Clinical Trial Updates

Phase III Data are Promising for Anti-RSV Antibody

MedImmune in May announced results from a Phase III study involving motavizumab, an investigational monoclonal antibody (MAb) that is being evaluated for its potential to prevent serious disease caused by respiratory syncytial virus (RSV) in high-risk pediatric patients. The randomized, double-blind study demonstrated that motavizumab reduced hospitalizations due to RSV by 83 percent as compared to placebo (8.3 percent in placebo arm versus 1.4 percent in motavizumab), as the trial’s primary endpoint. In addition, the trial showed a 71 percent reduction in the incidence of RSV-specific lower respiratory infections (LRIs) requiring outpatient management (9.5 percent in placebo group and 2.8 percent in the motavizumab group), which was a secondary endpoint. The study involved 1,410 full-term healthy infants less than six months of age in some Southwest Native American populations, and was designed to compare monthly intramuscular injections of motavizumab against placebo. In previous epidemiologic studies these populations were shown to have high rates of hospitalization due to RSV. This study confirmed the high rates of serious RSV disease in this population. An interim analysis, reviewed by an independent data safety monitoring committee, concluded there was statistical evidence demonstrating that motavizumab reduced RSV hospitalizations and LRIs requiring outpatient medical management within this population. Source: Newswise 5/5/08

Early Evidence Points to Superior Benefits of Drug Therapy for Diabetic Eye Disease

A Juvenile Diabetes Research Foundation collaboration between Johns Hopkins researchers and Genentech has shown that a drug for the treatment of diabetic eye disease has performed better in clinical trials than the current standard treatment using laser surgery. These findings, representing the six-month end-point evaluation of the READ-2 clinical trial coordinated by Johns Hopkins, were presented in April at the 2008 Annual Meeting of The Association for Research in Vision and Ophthalmology. The multicenter study began in December 2006, and was designed to test the long-term safety and effectiveness of injections of the drug ranibizumab in patients with diabetic macular edema, a condition characterized by swelling of the central portion of the retina, or macula, at the back of the eye. In addition, the trial sought to determine the comparative efficacy of ranibizumab versus conventional treatment (laser photocoagulation therapy) or both together. Participating in the clinical trial were 126 diabetic patients (average age 62); the majority had 20/80 vision in the eye that was treated. Patients treated with ranibizumab experienced significantly greater improvements in visual acuity, or clarity of vision, compared with patients receiving either of the other interventions. On average, the vision of ranibizumab-treated patients improved to 20/63 at month six, compared with essentially unchanged acuity scores of about 20/80 in both the laser and the combination treatment groups. In addition, patients treated with ranibizumab had a 56 percent reduction in excess retinal thickness, whereas only an 11 percent reduction was seen in those receiving laser treatments. Source: EurekAlert! 4/29/08

Drug Slows Decline of Mild Alzheimer's Patients in Phase II Study

Patients with mild Alzheimer's disease (AD) who take 800 mg of tarenflurbil (Flurizan™, Myriad Genetics) twice daily show less decline in functional ability than those taking placebo. The findings of this Phase II justify Phase III studies of tarenflurbil at this dose. These are the conclusions of the authors of an article published early Online and in the June issue of The Lancet Neurology. The randomized trial involved 210 AD patients whose score on a scale called the mini-mental state examination (MMSE) of 15-26 gave them a diagnosis of mild to moderate AD. The patients were randomly assigned to receive 400 mg tarenflurbil twice per day (69 patients); 800 mg tarenflurbil twice per day (70 patients); or placebo (71 patients). Effectiveness of the treatment was assessed using three common scores. Following the initial 12 months, there was a 12 month extension phase in which some patients who had received tarenflurbil continued on the same dose, and some on placebo were randomized to either the 400 mg or 800 mg doses. In the mild AD patients, the 800 mg tarenflurbil group experienced a rate of decline 46 percent lower than placebo patients in the activities of daily living scale; and tarenflurbil also reduced the pace of decline in global function by 36 percent. Patients with mild AD who were in the 800 mg tarenflurbil group for 24 months had lower rates of decline for all three primary outcomes than did patients who were in the placebo group for months 0-12 and either tarenflurbil group for months 12-24. Source: EurekAlert! 4/29/08

Cancer Immunotherapy Shows Long-Term Promise in Lung Cancer

New, long-term results from a Phase II clinical trial presented in April show that GlaxoSmithKline's MAGE-A3 ASCI (Antigen-Specific Cancer Immunotherapeutic), an immune-boosting treatment for lung cancer patients, reduces the risk of relapse after surgery to the same extent as chemotherapy, but without the side-effects of chemotherapy. The results come from 44 months of follow-up on a double-blind, placebo-controlled trial in 182 patients with nonsmall-cell lung cancer. After complete surgical resection of the tumor, patients were randomly assigned to receive either placebo injections or injections of MAGE-A3 ASCI administered over 27 months (five given at three-week intervals followed by eight given once every three months). MAGE-A3 is a tumor-specific antigen, expressed in 35 to 50 percent of nonsmall-cell lung cancer, but not on normal cells. After 44 months, 69 of 182 patients had experienced a recurrence of their cancer, including 57 deaths. Those given the MAGE-A3 injections had longer on average before their cancer recurred, were less likely to have any recurrence, and were less likely to die. A large Phase III trial of the therapy is now under way. Source: EurekAlert! 4/25/08

Analysis Shows Drug Combination Adds No Benefit in Lung Cancer

A clinical trial evaluating the benefit of adding the drug sorafenib to the combination of carboplatin/paclitaxel chemotherapy for lung cancer patients was stopped in February, based on results from an interim analysis, after an independent data monitoring committee concluded that the study would not meet its primary endpoint of improved overall survival. According to results presented in April, for some patients, the drug results in worse outcomes. Sorafenib is an oral multikinase inhibitor with anti-angiogenic and antiproliferative activity. The drug, marketed as Nexavar by Bayer, is already approved for use in more than 40 countries for liver cancer and more than 70 countries for renal cell cancer. The latest trial included 926 patients with unresectable stage IIIB/IV nonsmall-cell lung cancer who had received no prior systemic treatment. Patients were randomized to receive carboplatin plus paclitaxel, combined with either sorafenib 400 mg or placebo. After a formal review of the ongoing study, the trial's data monitoring committee recommended termination. Preliminary results showed a median overall survival of 10.7 months in the sorafenib group versus 10.6 months in the placebo arm. Sorafenib-treated patients with squamous-cell nonsmall-cell lung cancer had a greater mortality rate than those with nonsquamous histology. Researchers are still studying the drug in lung cancer, including an ongoing study examining adding it to the combination of cisplatin and gemcitabine. Source: EurekAlert! 4/25/08

Cisplatin Less Effective than Standard Treatment for Patients with Anal Cancer

When administered before chemoradiation, the common anticancer drug cisplatin neither improved disease-free survival nor reduced the number of colostomies needed when compared to the standard treatment for patients with anal canal cancer, according to a study published in the April 23 issue of the Journal of the American Medical Association. In the largest cooperative Phase III randomized controlled trial of its kind, a multicenter research team led by Jaffer Ajani, MD, professor in the Department of Gastrointestinal Medical Oncology at the University of Texas M. D. Anderson Cancer Center, compared the standard treatment regimen of fluorouracil plus mitomycin and radiotherapy to fluorouracil plus cisplatin and radiotherapy in 644 patients with anal canal cancer. The five-year disease-free survival rate was 60 percent in the mitomycin-based group and 54 percent in the cisplatin-based group. The five-year overall survival rate was 75 percent in patients receiving mitomycin versus 70 percent receiving cisplatin, with more cancer-related deaths in the cisplatin-based group (54 patients) compared to mitomycin-based group (28 patients). Patients who received cisplatin-based treatment resulted in significantly higher rates of colostomy (19 percent versus 10 percent). The study expanded on findings from two pilot studies that encouraged oncologists to believe that cisplatin could potentially be used to reduce the cancer in the primary tumor and lymph nodes prior to administration of concurrent chemoradiation. Source: Newswise 4/22/08

Company Discontinues Phase III Chronic Bronchitis Trial

Replidyne, Inc. announced in April that it has discontinued enrollment in a placebo-controlled Phase III clinical trial testing faropenem medoxomil (faropenem) in patients with acute exacerbation of chronic bronchitis (AECB). Replidyne took this action to conserve its cash assets and support initiatives that include pursuing strategic transactions and maintaining its research programs. The AECB study is one in a package of four clinical trials, including two in community-acquired pneumonia and one in acute bacterial sinusitis, recommended as a way forward by the U.S. Food and Drug Administration for a new drug application submission for faropenem to treat these three adult community respiratory tract infections. Replidyne has not initiated the other three trials, and consistent with prior guidance, further faropenem development will depend on Replidyne securing a partner for the program. Source: PRNewswire 4/23/08

Two New Therapies Show Promise for Cancer Patients

Clinical researchers at Scottsdale Healthcare and TGen in April announced the results of two clinical trials that show promise for patients battling cancer. The Phase I clinical trial findings, presented at the Annual Meeting of the American Association for Cancer Research, focused on basal cell carcinoma (BCC) and pancreatic cancer. In the first trial, a novel molecule, GDC-0449, shrank tumors in BCC while having limited side effects. The first patient treated in the trial has shown clinical improvement for approximately 450 days in the ongoing study. The trial, sponsored by Genentech, included clinical sites in Arizona, at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, Md., and at the Karmanos Cancer Institute in Detroit, Mich. In the second trial, a novel combination of two drugs (nanoparticle albumin-bound paclitaxel [Abraxane] and gemcitabine) showed a significant clinical benefit in more than 80 percent of pancreatic cancer patients. Researchers reported on the first 20 patients of what will eventually be a 42-patient trial. The trial, sponsored by Abraxis BioScience, also included clinical sites at South Texas Oncology and Hematology, P.A. in San Antonio, Texas, the University of Alabama at Birmingham, and at Johns Hopkins University. Source: EurekAlert! 4/15/08

