Clinical Trial Updates

Phase III Trial Initiated for the Treatment of Alzheimer's Disease

Baxter Healthcare Corp. in September announced initiation of a Phase III clinical trial following U.S. Food and Drug Administration review of its investigational new drug application to evaluate Gammagard Liquid [Immune Globulin Intravenous (IGIV)], marketed as Kiovig in the European Union, for the treatment of mild-to-moderate Alzheimer's disease. This trial is expected to be the first of two pivotal Phase III trials required to support filing for regulatory approval of the product as a potential treatment for the disease. The prospective, 18-month, randomized, double-blind, placebo-controlled, two dose-arm, parallel study will focus on 360 subjects of both genders, ages 50 to 89 years old, with dementia of mild-to-moderate severity. The study will determine whether Gammagard Liquid treatment results in a significantly slower rate of decline of cognitive and other functions compared to placebo. Approximately 40 U.S. leading academic centers have been identified and will begin clinical trial enrollment within the next several weeks. The trial is partially funded by the National Institutes of Health through the Alzheimer's Disease Cooperative Study, a cooperative agreement between the National Institute of Aging and the University of California San Diego. Source: PRNewswire 9/22/08

FDA Grants Orphan Drug Designation for Hypophosphatasia Product Candidate

Enobia Pharma announced in September that it has received Orphan Drug designation from the U.S. Food and Drug Administration (FDA) for ENB-0040, its enzyme replacement therapy for hypophosphatasia, a rare, life-threatening genetic bone disease. In August, Enobia dosed the first patient in a Phase I clinical trial of ENB-0040. Hypophosphatasia can be fatal in infants and cause serious disability in older patients; it has no currently approved FDA treatment. Patients have low levels of the tissue nonspecific form of alkaline phosphatase, an important regulator of bone mineralization, leading to rickets in infants and children and osteomalacia ("soft bones" resulting from poor mineralization) in adults. ENB-0040 is a fusion protein that includes the catalytic domain of human tissue nonspecific alkaline phosphatase, an immunoglobulin Fc domain, and a patented anionic peptide used to target the enzyme to bone. Preclinical studies of ENB-0040 in the "knockout" mouse model of severe hypophosphatasia were recently published in the Journal of Bone and Mineral Research and showed that subcutaneous administration of ENB-0040 significantly improved survival and prevented the skeletal and dental manifestations of the disease. Source: PRNewswire 9/19/08

Phase I/II Trial Initiated to Evaluate Prodrug for Soft Tissue Sarcoma

Threshold Pharmaceuticals, Inc. in September announced that it has initiated a Phase I/II clinical trial of TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma. TH-302 is a proprietary hypoxia-activated prodrug that specifically targets tumor hypoxia. Approximately 36 patients with metastatic and/or advanced unresectable soft tissue sarcoma are planned to enroll in the clinical trial at various sites in the United States. The dose escalation phase of the trial will enroll up to 24 patients. The primary objective of the dose escalation component of the study is to establish the maximum tolerated dose and dose limiting toxicities of TH-302 in combination with doxorubicin. Patients for whom no effective therapy is available, or for whom monotherapy with doxorubicin is considered standard therapy, are eligible for the trial. Patients who successfully complete one treatment cycle without evidence of significant treatment-related toxicity or progressive disease may continue to receive treatment for up to six cycles. Once the maximum tolerated dose has been reached, the Phase II portion of the trial will enroll an additional 12 patients at that dose. The primary objective of the dose expansion component of the study is to make a preliminary assessment of the efficacy of TH-302 in combination with doxorubicin as measured by the progression-free rate at six months in patients previously untreated with chemotherapy. The secondary endpoints of the trial include response, duration of response, progression-free rate at three months, progression-free survival, overall survival, and various safety parameters. Tumor response will be evaluated at baseline and every six weeks using the Response Evaluation Criteria In Solid Tumors (RECIST). Source: Globe Newswire 9/16/08

Enrollment Milestone Reached in Phase III Oral Insulin Spray Trial

Generex Biotechnology Corp. has reached the enrollment milestone of more than 200 subjects in its pivotal Phase III clinical trial of Generex Oral-lyn™, its flagship proprietary prandial oral insulin spray product. There are 74 sites in the United States, Canada, Bulgaria, Poland, Romania, Russia, and Ukraine actively screening and enrolling subjects. The study will involve up to 750 subjects with type 1 diabetes mellitus with the objective of comparing the long-term efficacy of Generex Oral-lyn and the company's RapidMist™ Diabetes Management System with prandial injections of regular human insulin as measured by HbA1c. The company believes that Generex Oral-lyn will offer a safe, simple, fast, effective, and pain-free alternative to prandial insulin injections, which will improve subject compliance with therapeutic regimes, thereby delaying the progress of diabetes and the onset of its myriad complications. Generex Oral-lyn is presently approved for commercial sale in India and Ecuador. Source: Globe Newswire 9/16/08

Positive Data Reported from Phase III Study of Insulin System in Type 1 Diabetes

MannKind Corp. in September released preliminary top-line results from a 52-week, Phase III clinical study of the Technosphere® Insulin System in patients with type 1 diabetes (Study 009). This study compared the safety and efficacy of prandial inhalations of Technosphere Insulin versus prandial subcutaneous injections of insulin aspart (the comparator group). Both groups also received daily subcutaneous injections of a basal insulin (insulin glargine). A total of 565 patients were studied in sites in the United States, Europe, and Latin America. A total of 293 patients received Technosphere Insulin, and 272 patients received insulin aspart. Technosphere Insulin, compared to a rapid-acting insulin analog, showed comparable reductions in A1C levels, comparable numbers of patients reaching predefined A1C goals, superior fasting blood glucose levels, better early postprandial glucose control, fewer patients experiencing hypoglycemic events, weight loss versus weight gain, and no adverse effects on pulmonary function. A company spokesperson said that the next step is to lock the databases for the remaining two pivotal studies, which further examine long-term efficacy and safety in patients with diabetes. The company also is continuing its preparations to submit a new drug application by year-end or shortly thereafter. Source: PRNewswire 9/16/08

Drug Yields Statistically Significant Improvement in Sleep Disturbance from Hot Flashes

Bionovo, Inc. in September announced that its lead drug candidate, MF101, for menopausal hot flashes, showed improved sleep quality for women in a Phase II study completed earlier this year. The company previously announced that the study showed positive results in the trial for the primary endpoint of reducing the number of hot flashes when compared to placebo. Additional analyses from the trial now show that MF101 reduced the number of times women were woken up from sleep due to hot flashes, also known as "night awakenings" or "night sweats." The median percent reduction in night time awakenings from hot flashes for women randomized to the higher dose of MF101 was 67 percent, and this reduction was statistically superior compared to the placebo. Women randomized to the lower dose of MF101 also had a greater reduction of night time awakenings due to hot flashes compared to placebo (58 percent versus 44 percent). Trial recruitment took place at six medical centers in the United States: University of California San Francisco, University of Minnesota, University of Pittsburgh, University of Tennessee, University of Alabama, and the San Diego Medical Center for Clinical Research. Two hundred and seventeen women were enrolled in the multicenter, double-blind, placebo-controlled, randomized trial. Postmenopausal women with 50 or more moderate to severe hot flashes per week were randomized to one of three treatment groups receiving one of two doses of MF101 or placebo for 12 weeks. MF101 is an estrogen receptor beta selective drug developed as an alternative to postmenopausal hormone products currently on the market. Source: PRNewswire 9/15/08

Pivotal Trial Uses Radiology Treatment to Bust Blood Clots in Legs

ATTRACT--the first major national trial of a catheter-based treatment for deep vein thrombosis (DVT)--will evaluate the use of clot-dissolving drugs in combination with clot removal devices to prevent post-thrombotic syndrome (PTS) in patients with DVT (the formation of a blood clot in a leg vein). The outcomes of this pivotal multicenter trial--to be funded at more than $10 million by the National Institutes of Health's National Heart, Lung, and Blood Institute--are likely to change the way DVT is treated in the United States. Early treatment of DVT with blood thinners is important to prevent a life-threatening pulmonary embolism, but blood thinners do not dissolve the existing clot, which remains in the leg. While many patients' clots will slowly dissolve over time, often the vein wall and vein valves become irreversibly damaged in the process. The radomized ATTRACT trial will begin later this year. It will assess the presence and severity of PTS, quality of life, relief of pain and swelling, safety, and costs. At least 28 U.S. clinical centers will enroll 692 patients and monitor their health for two years. Source: EurekAlert! 9/15/08

Ovarian Cancer Drug Trial Reveals Promising New Treatment

Women with recurrent ovarian cancer can be helped by an experimental therapy using a drug already touted for its ability to fight other cancers, a finding that provides hope for improved treatment of this deadly disease. Dr. Bradley Monk, a University of California (UC) at Irvine gynecologic oncologist who led the worldwide Phase III clinical trial, said trabectedin is the most recent addition to a short list of active drug therapies for recurrent ovarian cancer. He presented study results in September at the 33rd Congress of the European Society for Medical Oncology in Stockholm. "These are exciting results because positive trials in recurrent ovarian cancer are rare and have almost always led to federally approved treatments," said Monk, an associate professor who studies and treats ovarian cancers at the Chao Family Comprehensive Cancer Center at UC Irvine. In the trial, an international group of researchers treated 672 women whose ovarian cancer had progressed after first-line treatment. Half the women received a combination therapy of trabectedin and a chemotherapy drug called pegylated liposomal doxorubicin. The other half received the chemotherapy drug alone, which is standard treatment in these cases. In patients on the combination therapy, researchers found no progression of the cancer for an average of 7.3 months, as compared to 5.8 months for those treated with the single drug. For those who had relapsed more than six months after the first-line therapy, the median progression-free time was 9.2 months for the combination treatment, as compared to 7.5 months for the other patients. Under the brand name Yondelis, trabectedin is approved in Europe and South Korea for treating advanced soft tissue sarcoma. In addition to the Phase III ovarian cancer trial, it is being studied in smaller Phase II trials for prostate, breast, and pediatric cancers. Source: EurekAlert! 9/15/08 For more information from the European Society for Medical Oncology, click here.

