some patients had cancers caused by mutations in the BRCA1/2 genes, such as breast and ovarian cancer, but others had cancers that had arisen sporadically. The drug was given in pill form once a day, and the researchers found that the maximum tolerated dose was 300 mg a day. The researchers saw antitumor responses in both sporadic and BRCA1/2 mutation-associated cancers. Ten patients with breast and ovarian cancers had partial responses, with progression-free survival between 51 and 445 days, and seven of these patients are still responding to treatment. Four patients (two with ovarian cancer and two with nonsmall-cell lung cancer) had stable disease for between 130 and 353 days. Patients are being recruited for additional studies and an expansion of the existing trial. MK-4827 is also being studied in combination with conventional chemotherapy drugs. Source: EurekAlert! 11/17/10

Company Finalizes Phase III Development Program for Breast Cancer Treatment

After recent consultation with the U.S. Food and Drug Administration (FDA), Merrion Pharmaceuticals in Ireland is preparing for a Phase III study for Orazol™ that could commence in 2011. If successful, the study will allow a new drug application for Orazol to be made under the FDA’s abbreviated approval procedure section 505(b)(2) using a single Phase III study. The study will compare Orazol against placebo as an adjuvant breast cancer treatment with a primary endpoint of disease-free survival. The company hopes to market the product for use in combination with existing treatments for early-stage breast cancer patients, and also has been focused on gaining approval for an oral form of this drug (zoledronic acid) for a bone metastases indication in Europe. Orazol has shown several benefits over current infusion therapy in Phase II research for bone metastases. Source: Merrion Pharmaceuticals 11/16/10

Enrollment and Dosing Suspended in Lupus Trial to Address Reports of Vial Problems

Anthera Pharmaceuticals, Inc. in November announced that it has notified the U.S. Food and Drug Administration that the company has placed a voluntary hold on PEARL-SC, the Phase IIb study of A-623 for the treatment of systemic lupus erythematosus (lupus), due to problems found with product vials. The company was recently notified by a single clinical investigator that a number of vials of clinical product had experienced cracking. After a preliminary inspection of selected product inventory at the site and at a product storage facility, the company determined that the single site finding was not an isolated problem. As a result of these findings, patient enrollment in the study was immediately suspended and patients currently enrolled in the study will discontinue dosing while the company conducts a complete analysis of the problem. There have been no reports of patient-related side effects or problems with drug administration that could be attributed to this problem and, to date, no serious adverse events have been reported to the company in the trial. Source: PRNewswire 11/16/10

Phase II Data in Children with Cystic Fibrosis Shows Promise for Drug

PTC Therapeutics, Inc. in November announced the publication of data from a Phase IIa clinical trial of ataluren in children with nonsense mutation cystic fibrosis (nmCF) in the American Journal of Respiratory and Critical Care Medicine. The published data show that treatment with ataluren, an investigational new drug, resulted in statistically significant improvements in the production and function of cystic fibrosis transmembrane conductance regulator (CFTR), a critical protein lacking in CF patients. The randomized dose-ranging study was designed to evaluate the safety and activity of two ataluren doses in children with nmCF. The study enrolled 30 participants aged 6 to 18 years at three trial sites in Belgium and France. Patients were assessed in two 28-day cycles, comprising 14 days on and 14 days off ataluren. Patients received a dose of 4-, 4-, 8-mg/kg in one cycle and a dose of 10-, 10-, 20-mg/kg in another cycle, in a randomized order. The primary endpoint was CFTR chloride transport as assessed by nasal transepithelial potential difference (TEPD), a surrogate for the presence and activity of the CFTR protein. Results showed that ataluren induced statistically significant improvements in chloride channel activity, with some patients achieving chloride transport values in the range of healthy children. Overall, 50 percent of patients had a total chloride transport response (at least a -5 mV improvement) and the mean change for all evaluable patients was -4.2 mV after two 28-day treatment cycles at two dose levels. Importantly, TEPD compliance was excellent with only one of 150 tests not completed suggesting repeated TEPD evaluations are feasible in children of this age group. The development of ataluren has been supported by grants from Cystic Fibrosis Foundation Therapeutics Inc.; the U.S. Food and Drug Administration's Office of Orphan Products Development; Muscular Dystrophy Association; National Center for Research Resources; National Heart, Lung, and Blood Institute; and Parent Project Muscular Dystrophy. 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 11/15/10

Primary Endpoint Acheived in Pivotal Bridge-to-Transplant Trial

HeartWare International, Inc. in November announced that data from its pivotal bridge to heart transplantation study, ADVANCE, showed that 92 percent of the investigational device patients met the per protocol primary endpoint of the trial, which was defined as alive on the originally implanted device, transplanted or explanted for recovery at 180 days. Results from the clinical study also demonstrated that 94 percent of the investigational device patients enrolled in the study achieved a survival endpoint at 180 days, and the study projected one-year survival of 91 percent. HeartWare's ADVANCE trial is 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. Between August 2008 and February 2010, 140 patients at 30 hospitals in the United States received the HeartWare investigational device. The per protocol analysis includes 137 patients in the investigational device cohort. Results for the comparator arm of the study, derived from 499 contemporaneous patients from the Interagency Registry for Mechanically Assisted Circulatory Support, demonstrated 90 percent success of the primary endpoint at 180 days, as well as survival at 180 days of 90 percent, and 86 percent at 360 days. Based on these results for the primary endpoint of the ADVANCE study, noninferiority of the investigational device was established. Compared to baseline, HeartWare patients were able to walk 113 meters farther in six minutes when tested three months after surgery, and patient assessment of their own quality of life more than doubled. The final implant in ADVANCE was performed in February 2010, and the last follow-up evaluation at 180 days was in August. Through a Continued Access Protocol granted by the FDA, an additional 75 patients have been implanted in the ADVANCE clinical study. HeartWare anticipates submission to the FDA of a Premarket Approval application seeking approval of the HeartWare System for the bridge to transplant indication in December of this year. HeartWare also is recruiting 50 U.S. sites for a 450-patient destination therapy study using the system. Source: PRNewswire 11/14/10

RVVC Vaccine Demonstrates Safety and Immunogenicity in Phase I

Pevion Biotech AG in November announced positive preliminary results from a Phase I study of PEV7, the first vaccine against recurrent vulvovaginal candidiasis (RVVC). Also known as chronic recurrent thrush, RVVC is a highly debilitating condition