Foundation Awards $5.6 Million for Phase II Clinical Trial on Inosine

The Michael J. Fox Foundation has announced a $5.6 million award to drive a Phase II clinical trial to investigate the potential of inosine—a naturally occurring chemical that gives rise to urate in the body—to slow or stop the progression of Parkinson’s disease (PD). The work is being funded under the Foundation’s LEAPS (Linked Efforts to Accelerate Parkinson’s Solutions) 2007 initiative. LEAPS 2007 was funded with a lead gift from the Edmond J. Safra Foundation. Urate is a natural metabolite and major antioxidant in humans. Previous studies found that healthy people with higher urate levels in the blood had a reduced risk of developing PD. More recent work, including a study published in April in the journal Archives of Neurology authored by two of the principal investigators on this LEAPS award, have linked higher urate levels to a possible slower progression of the disease. Ninety people recently diagnosed with PD will be enrolled in a randomized, double-blind clinical trial to determine whether and at what dose inosine can safely elevate levels of urate in cerebrospinal fluid. Three months after enrollment, cerebrospinal fluid will be tested for urate levels. If a tolerable dose of inosine adequately increases urate in the cerebrospinal fluid, subjects will continue on treatment for up to two years to assess long-term safety. Source: EurekAlert! 4/14/08

Company Terminates Negotiations with Potential Partners for Inhaled Insulin

Nektar Therapeutics announced in April that it has ceased all negotiations with potential partners for its inhaled insulin programs as a result of new data analysis from ongoing clinical trials conducted by Pfizer Inc. An increase in the number of new cases of lung cancer was observed in inhaled insulin patients as compared to the control group. All new incidences of lung cancer were in patients that are former smokers. "The concern over this new data analysis from ongoing clinical trials has resulted in the termination of all negotiations with potential partners," said Howard W. Robin, president and CEO of Nektar. "Fortunately, over the past year Nektar has significantly transformed its business, moving away from inhaled insulin. We have made great progress expanding our research efforts and have built a deep pipeline of novel partnered and proprietary drugs in various stages of development." Source: PRNewswire 4/9/08

Encouraging Preliminary Results Reported from Tuberculosis Vaccine Clinical Trial in South Africa

Dutch biotechnology company Crucell N.V., the Aeras Global Tuberculosis (TB) Vaccine Foundation, and the South African Tuberculosis Vaccine Initiative (SATVI) presented a progress update and immunology data from a Phase I Ad35 tuberculosis vaccine study at the biennial "Tuberculosis Vaccines for the World" conference in Atlanta, Ga., in April. The study, conducted in Worcester, South Africa, and launched in May 2007, is the second Phase I study in a current series of three and has revealed promising results. Preliminary data show both critical arms of the cellular immune system, CD4 and CD8 immune T-cells, were induced and that in those participants who responded, CD8 immune responses are considerably higher than has ever previously been seen in a TB vaccine study. The trial is being conducted as a double-blind, randomized, placebo-controlled, dose escalation study in four groups of healthy adults vaccinated at birth with BCG (Bacille Calmette-Guerin) vaccine. A total of 40 healthy adult volunteers are enrolled. A third Phase I study in healthy adults in St. Louis, Mo., was launched in December 2007 and focuses on the immunogenicity and safety of two AERAS-402/Crucell Ad35 boost doses administered at three to six month intervals after BCG priming in healthy adults. Source: PRNewswire 4/9/08

Phase I Clinical Results Announced for Novel Dry Mouth Treatment

Parion Sciences, Inc. in April announced preliminary results from a Phase I clinical safety study of a novel sodium channel blocker, P-552-02, as a topical therapy for dry mouth associated with primary Sjogren's syndrome. The preliminary results of the study showed that P-552-02 was safe and well tolerated, both locally in the oral cavity and systemically. No side effects or other safety issues were reported in the study. The results were reported by Athena Papas, DMD, PhD, a professor at Tufts University School of Dental Medicine at the Annual Meeting of the American Association for Dental Research. The trial was a 28-day, 30-patient, randomized, double-blind, placebo-controlled, crossover study designed to assess the effect of a six-time daily oral rinse formulation of P-552-02 versus placebo on oral and systemic safety parameters and the symptoms of dry mouth. The primary efficacy endpoint, a global improvement in the "feeling of dry mouth" as determined by a single retrospective "recall" report at day 28, was not met. However, an assessment of "global change in dry mouth" as determined by the change in visual analog scale measurements 12 hours after dosing at day 7 and day 28 revealed significant improvement in the global dry mouth scores. Scores that measured the change at day 28 in mouth dryness, tongue dryness, and ability to sleep also indicated that subjects improved on P-552-02 compared to placebo. The work was funded by Parion Sciences under a clinical study agreement with Tufts University. Source: PRNewswire 4/7/08

Renal Artery Stenting Falls Short in Large Randomized Trial

The largest-ever randomized study to evaluate the effectiveness of catheter-based interventions in patients with narrowing of the renal artery has shown that angioplasty and stenting offer no benefit over medical therapy. Among patients who completed one year of follow-up, there were no differences in the change in kidney function, blood pressure control, or the rates of major cardiovascular illness, according to the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial. The ASTRAL trial was reported in April at SCAI-ACCi2, a meeting of the Society for Cardiovascular Angiography and Interventions in partnership with the American College of Cardiology. The study also found that 3 percent of patients who underwent renal artery intervention experienced a serious procedural complication, including poorly positioned stents and perforation and dissection of the renal artery. To evaluate the clinical effectiveness of renal artery stenting, 806 patients with atherosclerotic renal vascular disease were recruited from 54 medical centers in the United Kingdom, and four in Australia and New Zealand. The researchers randomly assigned patients to catheter-based intervention plus medical therapy or medical therapy alone. Renal artery stenting was successful in widening the renal artery, achieving a residual stenosis of less than 50 percent in 88 percent of patients. After one year of follow-up, however, there were no differences in the change in serum creatinine—it rose by 0.2 mg/dL in both groups—or in rates of renal events, including acute renal failure. Source: EurekAlert! 4/1/08

Vascular Plug Gets Good Reviews in Study

ExoSeal, a new bioabsorbable plug that seals the arterial puncture site used for threading catheters into the body during diagnostic angiography and interventional procedures, significantly shortens bleeding time and enables patients to get up and walk around far sooner than when manual compression is applied to the groin. In addition, there were no access site complications at 30 days in the ECLIPSE Trial, a multicenter randomized study that is testing the safety and effectiveness of the investigational ExoSeal vascular closure device. The study was reported in April at SCAI-ACCi2. The device consists of a felt-like plug made of polyglycolic acid. It is anchored in place on top of the puncture in the femoral artery, after the catheter is removed. Because none of the plug is inserted into the artery itself, it does not interfere with blood flow. Over about three months, it completely dissolves. By comparison, manual compression involves exerting pressure on the femoral artery by hand or through use of a weight or clamp. This process can be uncomfortable for patients. It can take up to roughly 20 minutes for the bleeding to stop and several hours before the patient can get up from lying flat in bed. For the study, 488 patients were recruited from 17 medical centers and randomly assigned to treatment with the ExoSeal or to manual compression. The device was put into place in an average of just one minute and was used successfully in 89.1 percent of patients. There was no difference in procedural success between the ExoSeal and manual compression groups (91.8 percent and 91.0 percent, respectively). However, the average time to cessation of bleeding was significantly shorter in patients treated with the ExoSeal (4.38 minutes versus 20.05 minutes). Similarly, patients treated with the vascular closure device were able to get out of bed and walk around far sooner, on average within 2.54 hours with the ExoSeal, as compared to 6.24 hours with manual compression. Source: EurekAlert! 4/1/08

Final Data Suggest Safety, Efficacy of Autologous Stem-Cell Therapy for Congestive Heart Failure

Final six-month, follow-up patient data presented in April at sessions at the American College of Cardiology suggest MyoCell® myoblast clinical cell therapy is a safe and potentially effective alternative treatment to standard medical therapy alone for improving heart function among patients with previously implanted cardiac devices who are experiencing congestive heart failure. The findings from the SEISMIC Trial, a 40-patient, randomized, multicenter, controlled, Phase IIa study conducted in Europe, evaluated the therapy delivered via the MyoCath®, an endoventricular needle-injection catheter, in patients previously fitted with implanted cardiac defibrillators(ICDs) who are receiving standard medical therapy and are experiencing congestive heart failure. On admission to the trial, patients were randomized on a two-to-one ratio into the treatment versus control groups with 26 patients receiving MyoCell therapy and 14 patients in the control group. The results showed that 84 percent of treated patients experienced improved or unchanged six-minute walking test scores compared to 16 percent of the control group (69 percent of the control group's results worsened versus only 16 percent of the treated group); and 94 percent of treated patients experienced improved or unchanged NYHA classification compared to 58 percent of the control group (42 percent of the control group's results worsened versus only 6 percent of the treated group). Reports of arrhythmia among the patients evaluated in SEISMIC, both in terms of total number of episodes as well as timing of episodes, were no different between the treatment and control arms in the study. A larger, more comprehensive MARVEL Trial is currently under way in the U.S. and Europe as a randomized, double-blind, placebo-controlled, multicenter Phase II/III study of 330 patients. Source: PRNewswire 4/1/08