Long-Term Data Continue to Show Improvement in Survival of Brain Cancer Patients

Northwest Biotherapeutics, Inc. in September announced the most recent long-term follow-up data, through June 15, 2008, from its prior Phase I and Phase I/II clinical trials with DCVax®-Brain, which began in 2000 and 2003, for patients with glioblastoma multiforme, the most lethal type of brain cancer. This long-term data shows that 84 percent of patients who received DCVax-Brain in these trials have so far lived longer than the median survival of 14.6 months under standard of care; 68 percent have lived more than two years, 58 percent more than 30 months, 42 percent more than three years, and 26 percent more than four years. Some patients have survived as long as eight years to date. The median survival in the patients from these trials is now 36.4 months. DCVax-Brain is a personalized vaccine that takes a patient's own immune cells and trains them in the laboratory to attack the biomarkers from that patient's own tumor cells. The 10-day manufacturing process produces several years of personalized vaccine for a patient, making DCVax-Brain an "off-the-shelf" product for that patient throughout the treatment period that is administered as a simple injection under the skin, similar to a flu shot, and is not toxic as chemotherapies are. The long-term data from these clinical trials shows that more than 80 percent of the patients who received DCVax-Brain showed a clinical response. In contrast, the typical response rates for cancer drugs are in the range of 20 to 25 percent, and have been as low as 13 percent with some approved cancer drugs. DCVax-Brain is now in a large Phase II clinical trial designed and powered as a pivotal trial, which is currently enrolling patients at 11 medical centers across the U.S. Source: PRNewswire 9/11/08

Positive Results from Phase II Study of Patch for Acute Pain

Cerimon Pharmaceuticals, Inc. announced positive results in September from a Phase II clinical study of its once-daily, topical 15 mg (1 percent) diclofenac sodium patch. The multicenter SUPPORT (Stop Underlying Pain with a diclofenac Patch and Obtain Relief Topically) study evaluated the safety and efficacy of the company's patch in 170 subjects with pain due to acute, mild-to-moderate ankle sprains. The study achieved statistical significance in its primary efficacy endpoint, demonstrating treatment with diclofenac sodium patch resulted in greater improvements in average pain during daily activities compared to placebo at day three. The study also achieved statistical significance for several secondary endpoints, including improvement in pain at day seven and the percentage of individuals who achieved a reduction from baseline pain by greater than 50 percent and 70 percent at day three. The subjects treated with the diclofenac patch used fewer doses of rescue medication (acetaminophen) as well. In the randomized, double-blind, parallel group, placebo-controlled study, half of the subjects received the topical diclofenac patch and the other half received a placebo patch. The diclofenac patch is designed to offer once-daily, site-specific pain relief without the systemic side effects associated with oral NSAIDs, and with superior skin penetration, optimal adhesiveness, and better feel and flexibility than other topical pain patches currently available or in development. Based on the results of the SUPPORT study, Cerimon intends to initiate its Phase III program of the diclofenac patch by early 2009. Source: PRNewswire 9/11/08

Final Patient Completes Phase III Clinical Trial of Treatment for Fibromyalgia

Jazz Pharmaceuticals, Inc. in September announced that the final patient has completed participation in the first Phase III pivotal clinical trial of JZP-6 (sodium oxybate) for the treatment of fibromyalgia. The clinical program includes two randomized, double blind, placebo-controlled studies. The first study enrolled 550 fibromyalgia patients at 65 centers in the U.S. The second Phase III study is enrolling patients at sites in the U.S. and Europe. The primary endpoint for both studies is the change from baseline in pain based on the pain visual analog scale, which the U.S. Food and Drug Administration (FDA) and the European Medicines Agency have indicated is the appropriate primary endpoint. The first trial's results remain blinded to the company, investigators, and patients as the company analyzes the extensive data set generated by this study. Jazz anticipates releasing primary efficacy and safety data from the trial on schedule in the fourth quarter of this year, and continues to plan for submission of a New Drug Application to the FDA by the end of 2009. The JZP-6 clinical program also includes an open-label continuation trial to provide long-term safety data. Enrollment in this trial is ongoing, and the trial is open to patients who complete either of the two pivotal Phase III trials. Sodium oxybate is the active ingredient in Xyrem®, a Jazz Pharmaceuticals product approved by the FDA for the treatment of excessive daytime sleepiness and cataplexy (the sudden loss of muscle tone) in patients with narcolepsy. Sodium oxybate has not been approved for the treatment of fibromyalgia. Source: PRNewswire 9/11/08

Successful Phase II Results Achieved with Technology for Cat Allergies

Circassia Ltd in September announced positive results from a Phase II clinical study of its anti-allergy technology, ToleroMune®, in the field of cat allergy. The trial showed that ToleroMune treatment can substantially reduce allergic reactions to the allergen that causes most cat allergies, and importantly was well tolerated by all patients. Circassia conducted the double-blind study in Germany, where patients with a confirmed history of cat allergies received a single dose of ToleroMune therapy or placebo. The 88 study participants were divided into groups, with each receiving a different dose, either via subcutaneous or intradermal injection to compare the two routes of administration. To test the effect of the treatment, patients received a microscopic dose of cat dander (the main allergen responsible for cat allergies) into their skin several weeks later. Patients who received ToleroMune therapy via the most effective administration route had markedly reduced skin reactions to the cat allergen at all of the five dose levels tested compared to placebo. The most effective dose reduced reactions by more than 40 percent, compared to 10 percent for placebo. Throughout the study, the ToleroMune treatment proved well tolerated, with no serious or severe adverse events experienced in any of the groups, despite the steadily increasing doses. The company aims to build on the trial's results by testing short treatments of several doses in future trials. Source: PRNewswire 9/10/08

Five New Studies Demonstrate Clinical Experience for Diabetes Treatment

New data analyses presented at the 44th Annual Meeting of the European Association for the Study of Diabetes showed initial combination therapy with the dipeptidyl peptidase-4 inhibitor, Januvia™ (sitagliptin), and metformin provided improvements in blood sugar levels (as measured by A1Ci) over two years of treatment and was generally well tolerated. Also presented at the meeting was a separate, new pooled analysis of 6,139 patients that showed that Januvia was generally well tolerated in clinical trials up to two years in duration. In other studies, the addition of Januvia to the combination of metformin and rosiglitazone significantly improved blood sugar control; a 52-week trial of Japanese patients with an investigational dosing regimen demonstrated that treatment with Januvia added to ongoing pioglitazone therapy also provided significant glucose lowering; and an additional analysis demonstrated that in patients with type 2 diabetes, Januvia provided glycemic control regardless of baseline characteristics of age, gender, BMI, HOMA-ß, and P/I ratio. The Merck & Co. product is indicated, as an adjunct to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes, and has received approval in 80 countries. Source: EurekAlert! 9/9/08

Clinical Trials Under Way to See if Light Can Make Toenails Look Better

Is it possible to use the healing power of light to treat infections? As it tries to answer this question, Keraderm in September announced full enrollment for pivotal trials to obtain U.S. Food and Drug Administration clearance of its phototherapy treatment for onychomycosis (fungal nail infections). Eighty-five subjects with confirmed onychomycosis have been enrolled in the prospective, placebo-controlled, double-blind, multisite trial. Study objectives include assessing safety, clinical improvement, mycological cure, and visual improvement of the treated nail. Patients will receive four 20-minute treatments over a four-week period, and will be followed up to assess safety and efficacy of the treatments after several months. Keraderm's germicidal light technology has been clinically shown to successfully inactivate the organisms that cause onychomycosis. The results of Keraderm's collaboration with the Wellman Center for Photomedicine on a grant from the National Institutes of Health have recently been published in the British Journal of Dermatology. The data indicate that Keraderm's treatment is effective at penetrating the nail and also inactivating the organisms that cause onychomycosis. Additionally, results of Keraderm's successful pilot clinical trials at Brigham and Women's Hospital have been presented at the 2007 World Congress of Dermatology Conference and the 2008 American Academy of Dermatology Conference. These pilot clinical trials indicated significant improvement in 73 percent of subjects treated with its proprietary technology with no significant side effects. Keraderm anticipates an increased improvement rate in the current pivotal trials due to further enhancements of its technology. Source: PRNewswire 9/9/08

Phase II Results Show Promise for Acute Migraine Product

CoLucid Pharmaceuticals, Inc. has announced that Phase II results for its lead compound COL-144 demonstrated the product's safety and effectiveness in relieving acute migraine headaches. COL-144 is a first-in-class Neurally Acting Anti-Migraine Agent, which unlike triptans, exhibits antimigraine activity without causing vasoconstriction. COL-144 is a highly potent and selective 5HT1F receptor agonist. Results presented in poster presentations at the European Headache and Migraine Trust International Congress 2008 in London in September showed that the majority of patients experienced migraine relief 20 to 40 minutes after dosing and COL-144 was generally well tolerated. The randomized, double-blind study evaluated 130 migraine patients. Patients were not on prophylaxis and received 2.5 to 45 mg of COL-144 or placebo as an intravenous infusion over 20 minutes as first-line treatment of an acute migraine attack. The primary endpoint parameter was headache response, defined as a reduction in headache severity from moderate to severe at baseline to mild or no headache at two hours after initiation of infusion of study drug. A higher proportion of patients showed a headache response at two hours post dose in the 10 mg, 20 mg, 30 mg, and 45 mg groups compared to placebo (54.2 to 75 percent versus 45.2 percent) with a statistically significant linear association between response rates and dose levels. The adaptive study design used could identify doses giving a headache response in 50 to 75 percent of patients. It did not explore the maximum possible efficacy of the drug. Source: PRNewswire 9/6/08

Second Pivotal Phase III Trial in Cystic Fibrosis Begins

Pharmaxis announced in September that it has enrolled the first subject into its second pivotal Phase III clinical trial evaluating Bronchitol in cystic fibrosis sufferers. The trial is being conducted in 41 hospitals across North America, Argentina, and Germany, and is the final clinical step before Pharmaxis seeks approval to market Bronchitol for cystic fibrosis in the United States. This trial follows the recent closure to recruitment of the first Phase III trial involving 325 subjects. Bronchitol has been awarded fast-track status in the U.S., and orphan drug designation in both the U.S. and European Union. The trial is designed to include a 26-week efficacy treatment period, followed by a 26-week safety period. The efficacy component of the trial is a randomized, double-blind investigation of Bronchitol twice daily in approximately 300 patients with cystic fibrosis. The trial is enrolling cystic fibrosis patients aged six years and older. Participants will be assessed for improvements in lung function, infectious episodes, antibiotic use, quality of life, and a range of health economic measures. Pharmaxis is developing Bronchitol as a treatment to improve mucus clearance in the lungs of patients with cystic fibrosis, bronchiectasis, and chronic obstructive airway diseases. Bronchitol is a patented, inhalable dry powder formulation of mannitol that can be administered by a hand-held, pocket-sized device. Source: PRNewswire 9/4/08

Phase II Study Endpoints Achieved with Low-Dose Contraceptive Patch

Agile Therapeutics, Inc., announced in September that it successfully completed two key clinical trials in the development of the company's low-dose, once-weekly contraceptive patch, which the company refers to by its internal product code AG-200-15. The Phase IIb safety and efficacy study successfully met its primary endpoint of ovulation suppression, cycle control, and safety. The pharmacokinetic study demonstrated estrogen levels comparable with the well-established, low-dose oral contraceptive, LEVLEN®. There were no serious adverse events in either study. With the success of the studies, the company will discuss its Phase III plans for AG-200-15 with the Food and Drug Administration. The pharmacokinetic study was an open-label, randomized, comparative, single-center, two-period crossover study with 39 patients that evaluated two contraceptive patches to see if the systemic exposure of ethinyl estradiol (EE) and levonorgestrel (LNG) were comparable to LEVLEN. As intended, both the EE and LNG exposure over time of both patches were less than LEVLEN and consistent with the levels targeted by the company. In this multicenter, multicycle safety and efficacy study of 123 women, the company studied patches with different estrogen and progestin doses for three cycles to identify the regimen providing the best efficacy (as demonstrated by ovulation suppression), cycle control, and tolerability at the lowest hormonal dose. Topline results from the trial showed there was a clear dose response to ovulation suppression and cycle control. AG-200-15 provided the greatest ovulation suppression with the best cycle control of the three regimens studied. Source: PRNewswire 9/3/08

Treatment for Amyotrophic Lateral Sclerosis Enters Phase II

Sangamo BioSciences, Inc. announced in September that it has opened a Phase II clinical trial (SB-509-801) to evaluate its drug, SB-509, in subjects with amyotrophic lateral sclerosis (ALS), a progressive, degenerative motor-neuron disease for which there are limited treatment options and no cure. SB-509, is an injectable formulation of a plasmid encoding a zinc finger DNA-binding protein transcription factor (ZFP TF™) designed to upregulate the expression of the gene encoding vascular endothelial growth factor (VEGF-A). SB-509 is also in three additional Phase II clinical trials for diabetic neuropathy and stem cell mobilization. VEGF-A has been shown to have nerve protection properties as well as promoting nerve, blood vessel, and muscle growth. The SB-509-801 trial is a randomized, repeat-dosing, open-label, multicenter study designed to evaluate the effect of intramuscular administration of SB-509 on the progression of the disease in subjects with ALS. A total of 40 subjects with ALS will be enrolled in this trial and randomized into one of two treatment cohorts. The first cohort of 35 subjects will receive 60 mg of SB-509 in a divided dose into muscles in the arm, leg, and along the spine on both sides of the body. A second cohort of five subjects will receive 60 mg of SB-509 in a divided dose into the muscles in the lower limb in both legs. Each subject will receive a total of two treatments of 60 mg of SB-509 intramuscularly three months apart on Day 0 and Day 90. The study will be carried out over 11 months, including two months for screening, three months for two study treatments, and six months of follow-up after administration of the final dose. Source: PRNewswire 9/3/08

Phase III Trial Meets Primary Endpoint of Treating Acute Agitation in Schizophrenic Patients

Alexza Pharmaceuticals, Inc. in September announced positive results from its first Phase III clinical trial of AZ-004 (Staccato® loxapine) in schizophrenic patients with acute agitation. Both the 5 mg and 10 mg doses of AZ-004 met the primary endpoint of the trial, which was a statistically significant reduction in agitation from baseline to the two-hour post-dose time point, compared to placebo. AZ-004 is an inhalation product candidate being developed for the treatment of acute agitation in patients with schizophrenia or bipolar disorder. AZ-004 is being developed through Symphony Allegro, a product development partnership formed between Alexza and Symphony Capital, LLC. The trial enrolled 344 schizophrenic patients with acute agitation at 24 U.S. clinical centers. The trial was designed as an in-clinic, multicenter, randomized, double-blind, placebo-controlled study in which patients were eligible to receive up to three doses of study drug in a 24-hour period, depending on their clinical status. The primary endpoint for the study was the change from baseline in the PANSS (Positive and Negative Symptom Scale) Excited Component score (also known as PEC score), measured at two hours after the first dose. The key secondary endpoint was the Clinical Global Impression-Improvement (CGI-I) score, measured at two hours after the first dose. All results were considered statistically significant as compared to placebo, and all analyses were made on an intent-to-treat basis. Source: PRNewswire 9/2/08

Results of Dose Guiding Trial Support Further Study of Clotting Inhibitor

While the results of a recent study did not show a statistically significant difference in ischemic events among any of four doses of Bristol-Myers Squibb's apixaban evaluated, trends emerged that support further study, according to researchers at the Duke Clinical Research Institute. Apixaban targets the activity of Factor Xa, one of several enzymes involved in process of blood coagulation. Millions of patients worldwide take anticlotting drugs on a regular basis. Most are prescribed aspirin, clopidogrel (also known as Plavix or Iscover), and/or warfarin. Researchers studied the use of apixaban in 1,715 patients from 14 countries throughout Europe and North America who had suffered a recent heart attack. Roughly two-thirds of the patients had undergone angioplasty to clear blocked arteries and 99 percent of them were taking either aspirin or aspirin and clopidogrel. The study (called APPRAISE) was designed to identify the optimal dose of apixaban. Participants were randomized into one of four doses of apixaban or a placebo. Researchers tracked the incidence of bleeding and recurrent heart attack, stroke, chest pain requiring hospitalization or additional procedures, or death from cardiovascular problems for the following six months. At the end of the study, researchers discovered a nonstatistically significant trend suggesting that patients taking apixaban along with their regular treatment had a lower incidence of heart attack, stroke, chest pain, or death from cardiovascular problems than patients taking a placebo; but bleeding was an issue, especially among those taking the higher doses of the drug (10 mg twice daily or 20 mg once daily). Investigators discontinued those two arms of the study because patients were experiencing unacceptable rates of bleeding. Patients in the remaining arms of the study (2.5 mg twice daily or 10 mg once daily) also experienced more bleeding than those taking a placebo. Source: EurekAlert! 9//2/08

Drug Modestly Reduces Cardiovascular Events in Patients Unable to Tolerate ACE Inhibitors

The angiotensin-receptor blocker telmisartan should be regarded as a potential treatment for vascular disease or high-risk diabetes in the 20 percent of patients who are unable to tolerate the standard treatment of angiotensin-converting enzyme inhibitors. These are the conclusions of the TRANSCEND study, published early online and in an upcoming edition of The Lancet. This randomized, controlled trial analyzed 5,926 patients with vascular disease or high-risk diabetes and taking other proven therapies, of whom 2,954 received telmisartan 80 mg/day and 2,972 received placebo. The primary outcome of the trial was a combination of cardiovascular death, heart attack, stroke, or hospitalization for heart failure. Patients were followed up for a median of 56 months. The researchers found that mean blood pressure was lower in the telmisartan group than placebo by 4.0/2.2 mm Hg. The primary outcome was experienced by 465 (15.7 percent) patients given telmisartan compared to 504 (17 percent) in the placebo group, although the benefit for telmisartan was not statistically significant. One of the secondary outcomes—a combination of cardiovascular death, heart attack, or stroke—occurred in 384 (13 percent) of patients on telmisartan compared with 440 (14.8 percent) on placebo—a relative risk reduction of 13 percent for telmisartan patients, although this finding was of borderline statistical significance. A lower proportion of telmisartan patients (894/30.3 percent) were hospitalized for cardiovascular reasons than in the placebo group (980/33 percent): this result was statistically significant. Finally, fewer patients permanently discontinued medication in the telmisartan group (639/21.6 percent) than in the placebo group (705/23.8 percent) (borderline statistical significance). The most common reason for permanent discontinuation was symptoms of low blood pressure (hypotension) in both groups. Source: EurekAlert! 8/30/08

Positive Phase II Data Announced for Cancer Pain Product

Algeta ASA in August announced that the primary objective of its BC1-03 Phase II pain palliation study was met. The study showed that even single doses of Alpharadin in patients with painful bone metastases could produce increasing clinical benefit with increasing dose. The trial also confirmed Alpharadin's benign side-effect profile and, importantly for a drug in this clinical setting, no significant bone marrow toxicity was observed. The double-blind, randomized, pain control study compared the palliative effects of four different single-dose levels of Alpharadin in patients with bony metastatic hormone-refractory prostate cancer (HRPC). The drug was given by injection mainly on an outpatient basis. In addition to the palliative efficacy of Alpharadin, the study showed a dose-dependent reduction in bone alkaline phosphatase (ALP) ranging from no effect in the lowest dose group to a marked reduction in the higher dose groups. ALP is a severity marker of bony metastatic disease and of prognostic importance. The full results of the BC1-03 study will be submitted for publication in a peer-reviewed journal. Algeta has started enrolling patients for the pivotal Phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) study. This international study will evaluate Alpharadin in advanced HRPC that has metastasized to the skeleton. Approximately 750 patients are expected to be enrolled at more than 125 medical centers in Europe, Asia, South America, and Canada. Source: PRNewswire 8/28/08

Enrollment Completed in Second Phase III Trial for Systemic Lupus Erythematosus

Human Genome Sciences, Inc. (HGS) in August announced it has completed enrollment and initial dosing in BLISS-76, the second of two pivotal Phase III randomized clinical trials of LymphoStat-B® (belimumab) in patients with active systemic lupus erythematosus (SLE). Belimumab is being developed by HGS and GlaxoSmithKline under a codevelopment and commercialization agreement entered into in August 2006. With enrollment completed in both of the LymphoStat-B Phase III trials, the companies are on track to have data from the first trial by mid-2009, and data from the second trial by fall 2009. Assuming positive results, they anticipate filing a Biologic License Application with the FDA in the United States in the first half of 2010. BLISS-76 was initiated in February 2007, and has enrolled and randomized 826 patients at 133 clinical sites in 19 countries, primarily in North America and Europe. In April 2008, BLISS-52, the first of the two Phase III trials, completed the enrollment of 867 patients at 90 clinical sites in 13 countries, primarily in Asia, South America, and Eastern Europe. The BLISS studies are the largest double-blinded clinical trials ever conducted in lupus, and will evaluate the efficacy and safety of belimumab plus standard of care versus placebo plus standard of care in patients with serologically active SLE. The design of the two trials is similar, but the duration of therapy in the two studies is different—52 weeks for BLISS-52 and 76 weeks for BLISS-76. Belimumab is a human monoclonal antibody that specifically recognizes and inhibits the biological activity of B-lymphocyte stimulator. Source: PRNewswire 8/27/08

Favorable Results Seen from Phase I/IIa Pandemic Influenza Vaccine Program

Novavax, Inc. announced favorable results in August from the second stage of the Phase I/IIa human clinical trial of its pandemic influenza virus-like particle (VLP) vaccine candidate. The vaccine, which does not contain an adjuvant, induced robust neutralizing antibody responses. Novavax's VLP candidate is directed against the H5N1 A/Indonesia/05/2005 avian influenza strain. Avian influenza emerged in humans in Indonesia in 2005 and has caused 135 documented human cases, 81 percent of which have been fatal. In this study, the vaccine demonstrated strong neutralizing antibody titers across all three doses tested, exhibiting increasing antibody titers with the escalation of the dose. The study evaluated individuals who received two injections of 15 mcg, 45 mcg, 90 mcg, or placebo. Among those individuals in the 15 mcg arm, 72 percent had a neutralizing antibody titer of 1:20 or greater (four-fold rise from baseline) against the H5N1 A/Indonesia strain, as did 73 percent of subjects in the 45 mcg arm and 94 percent of subjects in the 90 mcg arm. Although the safety data are still blinded pending complete safety follow-up, there have been no serious adverse events reported. An independent external data and safety monitoring board fully supported continuation of the study, including expansion to the 90 mcg dose. These data are also supportive for moving forward with development of another Novavax vaccine candidate: against seasonal influenza. Dose ranging studies in healthy young adults and adults 65 years of age and older are scheduled to begin later this year. Source: PRNewswire 8/26/08

Wrinkle Product Examined in Phase II Study

Isolagen™, Inc. announced results in August from a prospective, open-label, Phase II study (IT-R-007) of Isolagen Therapy™ for the treatment of facial wrinkles and creases in approximately 40 subjects. Study subjects received two treatments of Isolagen Therapy in multiple facial regions approximately five weeks apart. At six months following their final treatment, 83 percent of subjects reported an improvement in their self-assessed score of the appearance of their wrinkles. This scale was the same as the one used in the recently completed Isolagen Therapy pivotal efficacy studies (IT-R-005 and -006). At the six-month time point, the results from an independent panel evaluation of study photographs also showed improvement in the appearance of wrinkles, with the independent panel scoring improvement in more than 75 percent of participants. Study IT-R-007 also included an assessment of skin quality of the study subjects, comparing results from baseline to the final six-month visit. Using a Skin Quality Assessment Tool developed for this study, 93 percent of subjects said their skin quality improved. Additionally, more than 95 percent of subjects showed improvements in skin quality based on the Treating Investigator Assessment. Conducted at five U.S. sites, the primary objectives of study IT-R-007 were to assess the safety and efficacy of the Isolagen Therapy. In this open-label study, all subjects received the Isolagen Therapy and there was no placebo control. The Isolagen Process™ is a proprietary cellular processing system that creates a natural, living cell therapy. By multiplying a person's own collagen-producing cells, or fibroblasts, into tens of millions of new cells, a personalized treatment is created that is then returned to the person's skin. Source: PRNewswire 8/25/08