Phase III Trial Disontinued for Patients with Advanced Melanoma

Pfizer Inc announced in April that it had discontinued a Phase III clinical trial (A3671009) of single-agent tremelimumab (CP-675,206) in patients with advanced melanoma after the review of interim data showed that the trial would not demonstrate superiority to standard chemotherapy. Pfizer has communicated with worldwide regulatory authorities and investigators regarding the discontinuation of the trial. Investigators will work with their patients to determine if they are benefiting from treatment and therefore should continue treatment with tremelimumab. All patients are encouraged to contact their physician with questions about their treatment. “Although this outcome is disappointing, Pfizer remains committed to investigating new treatment options for patients with melanoma, a high risk area of research with significant unmet medical need. We continue to focus on additional studies involving tremelimumab alone and in combination with other therapies which are currently ongoing in patients with several types of cancer,” said Charles Baum, MD, PhD, vice president and oncology therapeutic area head at Pfizer Global Research and Development. “We will continue to assess the study data to understand the clinical benefit seen in some patients who received tremelimumab.” The full data set from the study is being analyzed, and more details are expected to be available at the American Society for Clinical Oncology Annual Meeting in June 2008. “We are extremely grateful for the strong support we have received for this clinical trial from the physicians, study staff, and most importantly from the patients,” Baum said. Source: Pfizer 4/1/08

Phase III Studies on Multiple Lipid Problems Meet Primary Endpoints

New data from two Phase III studies show that in patients with multiple lipid problems, Abbott's ABT-335 combined with two commonly prescribed statins (atorvastatin and simvastatin) significantly improved three key lipids (LDL "bad" cholesterol, triglycerides, and HDL "good" cholesterol) compared to the corresponding monotherapies. Results were presented in March at the American College of Cardiology 57th Annual Scientific Sessions in Chicago. ABT-335, an investigational new fenofibric acid molecule, will be known as TriLipix™. Both TriLipix studies are part of the largest clinical program to date designed to evaluate the efficacy and safety of a fibrate in combination with statins. These studies using fenofibric acid combined with atorvastatin and simvastatin met their primary endpoints. Combination therapy significantly improved HDL and triglycerides compared to statin therapy alone, and significantly improved LDL compared to TriLipix alone. Both the combinations and the two statins had clinically meaningful reductions in LDL. In the clinical trials, combination therapy was generally well tolerated, with reported safety similar to the monotherapies. No rhabdomyolysis or unexpected liver, kidney, or muscle safety signals were identified. So far, the efficacy and safety of TriLipix in combination with the three most commonly prescribed statins (rosuvastatin, atorvastatin, and simvastatin) have been evaluated in three randomized, multicenter, double-blind, controlled, 12-week Phase III studies, totaling 2,698 patients with mixed dyslipidemia. Patients included in the studies had multiple lipid problems, with an LDL greater than 130 mg/dL, triglycerides greater than 150 mg/dL, and HDL less than 40 mg/dL for men and less than 50 mg/dL for women. These studies, along with a 52-week, long-term efficacy and safety open-label extension study of 1,911 patients, represent the largest program to date examining the efficacy and safety of a fibrate in combination with statins. More than 2,200 patients were treated with TriLipix in combination with statins across the four studies. Source: PRNewswire 3/31/08

New Data Show Prevention of Progression of Atherosclerotic Plaque Volume

New data from a clinical trial using intravascular ultrasound (IVUS) technology found that in patients living with Type 2 diabetes, Takeda Global Research & Development's Actos® (pioglitazone HCl) reduced the atherosclerotic burden in the coronary arteries compared to glimepiride, and prevented progression compared to baseline. These 18-month data from the PERISCOPE trial were presented in March at the 57th Annual Scientific Session of the American College of Cardiology in Chicago. According to the company, studies conducted over the past 10 years in more than 16,000 patients, including short- and long-term trials, as well as prospective and observational studies, have shown no evidence that Actos is associated with an increased risk of heart attack, stroke, or death. A company spokesperson notes that, while not definitive, data from PERISCOPE combined with results from a previous study, looking at surrogate endpoints, have shown a consistent trend toward decreasing cardiovascular risk by reducing the atherosclerotic burden in people with Type 2 diabetes. PERISCOPE is the first clinical trial to examine the effects of an oral antidiabetic medication on the development of coronary atherosclerosis in patients with Type 2 diabetes using IVUS technology. The trial was conducted with 543 patients in 97 centers in the U.S., Canada, and Latin America. The number of episodes of a common cardiovascular endpoint of cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke, was six (2.2 percent) in glimepiride patients and five (1.9 percent) in Actos-treated patients. The number of hospitalizations due to congestive heart failure was equivalent in both arms. The data are consistent with the findings of the CHICAGO trial, an 18-month, multicenter, randomized study that enrolled 462 patients with Type 2 diabetes. Source: EurekAlert! 3/31/08

Investigational Antirestenosis Drug Disappoints

A new medication that researchers had hoped would reduce the risk of arterial renarrowing after stenting has turned in a disappointing performance in a multicenter clinical trial, but the multireservoir stent that was used to deliver the drug is still considered promising. Pimecrolimus, an anti-inflammatory medication already used in Novartis' Elidel® Cream for ecezma, was expected to reduce arterial inflammation and, therefore, the overgrowth of scar tissue, or neointimal hyperplasia, that causes in-stent restenosis. Instead, patients treated with pimecrolimus-eluting stents in a 248-patient study at 18 centers in Europe and Israel fared far worse than patients treated with stents that delivered a combination of pimecrolimus and paclitaxel, or paclitaxel alone, according to the randomized GENESIS study. Paclitaxel is also an antirestenosis medication, but it works by inhibiting cell division, rather than by reducing arterial inflammation. The study was terminated early by its sponsors. The data gathered to that point were reported in March at the Society for Cardiovascular Angiography and Interventions Annual Scientific Sessions in partnership with the American College of Cardiology. The GENESIS study was also designed to test a novel stent featuring reservoirs that are filled individually with an active drug and resorbable polymer matrix. This design enables the stent to deliver more than one drug at a time from adjacent reservoirs. In the case of the GENESIS study, the Conor Medsystems SymBio™ stent was loaded with two medications that inhibit restenosis by two different pathways. Despite the disappointing performance of pimecrolimus, the new reservoir stent design continues to undergo clinical testing with other medications. Source: EurekAlert! 3/31/08

New Drug Treatment Could Improve Outcomes for Patients with Coronary Stents

Prasugrel, a new antiplatelet agent under development by Eli Lilly and Co. to provide higher levels of platelet inhibition than current standard therapies, could provide more consistent protection from ischemic events than standard treatment in patients who have had at least one coronary stent, according to an article published in The Lancet. The results were presented at the American College of Cardiology Meeting in March. Narrowing or blockages in the arteries that supply blood to the heart can result in acute coronary syndromes, such as heart attack, stroke, and unstable angina. Interventions such as balloon angioplasty and stents are used to treat the narrowing of these arteries. Although stent use has resulted in greater procedural success and lower rates of renarrowing of the arteries than has balloon angioplasty alone, the use of coronary stents can result in blood clots that can block the stented artery, a condition known as stent thrombosis. Patients therefore need to take antiplatelet medications or anticoagulants after stent insertion to prevent blood clots from forming. Standard treatment is to use clopidogrel, one of a group of compounds known as thienopyridines, which prevent platelet aggregation, together with aspirin. The TRITON-TIMI 38 study assessed the effect of prasugrel, a new thienopyridine, compared with clopidogrel in patients with moderate to high-risk acute coronary syndromes who were undergoing percutaneous coronary intervention. Researchers did a subanalysis of the TRITON-TIMI 38 data to assess the rate, outcomes, and prevention of ischemic events in 12,844 patients with different types of intracoronary stents who were treated with prasugrel plus aspirin or clopidogrel plus aspirin. The investigators found that intensive antiplatelet therapy with prasugrel resulted in fewer ischemic outcomes, including stent thrombosis, than with standard clopidogrel, irrespective of the type of stent used. Source: EurekAlert! 3/29/08

Company Announces Termination of Phase IV Trial for Diabetes Treatment

Keryx Biopharmaceuticals, Inc. announced in March that, following a drug safety and monitoring committee (DSMC) review of the SUN-MACRO Phase IV trial of Sulonex™ (sulodexide oral gelcap) for the treatment of diabetes, the company has decided to terminate the study and cease further development of the product. The company previously announced via conference call on March 10 that the trial had been suspended pending an interim analysis, following which the company would make a decision regarding whether the trial ought to be continued or terminated. Based on a review of the available proteinuria data, Sulonex did not appear to be different from placebo. The study was not terminated by the DSMC for any safety problem or safety signal. Source: PRNewswire 3/27/08

Positive Early Results for Phase II Trial of Oral Compound for Cystic Fibrosis

The Cystic Fibrosis Foundation announced in March that VX-770, an investigational oral drug that targets a basic defect in cystic fibrosis (CF), showed promising results in an ongoing Phase IIa clinical trial for patients who carry the G551D mutation of CF. The drug is being developed by Vertex Pharmaceuticals Inc. Patients who took the drug for 14 days showed significant improvements in several key indicators of CF, including lung function, nasal potential difference measurements, and sweat chloride levels. The findings suggest that VX-770 improves function of what is known as the faulty CFTR protein. This is the first time that any potential therapy has improved the abnormal sweat chloride (salt) levels in a person with CF. Excessive sweat chloride is a key clinical indicator of CF, and the "sweat test" is the traditional diagnostic test for CF. "These early results are an extraordinary endorsement of our hypothesis—that small molecules can correct the basic defect and affect the clinical indicators of cystic fibrosis," said Robert J. Beall, PhD, president and CEO of the foundation. "The emerging data for VX-770 represent the most exciting results we've seen from a Phase II trial, and increase our confidence that we're on the right track." The compound VX-770 resulted from a collaboration between the foundation and Vertex. Part one of the trial involved 20 CF patients; part two is expected to begin in the second quarter of 2008. Additional studies will evaluate the longer term safety and efficacy of the compound. Source: PRNewswire 3/27/08