Enrollment Completed in Phase III Microbicide Trial

Indevus Pharmaceuticals, Inc. in August announced the completion of enrollment in Protocol MDP 301, a Phase III clinical trial that began in October 2005 for PRO 2000, the company's candidate vaginal microbicide for the prevention of HIV and other sexually transmitted infections. The trial is sponsored by the United Kingdom's Medical Research Council and conducted by the Microbicides Development Programme, an international partnership of researchers established to develop microbicides for the prevention of HIV transmission. This trial enrolled 9,395 women at clinics in South Africa, Tanzania, Uganda, and Zambia. Results from this trial are expected to be available by the end of 2009. This is the second large trial testing the safety and effectiveness of the 0.5 percent dose of PRO 2000, and the largest trial of any microbicide to date. In July 2007, enrollment of 3,100 women was completed in Protocol HPTN 035, sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Results from the HPTN 035 trial are expected to be available by early 2009. Source: PRNewswire 8/22/08

Candidate for the Treatment of Gout Advances Into Phase I

Ardea Biosciences, Inc. in August announced that the Medicines and Healthcare products Regulatory Agency in the United Kingdom has authorized a Phase I study evaluating RDEA594 in normal healthy volunteers. RDEA594 is the company's lead product candidate for the treatment of gout. Earlier this year, the company initiated a Phase IIa proof-of-concept study of RDEA806, a prodrug of RDEA594, which should allow an early confirmation of RDEA594's activity in the target population of patients with gout. The randomized, double-blind, placebo-controlled trial will evaluate the safety, tolerability, pharmacokinetics, and uric acid-lowering effects of single ascending oral doses of RDEA594 in healthy adult male volunteers. RDEA594 is a major metabolite of RDEA806, Ardea's lead non-nucleoside reverse transcriptase inhibitor in clinical development for the treatment of HIV. RDEA594 does not have antiviral activity, and is believed to be responsible for the uric acid-lowering effects observed following administration of RDEA806 to more than 100 subjects in Phase I and Phase II clinical trials. In Phase I studies of RDEA806 in normal healthy volunteers, increased urinary excretion of uric acid was observed in the first 24 hours after dosing, with statistically significant, exposure-dependent decreases in serum uric acid of 35 to 50 percent observed during multiple dosing out to 14 days. Source: PRNewswire 8/21/08

Investigational Drug Shows Activity in Phase II Cystic Fibrosis Study

New Phase II data published this month in The Lancet show that treatment with the investigational oral drug PTC124 results in statistically significant improvements in the chloride channel function of patients with nonsense-mutation cystic fibrosis (CF). The study was conducted at the Hadassah Hebrew University Hospital in Jerusalem, Israel and sponsored by PTC Therapeutics. The study enrolled 23 adult patients (median age 25 years) with nonsense-mutation CF. More than 90 percent of patients had severe CF with compromised lung function, pulmonary infection with Pseudomonas or other pathogenic bacteria, and pancreatic insufficiency. Patients were assessed in two 14-day treatment courses of oral PTC124 therapy, the first given at a lower dose and the second given at a higher dose. Results showed that at both dose levels, treatment with PTC124 was associated with statistically significant improvements in CFTR-mediated chloride transport, with more than half of the patients entering the normal range during at least one treatment course. Improvements in lung function values and body weight were also observed. Based on these results, PTC intends to initiate a Phase IIb study later this year to evaluate the clinical benefit of PTC124 in adults and children with nonsense-mutation-mediated CF. Given the potential applicability of PTC124 to multiple genetic disorders, the company has a pivotal study of PTC124 for nonsense-mutation Duchenne/Becker muscular dystrophy ongoing, and is planning proof-of-concept studies in additional genetic disorders. Source: EurekAlert! 8/20/08

Clinical Testing Initiated for Enzyme Replacement Therapy to Treat Hypophosphatasia

Enobia Pharma in August announced that the first patient in its clinical program for hypophosphatasia has been dosed. Enobia is investigating enzyme replacement therapy with ENB-0040 for the treatment of this rare and often crippling genetic bone disorder for which there is no approved treatment. Under two separate protocols, ENB-0040 will be evaluated in both adults and infants afflicted with hypophosphatasia in Canada and the United States. Under the first protocol, safety, tolerability, and pharmacokinetics of ENB-0040 will be evaluated for one month in an open-label, dose-escalation Phase I study of ENB-0040 delivered intravenously and subcutaneously to six adults with hypophosphatasia at three North American sites. Under the second protocol, safety, tolerability, pharmacokinetics, and efficacy of ENB-0040 will also be evaluated in a six-month open-label study of up to six infants with particularly severe hypophosphatasia. Key efficacy outcomes include assessment of skeletal and respiratory manifestations of the disease. ENB-0040 is a fusion protein that includes the catalytic domain of human tissue nonspecific alkaline phosphatase and a patented peptide used to target the enzyme to bone. Source: PRNewswire 8/20/08

Company Receives Regulatory Clearance to Commence Study of Vaccine Candidate for Genital Herpes

BioVex Inc in August announced that the United Kingdom's Medicines and Healthcare products Regulatory Agency has accepted the company's application to conduct a Phase I clinical study testing the safety and immunogenicity of its lead infectious disease candidate for genital herpes, ImmunoVEX HSV2. The novel live-attenuated vaccine has been rationally designed to remove the genes that allow herpes virus to avoid the immune system. This should allow the immune system to recognize and mount a powerful immune response against the causative agent of genital herpes. In preclinical studies, ImmunoVEX HSV2 completely prevented all symptoms of genital herpes and triggered a powerful immune response, suggesting that ImmunoVEX HSV2 may be more potent than other HSV-2 vaccines for which data has been published. Meanwhile, BioVex is currently completing a Phase II clinical trial of OncoVEXGM-CSF for melanoma and Phase I/II clinical trials for head and neck cancer and pancreatic cancer. Earlier this year, the company announced that the FDA approved the design of a single, pivotal Phase III clinical trial evaluating OncoVEXGM-CSF in previously treated patients with metastatic melanoma under the Special Protocol Assessment (SPA) procedure and plans to make a second SPA submission for head and neck cancer later in the year. BioVex intends to begin its Phase III trial for OncoVEXGM-CSF in melanoma in the first quarter of 2009. Source: PRNewswire 8/20/08

Erectile Dysfunction Drug Also Shows Promise for Relief of Lower Urinary Tract Symptoms

Men with signs of benign prostatic hyperplasia (BPH) can be helped with a daily dose of erectile dysfunction drug tadalafil (Cialis®) to relieve associated lower urinary tract symptoms (LUTS), according to a new study published in the October issue of the Journal of Urology. Researchers from the University of Texas Southwestern Medical Center at Dallas, Northwestern University, and Lilly Research Laboratories report on a randomized, double-blind, placebo-controlled study of more than 1,000 men in 10 countries. Pathophysiology and treatment have shown a possible link between BPH LUTS and erectile dysfunction. PDE5 inhibitors like tadalafil have received increased attention for treating BPH LUTS, although they are currently only approved for erectile dysfunction. Participants in the tadalafil study were required to have at least a six-month history of LUTS secondary to BPH. Subjects with a high PSA (more than 10 ng/ml) were excluded, as were subjects with other complicating conditions or conflicting drug treatments. Anyone who had undergone treatment for erectile dysfunction or other BPH treatments underwent a four-week treatment-free screening period. All participants then received placebo for four weeks prior to randomization. The 1,056 subjects were then divided randomly into five groups that received a placebo or doses of 2.5, 5, 10, or 20 mg/day of tadalafil. Using the International Prostate Symptom Score, the researchers found that all doses of tadalafil were superior to placebo for relieving LUTS, with statistically significant effects at four, eight, and 12 weeks. Source: EurekAlert! 8/19/08

Enrollment Completed in Phase II Trial for Soft Tissue Sarcoma Treatment

Cell Therapeutics, Inc.'s subsidiary Systems Medicine announced in August that planned enrollment is complete in the European Organization for Research and Treatment of Cancer (EORTC) randomized Phase II clinical trial of brostallicin in patients with newly diagnosed advanced or metastatic soft tissue sarcoma who have had no prior chemotherapy. The primary endpoint of the trial is progression-free survival at six months. Patients are randomized in a 2:1 ratio either to receive brostallicin or the standard therapy, doxorubicin. The EORTC designed the study to enroll a total of 108 eligible and treated (evaluable) patients, and plans to conduct the final data analysis in early 2009. If the study results are encouraging, a Phase III study in soft tissue sarcoma could be initiated in 2009. In the Phase II study, a patient's tumor will be re-evaluated every six weeks during treatment, and at least four weeks after the first observation of a complete or partial response. After discontinuation of protocol treatment, patients who have not progressed will be re-evaluated every 12 weeks, unless they have started a new anticancer therapy. The primary endpoint is proportion of patients who are progression free at six months (26 weeks) after start of treatment according to RECIST. Secondary objectives are progression-free survival, objective tumor response based on RECIST, duration of response, and overall survival. Brostallicin, a novel synthetic second-generation DNA minor groove binder, has potent cancer killing activity and has demonstrated synergism in combination with standard cytotoxic agents, as well as with newer targeted therapies in preclinical experimental tumor models. More than 230 patients have been treated with brostallicin in single-agent and combination studies. Source: EurekAlert! 8/14/08

Phase I Study Launched to Study Inhibitor of C-Reactive Protein

Isis Pharmaceuticals, Inc. announced in August that it has initiated a Phase I study of ISIS 353512, an antisense drug that inhibits the production of C-reactive protein (CRP). CRP levels are frequently elevated in patients with a variety of diseases, including cardiovascular disease, Crohn's disease, rheumatoid arthritis, and end-stage renal disease. The blinded, randomized, placebo-controlled, dose-escalation study is designed to assess the safety and pharmacokinetic profile of ISIS 353512, as well as to assess the initial effects of the drug on baseline CRP levels in healthy volunteers. In addition, Isis is designing a broad Phase II program to investigate multiple indications for ISIS 353512. The company believes that CRP plays an important causal role not only in cardiovascular disease, but also in renal and inflammatory diseases. In preclinical studies, ISIS 353512 suppressed liver and serum CRP levels. Source: PRNewswire 8/13/08

Experimental Chemotherapy Regimen Shows Promise in Treating Advanced Lung Cancer

A combination of chemotherapy agents that have been tested in other tumor types appears to be a promising alternative to standard treatment for advanced non-small cell lung cancer, according to a report in the August 15 issue of Clinical Cancer Research. In a Phase II multicenter study of 56 patients with an advanced form of this common lung cancer, endpoints including response rate, progression-free survival, and overall survival from use of S-1 and irinotecan were similar to, or better than, those reported from standard treatment with platinum-based chemotherapy regimens. Because the study had only a single arm--meaning all patients received the experimental therapy--the researchers cannot say if this regimen offers more benefit than standard treatment, but they did report that side effects resulting from the experimental therapy appeared to be much less severe than those typically seen with standard treatment. A direct comparison between this experimental regimen and platinum-based "doublet" chemotherapy would have to be conducted to confirm what appears to be a survival benefit among patients who used S-1 and irinotecan. S-1 (also known as TS-1) is approved for use in Japan and Korea, where it has shown substantial benefit in treating gastric cancer, but is still in clinical trials elsewhere, including in the U.S. and Europe. Irinotecan, an intravenous drug originally developed and tested in Japan and approved for use in the U.S. in 1994, is most often used to treat colon cancer. Source: EurekAlert! 8/12/08

Prostatectomy Improves Outcome of Some Men with Prostate Cancer Over "Watchful Waiting"

Men with early prostate cancer who undergo radical prostatectomy have a lower rate of death due to prostate cancer than men who are followed without treatment, known as watchful waiting, according to a randomized, controlled trial published in the August 12 online issue of the Journal of the National Cancer Institute. The benefit from the surgery, with respect to prostate cancer death rates, remained constant beyond 10 years, but the overall death rates in the two groups were not statistically different. The applicability of the results to the current generation of prostate cancer patients is unclear, however, because few of the cancers treated in the trial were discovered by PSA (prostate-specific antigen) screening, a practice that is now widespread. The Scandinavian Prostate Cancer Group launched the current trial in 1989. In 2005, with a median follow-up 8.2 years, the researchers reported that men in the prostatectomy arm had lower rates of disease-specific mortality than those in the watchful waiting arm. The investigators were interested to know if the prostate cancer mortality difference would continue to increase with longer follow-up. Thus far, this is the only completed randomized trial comparing the two treatment options. Lars Holmberg, MD, of the Kings College Medical School in London, and colleagues from Finland and Sweden continued to follow the men for an additional three years. With a median follow-up of 10.8 years, the cumulative incidence rate for prostate cancer death was 13.5 percent in the surgery arm and 19.5 percent in the watchful waiting arm, for an absolute reduction of 6 percent. The benefit, in terms of absolute risk reduction, did not increase after the first 10 years following treatment. Source: EurekAlert! 8/12/08

Patient Enrollment Target Reached for Interim Analysis in Phase III Stroke Trials

Neurobiological Technologies, Inc. in August announced that enrollment into its two Phase III pivotal studies evaluating Viprinex™ (ancrod) for the treatment of acute ischemic stroke has reached the level of patients necessary to conduct a planned interim analysis across the two studies. The company is currently studying whether Viprinex is safe and effective for treating acute ischemic stroke when given within six hours of stroke onset. An independent data safety monitoring board (DSMB) will meet to review the efficacy data on an unblinded basis for the first time. In addition, the DSMB will evaluate the safety of Viprinex, as it has been doing since the start of the studies. Results of the interim analysis are expected in January 2009. The interim analysis will be based on the first 500 treated patients in the current trials who have completed their 90-day assessment. If the treatment effect observed for the ancrod patients is not better than that observed for the placebo patients, then the trials will be halted for futility, indicating that they are unlikely to demonstrate the benefit required for approval. If the trials are allowed to continue, the company will not have access to any unblinded patient data until the trials are completed. The primary endpoint of the trials is the modified Rankin Score, a measure of disability. Source: PRNewswire 8/12/08

Alzheimer's Disease Treatment Enters Human Clinical Trials

ProteoTech Inc. in August announced that it has completed regulatory Investigational New Drug requirements and has been cleared by the FDA to initiate its Phase I human clinical trial on Exebryl-1®, a novel small molecule drug targeting toxic beta-amyloid protein accumulation for the treatment of Alzheimer's disease. At the 2008 International Conference on Alzheimer's disease in Chicago, the company presented efficacy data in Alzheimer's transgenic mice, whereby Exebryl-1 lowered brain beta-amyloid protein load by greater than 30 to 50 percent, correlating with marked improvements in memory in these animals. Toxic and insoluble beta-amyloid protein accumulation is believed to be an important part of the disease progression and memory impairment observed in all patients with Alzheimer's disease. Data were also presented demonstrating oral bioavailability and blood-brain-barrier penetration of Exebryl-1. Initial studies suggest that the drug may also have an important dual capacity by inhibiting and reducing tau protein from forming paired helical filaments, which are important in neurofibrillary tangle formation. The presence of neurofibrillary tangles in brain containing tau protein is an important pathological hallmark of Alzheimer's disease. Further studies are ongoing to confirm these findings. Source: PRNewsire 8/7/08

Successful Phase IIa Clinical Trial of Oral Insulin Capsule Announced

Oramed Pharmaceuticals, Inc. in August announced successful results from the clinical trial of its oral insulin capsule, ORMD 0801. The trial demonstrated that the product had a good safety profile and was well tolerated and effective in lowering blood glucose levels in patients with Type 2 diabetes. The study was conducted at Hadassah University Medical Center in Jerusalem and was a continuation of the successful Phase Ib trials that Oramed completed earlier this year. This trial was the first to expose patients with Type 2 diabetes to ORMD 0801 and its primary goals were to assess the safety, tolerability, and pharmcodynamic effects in these patients. ORMD 0801 was well tolerated by all patients and had a good safety profile; no serious adverse events were encountered throughout the study. In six of the nine subjects analyzed, statistically significant reductions in glucose as well as C-peptide were observed. Source: PRNewswire 8/6/08

New Treatment Therapy Helps Inhibit Hepatitis C

Two new studies examine the use of Roche's nucleoside polymerase inhibitor, R1626, to the standard therapy for hepatitis C. The reports appear in the August issue of Hepatology. In the first study, a Phase IIa trial, it was shown that adding the treatment to standard therapy with pegylated interpheron alpha plus ribavirin leads to a synergistic antiviral effect. In the search for new and better treatments, researchers have been testing R1626, which previously has been used to inhibit HCV replication in vitro. The study group included 104 patients with HCV genotype 1--21 took 1,500 mg of R1626 twice a day along with peginterferon alpha-2a; 32 took 3,000 mg of R1626 twice a day along with peginterferon alpha-2a; 31 took 1,500 mg of R1626 twice a day along with peginterferon alpha-2a and ribavirin; and 20 took the standard-of-care treatment of peginterferon alpha-2a with ribavirin. After four weeks, HCV RNA was undetectable in 29 percent, 69 percent, and 74 percent of patients in the respective study arms, compared to 5 percent of patients receiving the standard-of-care treatment. A second study shows that, in patients with chronic hepatitis C, the antiviral activity increased with the dosage. Side effects were tolerable and there was no evidence of viral resistance. For 14 days, the patients were treated with R1626 orally at twice-daily doses of either 500 mg, 1,500 mg, 3,000 mg, 4,500 mg, or placebo. The study showed that R1626 was well tolerated up to 3,000 mg and there was no evidence of viral resistance in this study, perhaps reflecting the potency of R1626 as an antiviral agent. Source: EurekAlert! 7/31/08

Positive Top-Line Results Announced in Phase III Chronic Lymphocytic Leukemia Study

Genmab A/S and GlaxoSmithKline announced in July positive top-line results from an interim analysis of the Phase III pivotal study evaluating ofatumumab (HuMax-CD20®) to treat two groups of chronic lymphocytic leukemia (CLL) patients with high unmet medical need. At the interim analysis, the study met the primary endpoint in both populations and the results from the secondary endpoints also support the primary endpoint. The activity of ofatumumab was evaluated in 154 patients in this interim analysis, of whom 138 patients with refractory CLL were evaluable. About half of the patients (59) in the study were refractory to both fludarabine and alemtuzumab. The analysis also included a second group (79) of patients who were refractory to fludarabine and considered inappropriate candidates for alemtuzumab due to bulky tumor in their lymph nodes. An objective response rate of 51 percent consisting of 30 partial responses was achieved in the group of patients refractory to fludarabine and alemtuzumab. In the fludarabine refractory, alemtuzumab inappropriate patient group, an objective response rate of 44 percent was achieved, including one complete response and 34 partial responses. Achievement of the reported objective response rates was based on evaluations by an independent committee and are subject to review and confirmation by the regulatory authorities. A pre-Biologics License Application meeting has been requested with the FDA during which these data will be discussed with the potential of a 2008 filing. There is also the potential to submit to the European Union regulatory authorities in this time frame. The full data will be submitted for presentation to an academic meeting in due course. Source: PRNewswire 7/31/08

Final Data Released from Phase I Cervical Dysplasia Trial

Nventa Biopharmaceuticals Corp. in July announced that it has completed analysis of immunological data from all four cohorts of its Phase I clinical trial for HspE7, its lead product candidate. HspE7 is a therapeutic treatment for patients with cervical intraepithelial neoplasia, or CIN, a precursor to cervical cancer. The primary cause of CIN is infection with certain human papillomavirus (HPV) types, of which HPV16 is the most common. Based on an analysis of HPV16 E7-specific T-cell responses across all cohorts, Nventa has identified a dose regimen of 500 mcg of HspE7 and 1,000 to 2,000 mcg of Poly-ICLC, a toll-like receptor 3 (TLR3) adjuvant, for subsequent Phase II trials. The purpose of the Phase I trial was to determine the safety, tolerability, and immunogenicity of HspE7 plus escalating doses of adjuvant (50, 500, 1,000, and 2,000 mcg of Poly-ICLC). All dose regimens were found to be safe and well tolerated. Immunogenicity analysis demonstrated that the adjuvant potently enhanced HPV16 E7-specific T-cell responses in subjects who demonstrated no or low responses at baseline. Following discussions with, and input from, the FDA, Nventa has finalized its protocol for a multicenter, randomized, double-blind, placebo-controlled Phase II trial of HspE7 in patients with high-grade cervical dysplasia (CIN 2/3). Preparations have been made at approximately 40 clinical investigational sites in the U.S., Canada, and Latin America. The company has also designed a Phase II trial of HspE7 in patients with low-grade cervical dysplasia (CIN 1). Evaluation of clinical investigational sites in Europe and Latin America are under way. The company intends to initiate one or both of these Phase II trials once it has secured necessary financing. Source: PRNewswire 7/28/08

Significant Blood Pressure Reductions Seen Across Difficult-to-Treat Groups

New data show Exforge® (amlodipine and valsartan), a single-pill combination of the world's leading high blood pressure medicines Diovan® (valsartan) and amlodipine, gets nearly twice as many patients with high baseline blood pressure to a healthier blood pressure goal compared to amlodipine alone. Results of a study in patients with baseline systolic blood pressure greater than or equal to 160 mmHg published in The Journal of the American Society of Hypertension showed that 51.8 percent of patients on Exforge achieved systolic blood pressure control, defined as <140 mmHg at week four, compared to 27.7 percent of those on amlodipine alone. Systolic blood pressure, measured when the heart contracts and pumps, is an important indicator of a person's risk of cardiovascular events. The primary endpoint of the study was the change from baseline Mean Sitting Systolic Blood Pressure at week four. Results showed that on average, patients on Exforge experienced a significant 30.1 mmHg reduction in systolic blood pressure, compared to a 23.5 mmHg reduction in patients on amlodipine alone. In the same study, patients with systolic blood pressure greater than or equal to 180 mmHg treated with Exforge experienced significant systolic blood pressure reductions of up to 40.1 mmHg, compared with 31.7 mmHg for those treated with amlodipine alone. Exforge also demonstrated significantly better blood pressure-lowering efficacy than amlodipine alone across certain difficult-to-treat patient groups, including the elderly (over 65 years), obese people, and those with diabetes. The randomized, double-blind, multicenter, parallel-group study was carried out in 75 centers across Europe and the U.S. In total, 646 patients were randomized to receive treatment with Exforge (n=322) or amlodipine (n=324). Demographic and high blood pressure baseline characteristics were similar for both groups. Source: PRNewswire 7/28/08

Firm Announces Receipt of Not Approvable Letter From FDA

Vanda Pharmaceuticals Inc. in July announced the receipt of a not approvable letter from the U.S. Food and Drug Administration (FDA) in response to its New Drug Application for iloperidone, an investigational atypical antipsychotic that was reviewed for the treatment of schizophrenia. The FDA stated that Vanda had demonstrated the effectiveness of iloperidone at 24 mg/day in the 3101 study for which the company reported results in December 2006, and that the efficacy was similar to the active comparator, ziprasidone (Geodon®, Pfizer Inc.). In addition, the FDA stated that iloperidone was superior to placebo in patients with schizophrenia at doses of 12 to 16 mg/day and 20 to 24 mg/day in a prior study. However, the FDA expressed concern about the efficacy of iloperidone in patients with schizophrenia relative to the active comparator, risperidone (Risperdal®, Johnson & Johnson), used in prior studies. The FDA indicated that it would require an additional trial comparing iloperidone to placebo and including an active comparator such as olanzapine (Zyprexa®, Eli Lilly & Co.) or risperidone in patients with schizophrenia to demonstrate the compound's efficacy further. The FDA also stated that it would require Vanda to obtain additional safety data for patients at a dose range of 20 to 24 mg/day. Vanda has put on hold all iloperidone-related activities pending further review. Source: PRNewswire 7/28/08