Phase III Trial Initiated for Pancreatic MRI Imaging Aid

Repligen Corp. in March announced that it had initiated a Phase III clinical trial to evaluate the use of RG1068, a synthetic version of human secretin, a natural gastrointestinal hormone involved in digestion, to improve the assessment of pancreatic duct structures by magnetic resonance imaging (MRI). The multicenter, baseline-controlled, single-dose study will involve approximately 250 patients receiving an unenhanced MRI followed by a secretin-enhanced MRI of the pancreas. The study is designed to assess the sensitivity and specificity of secretin-enhanced MRI to improve the ability to detect pancreatic duct abnormalities relative to MRI alone. Detailed visual assessment of the pancreatic ducts is important in the assessment, diagnosis, and treatment of diseases such as acute and chronic pancreatitis. This study is being conducted at approximately 30 clinical sites within the United States and Canada. Repligen previously conducted a multicenter, baseline-controlled, single-dose Phase II study, in which 76 patients with a history of pancreatitis received an unenhanced pancreatic MRI followed by a RG1068-enhanced pancreatic MRI. The results of the study showed an improvement in sensitivity of detection of structural abnormalities of the pancreatic duct of approximately 20 percent with no loss in specificity. In addition, the study showed highly significant increases in physician confidence in their ability to identify structural abnormalities, the number of pancreatic duct segments visualized, and improvement in the overall quality of the MRI images. Source: PRNewswire 3/26/08

Five-Year Data Show Low Incidence of Resistance to Hepatitis B Treatment

New Baraclude® (entecavir) data presented in March demonstrated a continued low incidence of resistance in nucleoside-naïve patients through five years of treatment. In the nucleoside-naïve chronic hepatitis B patients analyzed, no additional patient developed resistance in the fifth year. Through five years of treatment, the cumulative probability of developing mutations in the virus that confer resistance to the drug (also called genotypic resistance) was 1.2 percent. Bristol-Myers Squibb Co. announced the results at the 18th Conference of the Asia-Pacific Association for the Study of the Liver in Seoul, Korea. In lamivudine-refractory patients who received Baraclude after treatment with lamivudine failed, the cumulative probability of genotypic Baraclude resistance was 51 percent through the fifth year. This finding is consistent with prior observations that the pre-existence of lamivudine-resistant mutations results in an increase in the rate of Baraclude resistance. Drug resistance occurs when the hepatitis B virus mutates, thereby avoiding the effects of the medication. This can decrease the efficacy of the current medication and may compromise future treatment options. To date, studies have shown that multiple mutations are required to develop Baraclude resistance. More than 700 patients across six studies initiated therapy on Baraclude and were monitored for treatment response and resistance. The year five analysis included information on 108 patients in nucleoside-naïve studies and 33 patients in lamivudine-refractory studies. Source: EurekAlert! 3/24/08

Enrollment Completed in Phase III Study of Blood Substitute

Sangart, Inc. in March announced that it had completed enrollment in a Phase III trial of its lead blood substitute product, Hemospan®. The study of 460 patients is one of two parallel Phase III clinical trials being conducted at 36 academic medical centers in the United Kingdom, Sweden, the Netherlands, Belgium, Poland, and the Czech Republic. The two randomized, placebo-controlled studies, which will enroll a combined total of more than 800 elective orthopedic surgery patients, are designed to evaluate the safety and efficacy of Hemospan in preventing and treating hemodynamic instability, especially hypotension, or low blood pressure, during surgery. Sangart also announced that enrollment in the second Phase III study is progressing well, and is expected to be completed in the near future. Hemospan was designed using polyethylene glycol conjugation to create a hemoglobin-based product that is intended to serve as an alternative to donated blood. According to the company, no similar oxygen transport agents are currently on the market in Europe or the United States. Earlier clinical studies indicate that Hemospan's novel oxygen delivery mechanism has the potential to provide a safe and effective alternative to blood transfusions. Source: PRNewswire 3/24/08

Positive Results Announced from Clinical Trial of Ovarian Tumor Triage Test

Vermillion, Inc. in March announced preliminary results from a clinical trial evaluating its Ovarian Tumor Triage Test. The study met its primary endpoints, demonstrating that the test successfully stratifies women with pelvic masses into high- and low-risk categories to determine whether the patient should be referred to a specialist prior to surgery. The results indicate that use of the test could significantly increase the percentage of high-risk cases referred to the appropriate specialist for treatment, ultimately improving survival rates. The ovarian biomarker panel ruled out malignancy with approximately 95 percent certainty or negative predictive value. Negative predictive value is the probability that the patient is free of disease based on diagnostic evaluation. The panel also showed approximately 90 percent sensitivity for detecting malignant ovarian tumors. The prospective clinical trial was one of the largest ever conducted and assessed more than 550 patients with a confirmed adnexal mass at 27 clinical trial sites in the United States. Vermilion plans to submit this in vitro diagnostic test to the U.S. Food and Drug Administration for clearance. Studies show that women with ovarian cancer who are initially operated on by a gynecologic oncologist have improved median and overall survival and have a better chance of being cured. Vermillion's ovarian tumor triage test utilizes a panel of biomarkers to help identify women at high risk of having cancer so that they can be referred directly to a gynecologic oncologist for their initial surgery. Source: PRNewswire 3/20/08

Arthritis Drug is Effective in Trials in Both Adults and Children

According to an article in a recent issue of The Lancet, the anti-arthritis drug tocilizumab (Roche and Chugai's Actemra) has proven effective in two separate trials, one involving rheumatoid arthritis (RA) in adults and the other involving systemic-onset juvenile idiopathic arthritis (SOJIA) in children. In both conditions, the cytokine compound interleukin 6 is involved in activation of the cells of the immune system, helping cause inflammation. The authors of both studies aimed to assess the effects on blocking the interleukin 6 receptor using tocilizumab. In the first article, researchers at the Medical University of Vienna, Austria, conducted the OPTION study, a Phase III trial of 623 adults with moderate to severe RA. At 24 weeks, 59 percent of patients in an 8 mg/kg group, 48 percent in an 4 mg/kg group, and 26 percent in a placebo group had recorded desirable responses. In the second article, researchers at the Yokohama City University School of Medicine, Japan, conducted a Phase III study of 56 children and young adults with SOJIA whose symptoms had not improved with conventional arthritis treatments. Following a lead-in stage, 43 of the patients progressed to the randomization stage. The researchers found that 16 out of 20 patients receiving tocilizumab maintained the desired responses to treatment compared to just four out of 23 in the placebo group. Source: EurekAlert! 3/20/08

Heart Institute Now Enrolling Women with Recurrent Chest Pains for Clinical Trial

The Cedars-Sinai Heart Institute is recruiting female patients with recurrent chest pains who are not eligible for surgery to participate in a clinical trial studying an experimental product designed to promote blood vessel growth within the heart muscle. The AWARE trial will study the effects of Cardium Therapeutics' Generx™ (alferminogene tadenovec, Ad5FGF-4) in women for the potential treatment of myocardial ischemia (insufficient blood flow within the heart muscle), which can cause chest pains (angina) associated with coronary heart disease. Generx is an investigational product designed to promote angiogenesis, a natural process of blood vessel growth within the heart muscle. The randomized, placebo-controlled, double-blind study will enroll approximately 300 women with recurrent stable angina pectoris who are not candidates for revascularization and who are receiving optimal drug therapy. The primary effect of the investigational medication will be measured during an exercise treadmill test done at baseline and again at six months. The secondary effect will be measured through the myocardial blood flow using single photon emission computed tomography and other tests for angina. Cedars-Sinai is among an estimated 50 centers nationwide participating in the AWARE trial. Source: Newswise 3/18/08

Diabetes Vaccine Receives Approval to Start Phase III Trials in Europe

Diamyd Medical announced in March that the Swedish Medical Products Agency has approved the company's application to commence Phase III studies with the therapeutic diabetes vaccine Diamyd®. Professor Johnny Ludvigsson, Linkoping, Sweden, will serve as principal investigator for the study. Diabetes teams from approximately 20 Swedish pediatric clinics will meet in Linkoping on April 4 to go through details for the study, which will comprise 306 new onset Type 1 diabetes patients. Diamyd Medical is planning to file clinical trial applications in another three or four European countries, and to include an additional 20 clinics in the study. The company has also received authorization from the U.S. Food and Drug Administration to start a parallel Phase III trial in the United States. Source: PRNewswire 3/19/08

Phase III Trial Finds Survival Increase in Advanced Non-Small Cell Lung Cancer

BioNumerik Pharmaceuticals, Inc. and ASKA Pharmaceutical Co., Ltd. in March announced the results of a Phase III clinical trial of Tavocept™ in patients with advanced non-small cell lung cancer. The multicenter, double-blind, randomized, placebo-controlled trial included 182 patients who received the chemotherapy drugs paclitaxel and cisplatin as first-line therapy every three weeks. Half of all patients in the trial received Tavocept along with their chemotherapy, while the other half received a placebo and chemotherapy. The trial results indicate that the number of patients reporting either severe sporadic or cumulative neuropathy was approximately 50 percent lower in the Tavocept arm of the trial compared to the placebo arm. Although this outcome represents a strong trend in favor of Tavocept, the results are not statistically significant. BioNumerik and ASKA believe the lack of statistical significance is likely due to the relatively small size of the trial. The results also indicate that the median survival time for patients receiving Tavocept was approximately 40 days longer than for patients receiving placebo. For patients with adenocarcinoma, the most frequently occurring type of lung cancer, the median survival time was increased by approximately 138 days for patients receiving Tavocept compared to those receiving placebo. Source: PRNewswire 3/18/08

Catheter Opener Development Discontinued After Disappointing Phase II Trial

Nuvelo, Inc. in March announced that data from its Phase II program in catheter occlusion (CO), known as SONOMA-3, did not show sufficient improvement in catheter opening at the higher dose and concentration evaluated in the study to meet the desired target product profile. As a result, Nuvelo has ended further clinical development of alfimeprase, including its programs in CO and acute ischemic stroke. In the open-label, single-arm trial, alfimeprase restored catheter function in approximately 50 percent of patients at 15 minutes and approximately 60 percent of patients at one hour. While the 15-minute clearance rate represents an improvement over the previous SONOMA-2 trial, which evaluated a lower dose and concentration of alfimeprase than SONOMA-3, the clearance rate at one hour fell short of the company's expectations. Cathflo®Activase®, the product currently on the market for catheter occlusion, has been shown to restore catheter function in more than 80 percent of occluded catheters within two to four hours. Source: PRNewswire 3/17/08

Top-Level Findings Reported from Phase IIb Study in Herpes Labialis

NanoBio Corp. reported top-level findings in March from its Phase IIb study of NB-001, a topical lotion to treat herpes labialis (cold sores). The randomized, double-blind, vehicle-controlled study met its primary and secondary endpoints by demonstrating efficacy and safety in 482 patients at magnitudes comparable to or superior to what has been reported for the leading oral (systemic) antiherpetic drugs on the market. Based on the data, NanoBio is planning a Phase III test of NB-001 in early 2009. The full data set from the Phase IIb study will be presented following a standard peer review process. NB-001 is a proprietary oil-in-water emulsion composed of nanometer-sized droplets that employ a physical process to disrupt the outer lipid membrane of viruses. The droplets traverse the pores and hair follicles of the skin without disrupting normal tissues. These droplets accumulate in the epidermis and dermis, where they interact directly with and kill the viral organisms at the site of infection. According to the company, the product's mechanism leaves little risk of drug resistance, which is a concern with the systemic antiviral therapies used to treat herpes labialis. Source: PRNewswire 3/17/08

FDA Says Leukemia Treatment Will Require Additional Confirmatory Data

Genta Incorporated announced in March that the U.S. Food and Drug Administration's (FDA) Center for Drug Evaluation and Research (CDER) has decided that available data are not adequate to support approval of Genasense® (oblimersen sodium) for treatment of patients with relapsed or refractory chronic lymphocytic leukemia (CLL). CDER recommended two alternatives for exploring the efficacy of Genasense that could provide such confirmatory evidence. One option is to conduct an additional clinical trial. The other option is to collect additional information regarding the clinical course and progression of disease in patients from the previous pivotal trial, in order to ascertain whether those data contain sufficient confirmatory evidence. The company currently plans to pursue both of these options. In parallel with collection and analysis of existing data in CLL, Genta has developed a new clinical trial, and the company will file its draft protocol at the May meeting of the European Medicines Agency. The proposed protocol, based on results obtained during the previous 241-patient Phase III trial, is a randomized controlled trial at first or second relapse in patients who are nonrefractory. Source: PRNewswire 3/17/08

First Clinical Trial Data Published on Fully Bioabsorbable Drug-Eluting Stent

Data published in March in The Lancet from ABSORB, the world’s first clinical trial of a fully bioabsorbable drug-eluting stent for the treatment of coronary artery disease, demonstrated no stent thrombosis, no clinically driven target lesion revascularizations (retreatment of a diseased lesion), and a low rate of major adverse cardiac events (MACE) in 30 patients out to one year. Abbott's prospective, nonrandomized ABSORB clinical trial is designed to evaluate the stent's overall safety and performance out to five years. At six months, the overall MACE rate in the ABSORB trial was 3.3 percent (one patient) and late loss, a measure of reduction in vessel lumen diameter after stenting, was 0.44 mm. At one year, the overall MACE rate in the ABSORB trial was consistent with results at six months. Unlike a metallic stent, a bioabsorbable stent is designed to be slowly metabolized by the body and completely absorbed over time. The ABSORB trial is a prospective, nonrandomized (open-label) study designed to enroll up to 60 patients in Belgium, Denmark, France, New Zealand, Poland, and The Netherlands. Source: EurekAlert! 3/13/08

Phase III Results Promising for Topical Treatment of Diabetic Foot Infection

MacroChem Corp. in March presented results of two Phase III clinical studies, individually and combined, comparing the efficacy of an investigational topical antimicrobial peptide preparation (pexiganan acetate cream) to systemic therapy with an oral fluoroquinolone antibiotic (ofloxacin) for mildly infected diabetic foot ulcers. The results, summarized in a poster at the Diabetic Foot Global Conference 2008 in Los Angeles, show that the rates of clinical cure or improvement for topical pexiganan and oral ofloxacin were statistically equivalent for the combined studies. The trial's principal investigator said that the combined studies may be the largest on treatment of diabetic foot infections ever conducted. The company has initiated manufacturing and formulation programs to scale-up for an anticipated undertaking of one more Phase III trial, the design of which is to be confirmed upon meeting with the FDA later this year. There are currently no other topical anti-infectives that have been proven effective in treating diabetic foot infections. Source: PRNewswire 3/13/08

Enrollment Completed in Pivotal Phase III Studies of Investigational Cancer Drug

AstraZeneca announced in March that it has completed patient enrollment in two pivotal Phase III studies for vandetanib, the company’s investigational, once-daily oral anticancer drug, for the second-line treatment of non-small cell lung cancer (NSCLC). The two studies, known as ZODIAC and ZEAL, are the second and third of four ongoing studies to complete enrollment. Data from the studies are expected later this year and the broad development program is on track for a first regulatory submission in 2008. ZODIAC is a randomized, double-blind, international, multicenter study to assess the efficacy of vandetanib 100 mg once daily plus the standard docetaxel chemotherapy versus docetaxel alone in 1,380 patients with locally advanced or metastatic NSCLC after failure of first-line anticancer therapy. ZEAL is a parallel group, randomized, double-blind study evaluating vandetanib 100 mg once daily plus pemetrexed 500 mg/m2 (every three weeks) compared to placebo plus pemetrexed as second-line treatment in 510 patients with locally advanced or metastatic NSCLC who have failed first-line anticancer therapy. Source: EurekAlert! 3/12/08

FDA Agrees to Amend Special Protocol Assessment for Phase III Study of Prostate Cancer Treatment

Dendreon Corp. in March announced that the FDA has agreed to an amended Special Protocol Assessment for the Phase III IMPACT clinical trial of Provenge® (sipuleucel-T), the company's investigational active cellular immunotherapy for the treatment of advanced prostate cancer. In addition, the FDA has reconfirmed that it would accept a positive interim or final analysis from the IMPACT trial to amend the Biologics License Application for licensure of Provenge. The amendment accelerates the expected timing of the final IMPACT results by approximately one year. By increasing the number of events and decreasing the alpha (false positive error) spending function for the interim analysis, the company is able to reduce the number of events for the final analysis (from 360 to 304) and still maintain a comparable statistical power for both the interim and final analyses. Interim results are still expected in the second half of 2008; however, final results are now expected in the second half of 2009 rather than 2010. Source: PRNewswire 3/12/08

Huntington's Disease Treatment to Proceed to NIH-Sponsored Phase III Trial

Avicena Group, Inc. announced in March that it met with the FDA and will proceed with a Phase III trial of its lead drug candidate, HD-02, for the treatment of Huntington's disease, pending final analysis of completed animal toxicology studies. A double-blind, placebo-controlled trial led by researchers at Massachusetts General Hospital, the University of Rochester, and the Huntington Study Group will evaluate the ability of HD-02 to slow functional decline in Huntington's disease patients. A Special Protocol Assessment will be submitted to expedite FDA review. The trial will be sponsored by the National Center for Complementary and Alternative Medicine of the National Institutes of Health (NIH) and the Orphan Product Division of the FDA. Enrollment is anticipated to begin in the third quarter of 2008. Source: PRNewswire 3/12/08

Postoperative Chemotherapy Does Not Improve Survival in Gastric Cancer Patients

The use of combination chemotherapy following surgery did not improve survival in patients with gastric cancer, according to a randomized clinical trial published online March 11 in the Journal of the National Cancer Institute. The only potentially curative therapy currently available for nonmetastatic gastric cancer is surgery. Recent studies have suggested that a combination of cisplatin, epirubicin, 5-fluorouracil, and leucovorin (PELF) improves outcome in patients with metastatic gastric cancer. To test the PELF combination in patients with localized disease, researchers at the University Hospital Careggi in Florence, Italy, and the Italian Oncology Group for Cancer Research conducted a randomized controlled trial in which 258 patients were treated with surgery or surgery followed by chemotherapy. With a median follow-up of 72.8 months, there was no significant difference in disease-free survival or overall survival between the two trial arms. Considering the negative results in this trial and other recent adjuvant chemotherapy trials in gastric cancer, the authors write, “Adjuvant chemotherapy alone remains a controversial approach in operable gastric cancer.” Source: EurekAlert! 3/11/08

Phase I Study of Treatment for Congestive Heart Failure Yields Positive Results

Palatin Technologies, Inc. announced in March that it had completed a Phase I clinical trial of PL-3994, a novel, long-acting natriuretic peptide receptor A agonist under development for treatment of acute decompensated congestive heart failure (CHF). The trial was a randomized, double-blind, placebo-controlled, single-ascending dose study in 26 healthy volunteers who received the medication or placebo subcutaneously. The evaluations included safety, tolerability, pharmacokinetics, and several pharmacodynamic endpoints, including levels of cyclic guanosine monophosphate, a natural messenger nucleotide. Dosing concluded with the successful achievement of the primary endpoint of the study, a prespecified reduction in systemic blood pressure. Data analysis is ongoing and will be submitted for presentation when the analysis is complete. The company plans to initiate a Phase IIa study in decompensated CHF later this year. Future plans include the development of PL-3994 for long-term administration in patients with chronic CHF and for the emergency treatment of severe acute systemic hypertension. Source: PRNewswire 3/10/08