Phase II Data are Encouraging for Onychomycosis Treatment

MacroChem Corp. in July announced results of a Phase II clinical trial involving 37 patients who completed a 48-week, U.S. multicenter, open-label efficacy and safety study of EcoNail, a topical antifungal lacquer for the treatment of onychomycosis (nail fungus). The composite primary efficacy endpoint of the trial was "complete cure," defined as negative mycology (negative fungal culture and negative KOH) and clear nail (as determined by expert panel review of clinical photographs). EcoNail is the company's patented, topically applied lacquer containing the antifungal econazole and MacroChem's enhancer SEPA®. A protocol-mandated, external expert panel assessed clinical photographs of patients who completed 48 weeks of EcoNail treatment. The panel observed that 24 patients (65 percent) showed evidence of clinical improvement, defined in the protocol as an increase in uninvolved (clear) nail area. While none of the 37 patients reached all criteria of the composite primary endpoint, the consensus judgment of the panel was that 15 of 37 patients (41 percent) demonstrated significant (greater than or equal to 25 percent) clinical improvement. All patients had fungal culture-proven nail infections at entry, but after 48 weeks of once-daily treatment with EcoNail, 100 percent of patients had cultures that were negative for dermatophyte growth. Eight of the 37 patients (22 percent) achieved the secondary endpoint of negative mycology (negative fugal culture plus negative KOH evaluation) at 48 weeks. Source: PRNewswire 7/24/08

Year-Long Safety Extension Study of Osteoarthritis Treatment Reveals No Surprises

NicOx S.A. in July announced the top-line results from the 52-week open-label safety extension study that was conducted following the completion of the 301 Phase III study for its osteoarthritis treatment, naproxcinod. The results revealed no unexpected safety findings, and efficacy was maintained for the one-year duration of the study, as measured by the patients' global assessment scale. In addition, the results showed that the patients' mean blood pressure was stable for 52 weeks following the completion of the 301 study, suggesting that naproxcinod does not increase blood pressure over time. Naproxcinod is NicOx' lead investigational drug and the first compound in the Cyclooxygenase-Inhibiting Nitric Oxide Donator class, which NicOx is developing for the treatment of the signs and symptoms of osteoarthritis. The 301 safety extension study was conducted in 92 clinical centers in the United States and enrolled the first 500 eligible patients with osteoarthritis of the knee who successfully completed the 301 Phase III study for naproxcinod. NicOx expects to announce the top-line efficacy results from the ongoing 302 and 303 pivotal Phase III studies for naproxcinod in the second half of 2008, ahead of a projected New Drug Application in mid-2009. Source: PRNewswire 7/24/08

Drug Provides Hope for Kidney Cancer Patients

Treatment with everolimus prolongs progression-free survival relative to placebo in patients with metastatic kidney cancer (renal cell carcinoma) who have experienced treatment failure on other regimens. These are the conclusions of authors of an article published early online and in an upcoming edition of The Lancet. Everolimus is an oral drug that inhibits an intracellular signalling pathway responsible for regulating cell metabolism, growth, and division. The recent advent of sunitinib and sorafenib has seen improved progression-free survival (PFS) and overall survival, but for the relatively new group of patients who have failed on these new treatments, there is a high unmet need for new therapies. Memorial Sloan-Kettering Cancer Center researchers conducted a randomized, controlled Phase III trial to test the efficacy of everolimus in these patients. Patients with metastatic kidney cancer whose disease had progressed on sunitinib, sorafenib, or both, were randomly assigned in a 2:1 ratio to receive everolimus 10 mg once daily (272 patients) or placebo (138), in conjunction with best supportive care. The primary endpoint was PFS, and the study was designed to end after 290 progression events. The researchers found that results of the second interim analysis showed a significant difference in efficacy favouring the everolimus arm; thus the trial was stopped after 191 progression events, as it was not ethical to continue without providing everolimus to all patients. Analysis showed that patients in the everolimus group were less than one third as likely to experience disease progression as those in the placebo group. Median PFS was more than twice as long in the everolimus group compared with placebo (4.0 versus 1.9 months). Source: EurekAlert! 7/22/08

First-in-Class Product Demonstrates Efficacy Against Liver Cancer and Associated Hepatitis B Virus

Jennerex, Inc. and its South Korean partner, Green Cross Corp., announced in July that novel findings from a Phase I clinical trial of its first-in-class lead product JX-594 demonstrated that the product was well-tolerated and resulted in clear anticancer efficacy in patients with liver cancer. Three patients with advanced treatment-refractory hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) were treated with JX-594. Objective radiographic responses were demonstrated. Serum tumor markers, which correlate with tumor burden over time in patients, decreased by up to 95 percent after treatment. JX-594 replication, its release into the circulation, and distant tumor targeting and infection were demonstrated. JX-594 administration resulted in tumor vascular shutdown. Oncolytic virotherapy was also shown, for the first time, to suppress underlying HBV replication in HCC patients by more than 50 percent in all three patients. The data were published in the journal Molecular Therapy. A Phase II clinical trial is now under way for JX-594 in liver cancer that is open in the U.S., and will shortly begin enrolling patients at sites in South Korea and Canada. JX-594 multiplies selectively within cancer cells, leading to their destruction. These newly created copies of JX-594 are then released and are able to infect and eradicate other tumor cells both locally and in distant sites in the body. This cycle of JX-594 replication, cancer cell destruction, release, and spread is then repeated. The poxvirus strain backbone of JX-594 has been used safely in millions of people as part of a worldwide vaccination program against smallpox. Source: PRNewswire 7/22/08

Company Defers Pivotal Study of Renal Protection System in the U.S.

PLC Systems Inc. announced in July that it will defer the commencement of the U.S. pivotal trial of its RenalGuard™ System in the prevention of contrast-induced nephropathy (CIN). The company continues to support the investigator-sponsored clinical trial now ongoing in Milan, Italy, as well as the limited market launch of RenalGuard in Europe, which began in the first quarter of this year, both of which are focused on the CIN prevention market. Mark R. Tauscher, president and CEO of PLC, said, "We are taking this action now because, while we have sufficient funds to commence the U.S. pivotal trial at this time, we believe we will be in a better position to successfully raise the funding necessary to complete the trial and prepare for U.S. market launch in the future, once we have the expected positive clinical data from the study currently under way in Italy.... In the meantime, we are continuing our dual commercialization strategy for RenalGuard. First and foremost, we are continuing to work with the U.S. Food and Drug Administration to secure a full approval of our RenalGuard study protocol so that we are well-positioned to start the trial with our targeted study sites." RenalGuard is designed to reduce the potentially toxic effects that contrast media can have on the kidneys when it is administered to patients undergoing image-guided procedures, such as those performed when placing drug-eluting stents. It is believed that allowing contrast media to dwell in the kidneys can lead to CIN. By inducing and maintaining a high urine flow rate before, during, and after these image-guided procedures, it is believed the incidence rates of CIN in at-risk patients can be reduced. RenalGuard facilitates this increased urine clearance enabling the body to more rapidly void the contrast media, thereby reducing its overall resident time and toxic effects in the kidney. Source: PRNewswire 7/21/08

Pivotal Trial Results Published for Alzheimer's Disease Treatment

Medivation, Inc. has announced publication of the results of its first Alzheimer's disease pivotal clinical trial of the investigational drug Dimebon in the July 19 issue of The Lancet. In this double-blind, placebo-controlled trial, patients with mild-to-moderate Alzheimer's disease treated with Dimebon experienced statistically significant improvements compared to placebo in all the key aspects of the disease: memory and thinking, activities of daily living, behavior, and overall function. At the end of 12 months, Dimebon-treated patients preserved their starting level of function on each measure of Alzheimer's disease. Additional analyses of the Dimebon pivotal study data presented at recent medical conferences showed that Dimebon's impact extended to caregivers. Behavioral improvements in Dimebon-treated patients resulted in a significant decrease in caregiver distress at six months and at one year compared to the distress of caregivers of placebo-treated patients. Further, after six months, caregivers of Dimebon-treated patients saved approximately one hour per day assisting patients with activities of daily living compared to caregivers of placebo-treated patients. In the trial, 183 patients with mild-to-moderate Alzheimer's disease were randomized to receive Dimebon (20 mg three times a day, administered orally) or placebo for six months; 134 patients continued treatment in a blinded manner for an additional six months (one year total treatment) in the same group to which they were originally randomized, and 120 of these patients (90 percent) completed the trial. Earlier this year, the U.S. Food and Drug Administration informed Medivation that this study can be used as one of the pivotal studies required to support the approval of Dimebon to treat mild-to-moderate Alzheimer's disease, as long as a significant proportion of the sites in the confirmatory Phase III trial are located in the United States. Source: PRNewswire 7/17/08

Breakthrough for Pandemic Influenza DNA Vaccines Announced

Vical Inc. in July announced a breakthrough with preliminary clinical trial data demonstrating that DNA vaccines can safely achieve significant immune responses against H5N1 pandemic influenza in humans. Preliminary human safety and immunogenicity data obtained in a 100-subject Phase I trial of the company's Vaxfectin®-formulated H5N1 pandemic influenza DNA vaccines demonstrated for the first time that DNA vaccines have achieved potentially protective levels of antibody responses in up to 67 percent of evaluable subjects in the higher dose cohorts. No significant safety issues were observed at any of the Vical vaccine doses tested. These results support further development of Vaxfectin-formulated DNA vaccines, and could position them as potential alternatives to conventional vaccines. The double-blind, placebo-controlled, dose-escalation trial was conducted in approximately 100 healthy volunteers age 18 to 45 at three U.S. clinical sites. The trial was designed to assess safety and immunogenicity following intramuscular vaccination with needle and syringe or with the Biojector® 2000 needle-free injection system in different cohorts, and to evaluate monovalent and trivalent Vaxfectin-formulated DNA vaccines at various doses. Preliminary results were presented at the IBC Life Sciences Next Generation Vaccines conference at National Harbor, Md., in July. Source: PRNewswire 7/17/08

Two Pivotal Diabetes Trials Completed and Interim Data Released

Biodel Inc. in July announced that its two pivotal Phase III VIAject™ clinical trials are complete, with the last study patient visit on July 14. Results of the full trial will be released either at Biodel's poster presentation at the European Association for the Study of Diabetes (EASD) on September 9 or at a later appropriate scientific forum. Biodel also announced that two abstracts containing interim data from its VIAject Phase III clinical trials were posted on the website for the 44th Annual Meeting of the EASD. The abstracts disclosed results of a January 2008 preliminary interim analysis of the secondary endpoints of dose, weight, and mild and moderate hypoglycemic events for the VIAject Phase III clinical trials. Results of the drug treatment were compared to the baseline for all patients who had completed six weeks or more of treatment. Additionally, total mild and moderate hypoglycemic events as of January 2008 were compared across the two treatment arms. The interim results demonstrated statistically significant differences in weight changes in patients with Type 1 and Type 2 diabetes using VIAject compared to Humulin® R in the first six weeks of the study. Biodel noted that the final data from these trials may differ from those suggested by the preliminary interim analysis. Furthermore the primary efficacy endpoint for the studies, change in HbA1c, has not been analyzed. Both HbA1c and incidences of severe hypoglycemic events will be analyzed and reported after the clinical trial database for the studies has been locked. VIAject is an ultra rapid-acting injectable human insulin intended for meal-time use by patients with Type 1 or Type 2 diabetes. In Phase I and Phase II clinical trials, VIAject has been shown to have a more rapid onset of activity than those reported for the existing rapid-acting insulin analogs. Source: PRNewswire 7/16/08

Prostate Cancer Treatment Enters Phase II Trial

Dendreon Corp. in July announced that it has initiated a Phase II trial of Provenge® (sipuleucel-T), an investigational active cellular immunotherapy for the treatment of prostate cancer, in men with localized prostate cancer who are scheduled to undergo a radical prostatectomy. The single-center trial called NeoACT (NEOadjuvant Active Cellular immunoTherapy), or P07-1, which is being conducted at University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, has begun enrolling approximately 40 patients. NeoACT is the first of two new Phase II trials of Provenge being initiated this year. Each patient will receive a complete course of active treatment over a one-month period beginning six to seven weeks prior to the patient's radical prostatectomy. Multiple safety and efficacy endpoints will be evaluated, including the immune response in the prostatectomy specimens and in the peripheral blood. Following radical prostatectomy, patients will be randomized to receive either a booster of Provenge or no booster. Given the evidence of a survival benefit seen in a previous Phase III trial in patients with advanced prostate cancer, the company believes Provenge may also have applicability to men with earlier stages of the disease. The company says that it is on track to complete the interim analysis of the ongoing Phase III IMPACT trial during the latter half of this year. Source: PRNewswire 7/16/08

Magnitude of Post-Vaccine Immune Response Linked to Clinical Outcomes

Researchers conducting a clinical trial of a dendritic cell vaccine designed to fight malignant brain tumors called glioblastoma multiforme have found a correlation between the "intensity" of a patient's immune response and clinical outcome, according to an article in the July 15 issue of the journal Cancer Research. While other studies have suggested a link, this is believed to be the first to show direct and continual proportionality between the strength of antitumor responses and clinical benefits in cancer patients. This also may be the first documentation of a definite immune response/patient outcome correlation that can be credited to tumor-altering therapeutic interventions. The study centered on the immune responses of 32 patients enrolled in a Phase II clinical trial. Seventeen patients had a significant positive response after three vaccinations; 15 showed no such responsiveness. Average time to tumor progression was about 308 days among responders, compared to 167 days for nonresponders. Average length of survival was about 642 days among responders, compared to 430 days for nonresponders. Forty-one percent of vaccine responders, compared to 7 percent of nonresponders, survived at least two years. All patients in the trial had longer time to progression and longer time of survival, on average, than patients undergoing standard treatment without vaccination, although their prevaccine disease courses were similar. The vaccine was first used experimentally in patient treatment in May 1998, and numerous studies have been conducted to fine-tune the therapy and combine it with other cancer-killing treatments. Certain rights in the dendritic cell vaccine technology and corresponding intellectual property have been exclusively licensed by Cedars-Sinai Medical Center to ImmunoCellular Therapeutics, Inc., including subsequently-developed versions of the vaccine investigated in this clinical study. Source: EurekAlert! 7/15/08

Three Pilot Studies Evaluate Continuous Glucose Monitoring System

Echo Therapeutics in July announced publication of results from three pilot clinical studies of its Symphony Transdermal Continuous Glucose Monitoring (tCGM) System in the Journal of Diabetes Science and Technology. The article highlights that each of the three pilot clinical studies produced positive results supporting the use of Echo's Symphony™ tCGM System for reliable, noninvasive, real-time continuous glucose monitoring, and its most recently developed skin permeation device, the Prelude™ SkinPrep System. Transdermal continuous glucose monitors were applied to patients with diabetes (Study I), patients undergoing cardiac surgery (Study II), and healthy volunteers (Study III). Reference blood glucose measurements were performed with glucometers or standard blood glucose analyzers. At the conclusion of the 24-hour studies, the data were postprocessed for comparison with the reference blood glucose values collected during the study periods. Data were validated for 10 subjects for 12 hours in Study I, and in eight subjects each for 24 hours in Study II and in Study III. Comparing predicted glucose versus reference blood glucose values, Study I yielded 89.6 percent in Zone A and 9.0 percent in Zone B in a Clarke error grid (222 data points), Study II yielded 86.4 percent in Zone A and 13.6 percent in Zone B (147 data points), and Study III yielded 89.9 percent in Zone A and 10.1 percent in Zone B (378 data points). Each of the three studies yielded positive results, with combined A and B percentages of 98.7 percent, 100 percent, and 100 percent in Study I, II, and III, respectively. Source: PRNewswire 7/14/08 

Therapy for Stage III Melanoma Demonstrates Impact on Relapse-Free Survival

Schering-Plough and the European Organization for the Research and Treatment of Cancer (EORTC) announced in July that long-term treatment with pegylated interferon alfa-2b in stage III melanoma patients had a significant and sustained impact on relapse-free survival (RFS), according to results of a randomized Phase III trial published in The Lancet. The study was the largest positive adjuvant trial ever conducted in patients with stage III melanoma. Among the most significant findings in the study, at 3.8 years median follow up, the risk of recurrence or death was reduced by 18 percent in the pegylated interferon alfa-2b arm compared to observation. The four-year RFS rate was 46 percent versus 39 percent in the observation arm. Peginterferon alfa-2b is not approved for treatment of melanoma in either the United States or the European Union, but is marketed as Pegintron™ for other indications. For the study, researchers randomized patients to either peginterferon alfa-2b adjuvant treatment (n=627) or observation only (n=629) within 70 days of regional lymph node dissection (intent-to-treat population). The endpoint was RFS. The study results presented were analyzed by the EORTC. Median RFS was 34.8 months and 25.6 months in the peginterferon alfa-2b and observation arms, respectively. The improvement in RFS was more pronounced in patients with a lower tumor burden in the lymph nodes based on predefined subgroups. Peginterferon alfa-2b adjuvant treatment was not associated with a benefit on overall survival, a secondary endpoint. Source: PRNewswire 7/11/08 

Prostate Cancer Vaccines More Effective with Hormone Therapy

Among patients with castration-resistant prostate cancer, the addition of hormone therapy following vaccine treatment improved overall survival compared with either treatment alone or when the vaccine followed hormone treatment, according to recent data published in Clinical Cancer Research. National Cancer Institute researchers enrolled 42 patients who had castration-resistant prostate cancer. These patients were randomly assigned to receive either a poxvirus-based prostate-specific antigen vaccine or hormone therapy with nilutamide. At progression, patients received the other therapy and continued to receive their original therapy. For all the patients enrolled in the study, the three-year survival probability was 71 percent and the median overall survival was 4.4 years. Patients randomized to the vaccine had a three-year survival probability of 81 percent and an overall survival of 5.1 years, while patients taking nilutamide had a three-year survival probability of 62 percent and an overall survival of 3.4 years. For patients who received vaccine and then nilutamide, the three-year survival probability was 100 percent with a median overall survival of 6.2 years. For patients who switched to the vaccine after hormone, the three-year survival probability was 75 percent with a median overall survival of 3.7 years. Building on the results of this Phase II study, researchers have developed another generation of this vaccine by adding molecules that boost T-cell responses, and are optimistic that overall prostate cancer research trends could lead to a new treatment vaccine within a few years. Source: EurekAlert! 7/10/08 

Japanese Phase III Trial Completed for Emergency Contraceptive Pill

Sosei Group Corp. in July announced the completion of a Japanese Phase III clinical trial for the emergency contraceptive pill (ECP) SOH-075 (NorLevo®). Sosei acquired the exclusive distribution rights to the product in Japan from HRA Pharma. The clinical study was designed to evaluate the safety and prevented pregnancy rate of SOH-075 in Japanese adult female subjects who require emergency contraception. No serious adverse events were reported during the study. Further announcement will be made when all study results are fully analyzed. NorLevo is an oral emergency contraceptive "morning after pill" that is used to prevent pregnancy after unprotected intercourse; it contains only levonorgestrel as an active ingredient. The dosing is started within 72 hours after unprotected sexual intercourse. NorLevo was first launched in Europe in 1999 and is currently approved in some 60 countries, the product being both well-tolerated and effective as an oral emergency contraceptive for postcoital use. The product would be the first ECP to be introduced into Japan. Earlier multinational studies performed by the World Health Organization demonstrated that levonorgestrel mono therapy was well-tolerated and more effective than the Yuzpe method (ethinyl estradiol and levonorgestrel), a traditional emergency contraception method used since 1977. Source: PRNewswire 7/10/08 

Phase III Data for Sustained Follicle Stimulant Meets Primary Endpoints

Schering-Plough Corp. announced in July that corifollitropin alfa, its experimental, sustained follicle stimulant met its primary endpoints in the Phase III ENGAGE trial, according to data presented during a symposium at the 24th annual meeting of the European Society of Human Reproduction and Embryology in Barcelona, Spain. The ongoing pregnancy rate, the primary endpoint of this noninferiority trial, obtained in the 150 mcg corifollitropin alfa treatment arm (38.9 percent per started cycle) was similar to that achieved in patients receiving 200 IU recombinant FSH (follitropin beta) (38.1 percent per started cycle). The number of oocytes retrieved (coprimary endpoint) was within the limits of clinical equivalence, and the estimated difference of +1.2 was in favor of the corifollitropin alfa 150 mcg treatment arm. Further results will be submitted for presentation at a future medical meeting. ENGAGE is the largest double-blind fertility trial ever performed. A total of 1,509 patients at 34 in vitro fertilization clinics in North America and Europe were randomized to receive either corifollitropin alfa 150 mcg or a daily dose of 200 IU recombinant FSH, followed by recombinant FSH (maximum 200 IU/day) from stimulation day 8 onward. Starting on stimulation day 5, all patients were scheduled to receive 0.25 mg gonadotropin-releasing hormone antagonist until triggering of final oocyte maturation by a urinary human chorionic gonadotropin. The primary endpoint was ongoing pregnancy rate assessed at 10 weeks or more after embryo transfer. The incidence of ovarian hyperstimulation syndrome was similar between both groups (7.0 percent in the corifollitropin alfa group [1.9 percent severe] and 6.3 percent in the follitropin beta group [1.3 percent severe]). Source: PRNewswire 7/8/08 

Biopure Announces Meeting With FDA

Biopure Corp. announced in July that it has had discussions with the Food and Drug Administration (FDA) on identifying an acceptable patient population for a new clinical trial of Hemopure® [hemoglobin glutamer-250 (bovine)], or HBOC-201. Biopure has proposed to study use of Hemopure in patients suffering from acute myelogenous leukemia (AML) who refuse transfusion with blood components. Currently, AML patients who do not accept blood transfusions are unable to undergo potentially life-saving induction chemotherapy because of the profound anemia the chemotherapy causes. Biopure is preparing to submit a protocol for such patients for consideration by FDA. Patients would give informed consent before being enrolled in this study. An effective treatment for this patient population represents an unmet medical need because of an expected 100 percent mortality within six months in the absence of induction chemotherapy. The purpose of the study would be to assess the efficacy of Hemopure in providing an oxygen carrier in lieu of transfusion with red blood cells, as an adjunct to other special procedures, following induction chemotherapy for AML. A successful trial in this population could be pivotal to establish an intended use for Hemopure in this clinical setting. Source: PRNewswire 7/7/08 