Phase III Diabetic Nephropathy Trial Fails to Meet Primary Efficacy Endpoint

Keryx Biopharmaceuticals, Inc. in March announced that top-line results from its SUN-MICRO Phase III clinical trial of Sulonex (sulodexide) for the treatment of diabetic nephropathy failed to meet the primary objective of the study, which was to increase the proportion of patients that achieve therapeutic success at six months as compared to placebo over background therapy of maximal doses of ACE-inhibitors or ARBs. Therapeutic success was defined as (i) conversion from microalbuminuria to normoalbuminuria, as measured by albumin/creatinine ratio (ACR), with at least a 25 percent reduction in ACR relative to baseline ACR, or (ii) a 50 percent reduction in ACR relative to baseline ACR. In addition, in reviewing the mean changes in ACR over time, Sulonex and placebo appeared to be similar. The company plans to refocus its primary efforts and resources on rapidly moving one of its products, Zerenex, forward for end-stage renal disease patients with hyperphosphatemia, and another product, Perifosine, forward for cancer. The goal is to have Perifosine in a pivotal program this year and be well into a Zerenex high-dose Phase II trial before the end of the year. Source: PRNewswire 3/10/08

New Compound to be Studied in Phase I/II Trial for Aggressive Multiple Sclerosis

Cell Therapeutics, Inc. announced in March that its investigational drug pixantrone will be studied in a multicenter Phase I/II trial focused on aggressive relapsing remitting (RR) or secondary progressive (SP) multiple sclerosis (MS) and initiated by the Fondation Charcot Stichting, in Brussels, Belgium. The investigator-sponsored, open-label, noncomparative trial will enroll 20 patients in Belgium, France, and Germany with aggressive RR MS or SP MS who failed to respond to approved immunomodulatory agents (interferons, glatiramer acetate). The objectives of the study are to determine the efficacy of pixantrone as an immunosuppressive agent based on its ability to decrease the lymphocyte count and to evaluate efficacy in MS based on gadolinium-enhanced magnetic resonance imaging. According to the company, in addition to the potential for lower cardiac toxicity, preclinical studies suggest that pixantrone may provide more effective immune regulation than mitoxantrone, the only currently FDA-approved cytotoxic agent for treating MS. Meanwhile, a Phase III trial with pixantrone in relapsed aggressive non-Hodgkin's lymphoma is near completion. Source: PRNewswire 3/6/08

Trial Initiated for Treatment for Eosinophilic Esophagitis in Children

Ception Therapeutics, Inc. announced in March that it has initiated a multicenter Phase II/III clinical trial to evaluate reslizumab, a humanized monoclonal antibody against interleukin-5 (IL-5), for the treatment of eosinophilic esophagitis (EE) in pediatric patients. EE is a chronic inflammatory disease characterized by difficulty swallowing, vomiting, stomach or chest pain, and a failure to thrive. IL-5 is the major cytokine responsible for the eosinophilic inflammation of the esophagus seen in this condition. The FDA has granted orphan drug status to reslizumab for the treatment of pediatric EE. The study is a randomized, double-blind trial of reslizumab versus placebo in the treatment of approximately 172 patients with poorly controlled EE. Subjects will be randomized to one of three active dose groups or placebo, administered at monthly intervals for four months. The co-primary endpoints of the study are changes in clinical symptoms and esophageal eosinophil levels at the end of therapy. Therapies currently utilized for EE include severely restricted diets; there are no approved pharmacologic therapies for EE, although corticosteroids are sometimes administered to patients. Source: PRNewswire 3/5/08

Chemotherapy with Chemoradiation for Pancreatic Cancer has Small Survival Benefit

Adding gemcitabine (Eli Lilly’s Gemzar®) to chemoradiation for the treatment of patients who had surgery for pancreatic cancer was associated with a survival benefit, but this improvement was not statistically significant, according to a study in the March 5 issue of the Journal of the American Medical Association. Researchers at the University of Maryland Medical Center, Baltimore, assessed if adding the drug to the supplemental treatment of fluorouracil chemoradiation improved survival for patients who had pancreatic cancer surgery. The randomized, controlled Phase III trial included 451 patients enrolled at 164 U.S. and Canadian institutions, with follow-up through August 2006. Patients received chemotherapy with either fluorouracil or gemcitabine for three weeks prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy (with fluorouracil). Patients with pancreatic head (a part of the pancreas) tumors had a median survival of 20.5 months and three-year survival of 31 percent in the gemcitabine group versus 16.9 months and 22 percent in the fluorouracil group. Source: EurekAlert! 3/4/08

Phase I Trial Initiated for Novel Anti-Staphylococcal Antibiotic

Affinium Pharmaceuticals announced in March that it has commenced dosing healthy subjects in a Phase I study of AFN-1252, one of its lead clinical candidates from its novel class of fatty acid biosynthesis inhibitors. The study will evaluate the safety, tolerability, and pharmacokinetics of a single-escalating oral dose. The company is developing the antibiotic as an oral and intravenous treatment for susceptible and resistant staphylococcal infections, including hospital- and community-acquired methicillin-resistant Staphylococcal aureus. Oral bioavailability has previously been demonstrated in a human microdosing study, and in vivo efficacy has been demonstrated in various animal models of infection. According to the company, in preclinical studies, AFN-1252 was well tolerated at high multiples of the projected human dose in two species, suggesting a safety profile that would be attractive to physicians practicing both in and out of hospital settings. Unlike existing broad-spectrum products, the antibiotic utilizes a unique mechanism of action by directly inhibiting the function of the bacterial fatty acid synthesis II pathway. Source: PRNewswire 3/4/08

Candidate Granted U.S. Orphan Drug Status for the Treatment of Cystic Fibrosis

Mpex Pharmaceuticals, Inc. announced in March that the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development has granted an orphan drug designation for levofloxacin solution for inhalation for the treatment of pulmonary infections due to Pseudomonas aeruginosa and other bacteria in patients with cystic fibrosis (CF). The antibiotic levofloxacin is the active pharmaceutical ingredient in MP-376, the company's proprietary solution for inhalation. Orphan status is granted by the FDA to promote the development of products that demonstrate promise for the treatment of diseases affecting fewer than 200,000 Americans annually. Mpex recently completed a multicenter, 14-day, placebo-controlled clinical trial with MP-376 in 40 CF patients. Based on the results of the trial and consultations with the FDA and the Therapeutics Development Network of the Cystic Fibrosis Foundation, the company expects to initiate a Phase IIb clinical trial in approximately 140 CF patients in the second quarter of 2008. Several dosing regimens of MP-376 will be compared, including once-daily administration schedules. Source: PRNewswire 3/4/08

Breast Cancer Treatment May be Effective Against Mania in Patients with Bipolar Disorder

A small trial of tamoxifen, a drug typically used to treat breast cancer, indicates that it also may decrease symptoms of mania in patients with bipolar disorder, according to a report in the March issue of Archives of General Psychiatry. Tamoxifen inhibits the actions of a family of enzymes known as protein kinase C. Abnormal levels of activity by these enzymes have been associated with bipolar disorder and related dysfunctions, such as distractibility, impaired judgments, and disorganized thoughts. Researchers at the Dokuz Eylül University Medical School in Turkey conducted the trial with 66 patients who were randomly assigned to take tamoxifen (40 mg to 80 mg per day) or identical placebo tablets twice daily for up to three weeks. A total of 50 patients—29 assigned to take tamoxifen and 21 assigned to take placebo—completed the trial. Patients in the tamoxifen group had significantly lower scores on tests used to measure the severity of mania at the end of the three-week period, while those in the placebo group had scores that slightly increased. Almost half of patients taking tamoxifen responded to the drug—defined as a reduction of at least half in mania scores. Source: Newswise 3/3/08

Trial Shows Reduction in Mortality for Children with Severe Langerhans Cell Histiocytosis

A new international study found that introducing an increased intensity of chemotherapy in children with severe Langerhans cell histiocytosis (LCH) can reduce the mortality rate for this disorder by as much as 20 percent when the patient demonstrates a rapid response to such treatment. The study, published in the March 1 edition of Blood, is the second in a series of international randomized clinical trials for Langerhans cell histiocytosis coordinated by the Histiocyte Society. The LCH clinical trial series are the first-ever randomized clinical trials for the treatment of LCH. The trial induced a rapid response to the application of chemotherapy—involving prednisone, vinblastine, and for some participants, the addition of etoposide. As a result, the research team observed a statistically significant improved prognosis for children with multisystem LCH. Study leaders observed this significant effect in both study groups of the second clinical trial. The results were based on the findings in 193 “risk patients”—those with LCH affecting risk organs including the liver, lungs, hematopoietic system, and spleen, or patients with disease onset younger than 2 years of age. Source: EurekAlert! 3/1/08

Drug Significantly Extends Progression-Free Survival in Advanced Kidney Cancer Patients

An independent data monitoring committee stopped a Phase III clinical trial of Novartis’ investigational drug everolimus (RAD001) in February after interim results showed significantly better progression-free survival in patients with advanced kidney cancer who received everolimus compared to placebo. The committee stopped the trial of more than 400 patients conducted in 12 countries because the study met its primary endpoint. The interim findings are being shared with investigators to allow them to offer everolimus to patients remaining on placebo. Everolimus may fulfill an unmet medical need for patients with advanced renal cell cancer (RCC) who currently have no approved treatment options. The once-daily oral therapy inhibits the mTOR protein, a central regulator of tumor cell division and blood vessel growth in cancer cells. The randomized, double-blind trial included patients who had their cancer worsen despite receiving approved treatments for RCC. In addition to RCC, everolimus is being evaluated in neuroendocrine tumors, lymphoma, other cancers, and tuberous sclerosis, as a single agent or in combination with existing cancer therapies. Source: PRNewswire 2/28/08