Positive Early Results Reported from Phase II Breast Cancer Study

Peregrine Pharmaceuticals, Inc. in July reported that its lead product candidate bavituximab achieved the prespecified Stage 1 primary endpoint in its ongoing Phase II clinical trial in patients with metastatic breast cancer. The trial is an open-label, Simon two-stage design to evaluate the safety and efficacy of a combination of bavituximab and docetaxel in metastatic breast cancer patients. Fourteen of the 15 patients enrolled in Stage 1 were deemed evaluable for tumor response, with seven achieving partial tumor responses and seven having stable disease at week eight according to RECIST criteria. All 14 of the evaluable patients remain in the study and are continuing to receive treatment, along with continuing assessments of tumor response. With the Stage 1 primary endpoint of six or more objective tumor responses achieved, the design of the clinical trial now allows for an additional 31 study patients to be enrolled. The primary objective of the multicenter trial is to assess overall tumor response rate. Secondary objectives include measuring time to tumor progression, duration of response, overall patient survival, and safety parameters. Patients may continue to receive bavituximab as solo therapy after completion of chemotherapy, as long as the cancer does not progress and side effects are acceptable. The trial is being conducted in the Republic of Georgia according to International Conference on Harmonization and Good Clinical Practices guidelines. Bavituximab currently is also in a Phase II combination therapy trials for the treatment of non-small cell lung cancer. A second Phase II combination therapy study in breast cancer patients is expected to begin soon. Source: PRNewsire 7/2/08 

Blood Vessel Inhibitor Shows Promise Against Metastatic Thyroid Cancer

Thyroid cancer that has spread to distant sites has a poor prognosis, but an experimental drug that inhibits tumor blood vessel formation can slow disease progression in some patients, a research team led by investigators from the University of Texas M. D. Anderson Cancer Center reported in the July 3 edition of the New England Journal of Medicine. The investigational drug, motesanib diphosphate, is a biologic agent that targets receptors on a protein known as vascular endothelial growth factor (VEGF). VEGF is instrumental in angiogenesis (formation of new blood vessels), a process that allows tumors to grow and spread. Researchers in 10 countries and scientists from Amgen, which is developing motesanib diphosphate (AMG 706), planned and conducted one of the largest clinical trials ever done for metastatic thyroid cancer. Of the 93 patients with rapidly progressing cancer who were enrolled in the study, 49 percent had a positive response. From that group, 14 percent had their tumors shrink and 35 percent had their tumors stabilize for more than 24 weeks. Median progression-free survival was estimated to be 40 weeks. Genetic analyses of 25 patients indicated that those with a specific mutation known as BRAF V600E in their tumors had a better response to motesanib diphosphate than did those without the mutation. Forty-two institutions internationally participated in the clinical trial, including an important collaboration with the Institut Gustave Roussy, M. D. Anderson's sister institution in Villejuif, France. The study enrolled patients with progressive, locally advanced or metastatic, radioiodine-resistant thyroid cancer. Thirty-two patients completed the full 48 weeks of treatment. Motesanib diphosphate was discontinued in 35 patients because of disease progression and in 12 patients because of drug-related adverse events. Five patients died, and nine withdrew for various administrative or personal reasons. The trial was funded by Amgen, Inc. Source: EurekAlert! 7/2/08 

Preliminary Response Rate Data Announced from Discontinued Colorectal Cancer Trial

ADVENTRX Pharmaceuticals, Inc. in July announced preliminary response rate results from its discontinued Phase III clinical trial of ANX-510, or CoFactor®, the company's folate-based biomodulator of 5-FU (5 fluorouracil), for the treatment of first-line metastatic colorectal cancer. The primary endpoint of the study was progression-free survival, which is expected to mature and be reported by the company along with safety data later this year. Data from the 85 patients treated in the study demonstrated a 39 percent objective response rate in the CoFactor/5-FU/Avastin® experimental arm compared to a 31.8 percent objective response rate in the leucovorin/5-FU/Avastin control arm. The data also demonstrated a 48.8 percent stable disease rate and 4.8 percent progressive disease rate in the CoFactor experimental arm compared to a 38.6 percent stable disease rate and 15.9 percent progressive disease rate in the leucovorin control arm. Objective response rate was measured according to RECIST criteria and was based on the number of complete responses and partial responses observed in this study based on investigators' assessments. Currently, there are 10 patients receiving treatment in this study, with six patients on the CoFactor experimental arm and four patients on the leucovorin control arm. Based on the data available at this time, the company intends to evaluate potential options for the continued development of CoFactor. As the company makes progress, it anticipates providing updates regarding its development plans for CoFactor. Source: PRNewswire 7/1/08 

Device Blocking Stomach Nerve Signals Shows Promise in Obesity

A new implantable medical device from EnteroMedics, Inc., developed in collaboration with Mayo Clinic researchers, shows promise as a reversible and less extreme alternative to existing bariatric surgeries, according to findings published in the current issue of the journal Surgery. In a six-month open label trial involving three medical centers in Australia, Mexico, and Norway, the 31 obese participants who received the vagal nerve blocking device, also called VBLOC™ vagal blocking therapy, lost an average of nearly 15 percent of their excess weight. A quarter of the participants lost more than 25 percent, and three patients lost more than 30 percent. The goal is to find a less drastic alternative to bariatric surgery that will still yield significant weight loss. In the study, researchers gained an initial assessment of whether blocking the vagus nerve electrically could cause obese patients to feel full after a normal-sized meal. Patients were not put on any restricted diets or given counseling that typically accompanies gastric banding or bypass. The patient flips a switch to activate the VBLOC device when the system is worn during the daytime hours, so that the blocking signal can influence how the stomach functions and food is digested following a meal. The lead wires are implanted in the abdomen laparoscopically, with electrodes attached to the vagal nerves and the neuroregulator, a pacemaker-sized device, is implanted just under the skin. The VBLOC delivery system can be removed if desired, and causes no distortion of digestive system anatomy. A follow-up double-blinded study, which will involve up to 300 patients at multiple medical centers, will be important for gauging the device's true effectiveness. Source: PRNewswire 6/26/08 

Company Launches Website Devoted to Myocardial Ischemia Trial

Cardium Therapeutics in June announced the launch of a new website to provide patients, caregivers, and physicians with information about the company’s Phase III AWARE clinical study. The AWARE study is evaluating the therapeutic effects of Generx™ for the potential treatment of myocardial ischemia (insufficient blood flow within the heart muscle) and associated angina due to coronary heart disease. Generx is designed to promote angiogenesis, a natural process of blood vessel growth within the heart muscle, following a one-time intracoronary infusion from a standard cardiac infusion catheter. The AWARE (Angiogenesis in Women with Angina pectoris who are not candidates for Revascularization) study, a randomized, placebo-controlled, double-blind trial, is planned to enroll approximately 300 women with recurrent stable angina pectoris who are not candidates for revascularization and who are receiving optimal drug therapy. The primary endpoint is the improvement in time to onset of electrocardiogram changes diagnostic of myocardial ischemia during exercise treadmill testing at six months following administration. The secondary endpoints are improvement in myocardial blood flow within the affected heart muscle measured by adenosine SPECT imaging, as well as improvements in other measures of angina. The AWARE study is expected to include up to 50 U.S. clinical centers. Source: Newswise 6/25/08

Phase II Study Initiated for Allergic Rhinitis Treatment

Morria Biopharmaceuticals Plc, in June announced that it has initiated a Phase II equivalent study of MRX-4, in a nasal aerosol formulation, in 105 patients suffering from allergic rhinitis (AR). The two-arm, randomized, multidose, double-blind, placebo-controlled study is expected to be completed by the end of the third quarter of 2008. It is designed to evaluate the safety, tolerability, and efficacy of intranasal MRX-4, a nonsteroidal product, in AR patients outside of the local allergy season as compared to both placebo and an intranasal steroid, Rhinocort®. In a Phase I equivalency trial completed in Israel earlier this year, MRX-4 was shown to be well tolerated with no clinical significant adverse effects. According to Morria's president, it is rare for a first-in-human efficacy study in AR to include a steroid comparator arm. Source: PRNewswire 6/24/08

First Breast Cancer Patient Enrolled in National Electronic Brachytherapy Registry

Xoft, Inc. in June announced the launch and of the EXIBT Study (Electronic Xoft Intersociety Brachytherapy Trial), a national electronic brachytherapy patient registry under oversight from three national physician societies—the American Brachytherapy Society, the American Society of Breast Surgeons, and the American College of Radiation Oncology. The first patient was successfully enrolled and treated in the registry by Drs. Peter Beitsch of the Dallas Breast Center and Timothy Nichols of the Northpoint Cancer Center in Dallas, Texas. With an enrollment goal of 400 patients, the objective of the multicenter study is to assess the long-term safety and efficacy of the Xoft Axxent® Electronic Brachytherapy System for the treatment of early-stage breast cancer patients. The primary endpoint is the measurement and quantification of skin and subcutaneous toxicities through five year follow-up. An important additional primary endpoint includes a quality of life questionnaire based on patient experience with this new form of radiation therapy. Secondary endpoints assess local/regional breast failure and patient survival through five years, as well as device performance. Source: PRNewswire 6/24/08

FDA Extends Review Period for Investigative Antiplatelet Drug

Daiichi Sankyo Co., Ltd. and Eli Lilly and Co. in June said that the U.S. Food and Drug Administration (FDA) has extended the review period for the prasugrel new drug application (NDA) based on supplemental information from the TRITON trial of more than 13,000 patients provided during the review period. This three-month extension allows the FDA time to complete its review. The prasugrel NDA was granted priority review by the FDA in February 2008. The new FDA action date for prasugrel is September 26, 2008. The proposed indication for prasugrel is for the treatment of patients with acute coronary syndromes (ACS) being managed with an artery-opening procedure known as percutaneous coronary intervention. The companies also confirmed the start in June, as planned, of the TRILOGY ACS trial, a Phase III clinical trial of approximately 10,000 patients at more than 800 hospitals in 35 countries to compare the effects of prasugrel against clopidogrel (Plavix®/Iscover®) in medically managed ACS patients. Daiichi Sankyo and Lilly are conducting the study in conjunction with the Duke Clinical Research Institute. Source: PRNewswire 6/23/08

Clinical Hold Lifted on Advanced Cancer Product

Genta Inc. announced in June that it has received notification from the FDA that the company may resume clinical trials with tesetaxel, an oral taxane being developed in Phase II studies for advanced cancer situations. The notification was made in response to the company's submission of a complete response to a prior notice from FDA that had placed the drug on "clinical hold" due to the occurrence of severe neutropenia that led to fatal outcomes in several patients. The company said that the FDA had determined that the company's initial submission addressed the agency's safety concerns by incorporating careful monitoring and supportive care to reduce risks. The company anticipates resuming clinical trials in the second half of this year. Tesetaxel could become the first oral taxane to receive regulatory approval. It is a novel, orally absorbed, semisynthetic taxane that is in the same class of drugs as paclitaxel and docetaxel. With administration as an oral capsule, tesetaxel was developed to maintain the high antitumor activity of the taxane drug class while eliminating infusion reactions, reducing neuropathy, and increasing patient convenience. The oral route also enables development of novel schedules that may expand dosing options when tesetaxel is used alone or in combination with other anticancer drugs. Source: PRNewswire 6/23/08

Antimucositis Agent Reaches Phase II in Cancer Patients

Canopus BioPharma, Inc. announced in June that the South African Medicines Control Council has granted approval for a Phase II study in 30 cancer patients evaluating the protective effect of CB1400 on the gastrointestional tract from radiation-induced mucositis. Oral and gastrointestinal mucositis is a painful, debilitating, and sometimes fatal side effect of radiation therapy and cancer chemotherapy. No preventative mucositis medicines are available, and few treatments are effective. With some cancer therapies, oral mucositis can develop in more than 90 percent of patients. In work carried out on behalf of Canopus, CB1400 has already been shown to have protective and antimutagenic effects when tested in an animal model of mucositis. The company has applied to undertake further clinical studies with oncologists in Australia, South Africa, and the United States to investigate CB1400 as a preventative mucositis agent in head and neck cancer patients who are receiving radiation and/or chemotherapy. Source: PRNewswire 6/23/08

New Oral Drug Reduces MS Disease Activity

According to results from a Phase II study that were reported in The Lancet in