Enrollment Completed for Phase IIa Hypertension Study

Pharmacopeia in February announced that it had completed recruitment for a multicenter Phase IIa clinical study of PS433540, the dual-acting angiotensin and endothelin receptor antagonist that is the company’s lead internal product candidate for hypertension and diabetic nephropathy. The objective of the randomized, double-blind, placebo-controlled, parallel-group study is to evaluate the efficacy and safety of 200 and 500 mg of PS433540 in subjects with Stage I and Stage II hypertension. The company expects to report results in the second quarter of 2008 from this, the first PS433540 study to include hypertensive patients. Results from Phase I studies in normal subjects have indicated that the compound was well tolerated at all doses up to and including 1,000 mg a day for 14 days. Several studies, including multiple ascending dose and angiotensin II challenge studies, have shown that PS433540 appears to have a pharmacokinetic profile consistent with once-daily oral administration. Source: PRNewswire 2/26/08

Recruitment Begins for Trial of New Gel for Chronic Diabetic Foot Ulcers

Associated Foot & Ankle Specialists in February announced that it is recruiting patients with foot ulcers due to diabetes to participate in Cardium Therapeutics’ MATRIX Phase IIb clinical trial, which will study the effects of a new topical gel product, Excellarate, for the potential treatment of patients with nonhealing diabetic foot ulcers. The trial is a randomized, double-blind, safety and efficacy research study in which the product is administered once or twice over the course of the study, with a goal of complete ulcer closure at 12 weeks or earlier. The gel is designed to provide release of the platelet-derived growth factor BB protein, which stimulates angiogenesis (the growth of new blood vessels) and granulation tissue formation, the building blocks for a variety of wound-healing processes. Many diabetic patients suffer from peripheral neuropathy, or a loss of feeling in their feet, that puts them at increased risk of foot ulceration. Patients with nonhealing ulcers are more susceptible to infections that may lead to amputation of the affected foot or leg. Associated Foot & Ankle Specialists is among 25 sites participating in the MATRIX trial, which is expected to enroll 210 patients nationwide. Source: PRNewswire 2/25/08

Anti-HIV Gel Proven Safe and Tolerable for Women

An experimental anti-HIV gel is safe for women to use on a daily basis, researchers at the University of Alabama at Birmingham and the University of Pittsburgh School of Medicine announced in February. In testing, the gel, called tenofovir, was favorably self-applied and tolerable to non–HIV-infected women, a significant boost to HIV and AIDS prevention efforts focused on next-generation microbicides to reduce infection rates, the researchers said. The tenofovir Phase II trial results were presented at an international microbicides meeting in New Delhi, India. The researchers are part of the U.S. National Institutes of Health–funded Microbicide Trials Network, an international team of researchers devoted to exploring and evaluating anti-HIV microbicides. Researchers evaluated if tenofovir was safe to use every day for six months, or safe to use prior to each act of intercourse. They found both approaches equally safe. The study included 200 sexually active HIV-negative women who were asked to use condoms in addition to the gel. Tenofovir was developed by Gilead Sciences, Inc. Source: Newswise 2/25/08

Company Shifts Focus to Other Products Following Closure of African Sleeping Sickness Trial

Immtech Pharmaceuticals, Inc. in February announced that the company will focus on its new drug discovery programs targeting hepatitis C and drug-resistant bacterial and fungal infections, and will discontinue all development programs for pafuramidine maleate, a therapy that it had been studying for African sleeping sickness. The decision was made in response to recent reports related to additional events identified in a cohort of volunteers in a safety study involving the drug. According to the company’s announcement, the cause of the liver and kidney abnormalities in the volunteers is still a matter of speculation, and additional time and resources will be used to further examine these abnormalities. However, Immtech believes that the potential risk associated with further treatment of African sleeping sickness patients outweighs the benefits of further development because these patients are generally located in places where medical care may not be readily available. Additionally, the potential benefit and resources required relative to potential risk to pneumocystis pneumonia patients do not support further development for this target market. Immtech was informed in late December 2007 that a subgroup of volunteers in the safety study who were treated with pafuramidine experienced liver abnormalities. In response to that finding, Immtech announced that all clinical trials involving pafuramidine would be placed on clinical hold pending completion of a comprehensive analysis. All volunteers now have normal liver function. However, this month, Immtech received reports of additional events related to abnormal kidney function of volunteers from the same safety study. The affected safety study volunteers are receiving full follow-up monitoring and medical care. Source: PRNewswire 2/22/08

Financing Supports Study of Test for Measuring Response to Antiplatelet Drugs

Accumetrics, Inc. announced in February that it has raised $28.8 million in its Series D financing to support the study of its VerifyNow® family of tests for measuring patient response to antiplatelet drugs. Under the direction of the Scripps Advanced Clinical Trials center, the company is sponsoring a 6,000-patient, multicenter trial to establish platelet function testing with VerifyNow as the standard of care. According to the company’s announcement of the financing, the project supports the concept of individualized medicine, as not everyone responds the same way to current antiplatelet medications. The company anticipates that the results of the trial will help physicians make clinical decisions to maximize safety and improve outcomes for a large number of patients on such therapy. Source: PRNewswire 2/21/08

Personalized Immunotherapy Data Show Improved Survival Rates for Brain Cancer Patients

Northwest Biotherapeutics, Inc. in February announced the most recent long-term follow-up data, as of year-end 2007, on disease progression and overall survival in patients taking part in its Phase I and Phase I/II clinical trials for newly diagnosed patients with Glioblastoma multiforme (GBM), the most aggressive form of brain cancer. The additional data cover the period from April 2007 through year-end 2007. During this time, none of the patients experienced disease progression (recurrence) and only one patient died (at 36.4 months). Thus, the data show that in the 19 clinical trial patients receiving injections of the personalized immunotherapy DCVax®-Brain in addition to standard-of-care, both the median overall survival and the median time to recurrence are more than twice as long as in patients receiving the standard-of-care for GBM. Among other findings as of the end of 2007, eight of the 19 patients were still alive (ranging from 24.5 months to 92 months), with median overall survival in all patients of 33.8 months; five of the eight patients showed no signs of cancer recurrence, with follow-up time ranging from 41 months to 92 months; and 68 percent of patients receiving DCVax®-Brain in addition to standard-of-care have lived longer than two years, 42 percent longer than three years, and 26 percent longer than four years. The company has initiated a large Phase II trial of the product that is designed and powered to serve as a pivotal trial in support of potential product registration. The trial is currently screening and enrolling patients at a number of sites across the United States. Source: PRNewswire 2/20/08

Trial Launched for New Retinoic Acid Formulation

Phosphagenics Limited in February announced the initiation of a human clinical trial for its lead dermatological product, retinoic acid, a form of vitamin A. This trial represents the company's first clinical trial to take place in the United States and denotes the commencement of the company's planned expansion into targeted, nonsystemic delivery of drugs. The trial follows a number of preclinical studies that demonstrated both an increase in dermal absorption of retinoic acid when formulated with Phosphagenics' proprietary drug delivery platform, and a significant reduction in irritation scores. The clinical trial is a double-blinded study that will involve 90 subjects and is being conducted by cyberDERM Inc., a contract research organization. This trial is expected to be completed by the end of the second quarter of 2008. Source: PRNewswire 2/19/08

Phase III Lung Cancer Trial Stopped Early

Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc. in February announced that a Phase III trial evaluating Nexavar® (sorafenib) tablets in patients with nonsmall-cell lung cancer (NSCLC) was stopped early following a planned interim analysis, when the independent data monitoring committee (DMC) concluded that the study would not meet its primary endpoint of improved overall survival. The trial evaluated Nexavar when administered in combination with the chemotherapeutic agents carboplatin and paclitaxel. Safety events were generally consistent with those previously reported. However, higher mortality was observed in the subset of patients with squamous cell carcinoma of the lung treated with sorafenib and carboplatin and paclitaxel versus those treated with carboplatin and paclitaxel alone. Bayer and Onyx are providing information regarding this DMC recommendation to health authorities and those clinical investigators involved in studies of Nexavar. In addition, the companies will further review the findings of this analysis and DMC recommendation to determine what, if any, impact they have on other ongoing Nexavar lung cancer trials. Data from this study will be presented at an upcoming scientific meeting. The multicenter, randomized, double-blind, placebo-controlled study enrolled more than 900 patients at more than 140 clinical sites in North America, South America, Europe, and the Asia Pacific region. Source: PRNewswire 2/18/08

European Trial Announced for Retinal Implant to Treat Blindness

The University of Southern California and Second Sight Medical Products Inc. announced in February that they have completed enrollment of the first phase of a U.S. Food and Drug Administration–approved clinical study of the Argus II Retinal Prosthesis System. They also announced that enrollment at key European sites is under way as studies continue in Mexico. The Argus II is the second generation of an electronic retinal implant designed for the treatment of blindness due to retinitis pigmentosa, a group of inherited eye diseases that affect the retina. The implant consists of an array of 60 electrodes that are attached to the retina. These electrodes conduct information acquired from an external camera to the retina to provide a rudimentary form of sight to implanted subjects. Ten subjects were recruited for the Phase I trial at four leading ophthalmic centers throughout the U.S., including the Doheny Eye Institute at the University of Southern California, Wilmer Eye Institute at Johns Hopkins University, the University of California at San Francisco, and the Retina Foundation of the Southwest. Second Sight will seek expansion of the U.S. trial to include other trial sites located at Columbia University Medical Center and Lighthouse International in New York, Scheie Eye Institute and Wills Eye Hospital in Philadelphia, and Emory University and Atlanta V.A. Rehab R&D Center in Atlanta. This three-year Investigational Device Exemption trial is the only long-term study of a retinal prosthesis currently being conducted anywhere in the world. Source: EurekAlert! 2/15/08

Pivotal Trial Completed for Type 2 Diabetes Treatment

Keryx Biopharmaceuticals announced in February that the last subject randomized into the SUN-Micro Phase III clinical trial has completed the scheduled eight-month visit. This milestone officially marks the completion of this pivotal clinical trial of the company’s investigational drug Sulonex™ (sulodexide oral gelcap) in the treatment of subjects with Type 2 diabetes and persistent microalbuminuria despite treatment with the maximum approved or tolerated dose of either an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. This randomized, double-blind, placebo-controlled study enrolled 1,056 subjects at more than 150 sites worldwide. The company expects to report top-line results from this study before the end of March, and to file a New Drug Application with the U.S. Food and Drug Administration (FDA) before the end of the year. The overall Phase III and IV program for the product is being investigated under a Special Protocol Assessment with the FDA, and the trials are conducted by the Collaborative Study Group, the world's largest standing renal clinical trials group. Source: PRNewswire 2/11/08

Extracellular Inhibitor of HIV Infection Proceeds to Phase III

Schering-Plough Corp. in February reported that the final results of a Phase II clinical study showed vicriviroc, its investigational CCR5 antagonist, demonstrated potent and sustained viral suppression through 48 weeks of therapy in treatment-experienced, HIV-infected patients when administered once daily as a single tablet in combination with an optimized, ritonavir-boosted protease inhibitor containing antiretroviral regimen. Vicriviroc is a next-generation extracellular inhibitor of HIV infection designed to block entry of infectious virions into uninfected CD4 cells via antagonism of the CCR5 co-receptor. In the study, significantly more patients who added vicriviroc 30 mg once daily to a new optimized background therapy (OBT) had fully suppressed HIV-RNA (less than 50 copies/ml) at 48 weeks compared to patients receiving new OBT alone (56 percent versus 14 percent). A total of 116 treatment-experienced, adult, HIV-infected patients with R5-type virus at screening were randomized in the placebo-controlled, double-blind study at 37 sites throughout Europe, South Africa, North America, and South America. The results supported the selection of the 30 mg once-daily vicriviroc dose for use in ongoing Phase III clinical studies that are currently enrolling approximately 375 patients each at more than 160 sites in North America, Latin America, Europe, Australia, and South Africa. Source: PRNewswire 2/6/08

Novel Small Molecule Therapy Shows Benefit for Anemic Patients

According to a study in Blood, the official journal of the American Society of Hematology, a novel small molecule therapy from Icagen, Inc. called senicapoc showed efficacy in maintaining hydration of red blood cells and increasing hemoglobin levels in patients with sickle cell anemia. Research suggests that dehydration of the red blood cells is one of the key contributors to the deformed cell shape that is seen in sickle cell anemia and that affects the levels of circulating hemoglobin, an important determinant of oxygen delivery throughout the body. The dehydration appears to result from loss of potassium via two pathways, one of which is known as the Gardos channel. Senicapoc, a known Gardos channel blocker, works by limiting solute and water loss, thereby preserving red blood cell hydration. In a 12-week, multicenter, Phase II, randomized, double-blind, dose-finding study, senicapoc was evaluated for its effect on hemoglobin level and markers of red blood cell destruction (hemolysis) in 90 patients. The investigators also sought to obtain additional safety data and identify the optimal dose for a Phase III study. The primary efficacy endpoint was the change in blood hemoglobin level from baseline to end of study, and secondary endpoints included markers of hemolysis, changes in red blood cell count and indices, and frequency of painful events or "crises." Source: EurekAlert! 2/5/08

Largest Study Ever Completed in Osteosarcoma Patients Highlights Orphan Drug

IDM Pharma, Inc. in February announced that long-term follow-up of 662 osteosarcoma patients in a Phase III trial of the orphan drug mifamurtide (L-MTP-PE) showed that adding the drug to chemotherapy following surgery resulted in statistically superior overall survival. The trial—the largest ever completed in this disease—was a National Cancer Institute−funded cooperative group study conducted by the Children's Oncology Group. In the past two decades, there have been no treatment advances for patients with osteosarcoma, a rare and often fatal bone tumor that typically affects children and young adults. The multicenter, open-label, randomized, factorial, four-parallel-treatment-group study was designed to evaluate the effects of patient outcome of the addition of L-MTP-PE to three-drug chemotherapy (cisplatin, doxorubicin, and methotrexate) or four-drug chemotherapy (cisplatin, doxorubicin, methotrexate, and ifosfamide) in patients with newly diagnosed resectable osteosarcoma without metastatic disease. Overall survival after six years of follow-up in patients treated with chemotherapy and L-MTP-PE was 78 percent, compared to 70 percent in patients treated only with chemotherapy. The addition of L-MTP-PE to chemotherapy resulted in an approximately 30 percent decrease in the risk of death. Source: PRNewswire 2/4/08

Phase III Data Show Long-Term Improvement of Chronic Plaque Psoriasis

One-year data from a double-blind, placebo-controlled Phase III study showed that therapy with Centocor’s ustekinumab given every 12 weeks provided sustained, clinically meaningful improvement in the treatment of moderate-to-severe plaque psoriasis through one year. According to findings presented at the Annual Meeting of the American Academy of Dermatology, 87 percent of patients responding to ustekinumab 45 mg maintenance therapy, and 91 percent of patients responding to ustekinumab 90 mg maintenance therapy, sustained at least a 75 percent improvement in psoriasis through one year. Ustekinumab is a new human monoclonal antibody with a novel mechanism of action that targets the cytokines interleukin-12 and interleukin-23, naturally occurring proteins that are important in the body’s regulation of immune responses and that are also believed to play a role in immune-mediated inflammatory disorders, including psoriasis. The trial evaluated the efficacy and safety of ustekinumab in the treatment of 766 patients who were randomized to receive subcutaneously administered ustekinumab or placebo. Source: EurekAlert! 2/2/08

Integrated Analysis Reveals High Level of Skin Clearance from Established Psoriasis Drug

Data from an integrated analysis of three trials showed that patients with moderate-to-severe plaque psoriasis receiving another Centocor drug, the already marketed Remicade® (infliximab), achieved a consistently high level of skin clearance in each of the four body regions (head, trunk, lower extremities, and upper extremities). At week 10 of the analysis, which included nearly 1,500 subjects, 71 percent of patients receiving Remicade 3 mg/kg and 79 percent of patients receiving 5 mg/kg achieved at least a 75 percent improvement in the chronic inflammatory condition, compared to 3 percent of patients receiving placebo. Additionally, 39 percent and 52 percent of patients receiving 3 mg/kg and 5 mg/kg, respectively, achieved nearly complete skin clearance, versus 1 percent of patients receiving placebo. Investigators reported these findings at the 66th Annual Meeting of the American Academy of Dermatology. Two of the trials were Phase III, multicenter, randomized, double-blind, placebo-controlled studies that evaluated the safety and efficacy of Remicade induction and maintenance therapy in 378 and 835 adult patients with chronic, stable plaque psoriasis involving at least 10 percent of their body surface area. A third trial was a Phase II, multicenter, double-blind, placebo-controlled study of 249 patients with severe plaque psoriasis who had previously received psoralen plus ultraviolet light A or systemic therapy for psoriasis. Source: EurekAlert! 2/1/08

Drug May Significantly Improve Treatment of Dangerous Blood Disorder

Two clinical trials of Amgen, Inc.’s novel drug romiplostim (Nplate) show that it significantly improved platelet levels in patients with chronic immune thrombocytopenic purpura (ITP), a hematologic disorder that can cause uncontrolled bleeding. In the February 2 issue of The Lancet, an international research team reports Phase III trial results for the drug, which duplicates the action of a natural hormone discovered by a Massachusetts General Hospital investigator. Currently available treatments for ITP—including steroid drugs, which have significant side effects, and removal of the spleen (splenectomy)—are designed to reduce platelet destruction and may be ineffective in many patients. Thrombopoietin is the natural regulator of platelet production, and romiplostim is a unique peptide antibody that stimulates platelet production by mimicking the action of thrombopoietin. The double-blinded Phase III trials were conducted at 35 sites in the United States and Europe. One trial enrolled 63 splenectomized patients and the other included 62 patients who retained their spleens. Among the 42 splenectomized patients who received romiplostim, nearly 80 percent reached the target platelet count during at least four weeks of the 24-week study, and 38 percent achieved a durable response, maintaining a target platelet count during at least six of the last eight weeks of the study. In the nonsplenectomized patients, 88 percent had at least four target platelet count measurements, with 61 percent achieving a durable response. More than half of the patients receiving romiplostim were able to discontinue all other ITP medications they were taking, and 35 percent reduced other therapies. While more than half the participants in the placebo groups of both studies needed rescue medications to treat or prevent bleeding episodes, significantly fewer of those receiving the active medication needed such treatment. Source: EurekAlert! 1/31/08

Enrollment Opened in Phase II Clinical Trial for Patients with Advanced Breast Cancer

Peregrine Pharmaceuticals, Inc. in late January announced that patient screening has begun in a clinical trial designed to evaluate the safety and efficacy of bavituximab in combination with chemotherapy in patients with advanced breast cancer. The primary objective of the study is to assess the overall response rate to the combination of bavituximab with docetaxel, a chemotherapy drug commonly used in advanced breast cancer. The multicenter clinical trial is being conducted in the Republic of Georgia. In the trial's two-stage design, up to 15 patients with advanced breast cancer will be enrolled initially. If promising results are observed, the study will be expanded up to a total of 46 patients. Patients may continue to receive bavituximab alone after completion of chemotherapy, as long as the cancer does not progress and side effects are acceptable. Bavituximab is a monoclonal antibody that binds to a phospholipid called phosphatidylserine, which is usually located inside normal cells, but which becomes exposed on the outside of the cells that line the blood vessels of tumors, creating a specific target for anticancer treatments. Bavituximab is believed to help mobilize the body's immune system to destroy the blood vessels needed for tumor growth and spread. In a Phase lb pilot trial in advanced cancer patients, bavituximab plus chemotherapy appeared to have a safety profile consistent with chemotherapy alone and showed positive signs of clinical activity, achieving objective response or disease stabilization in 50 percent of the evaluable patients. Peregrine has received regulatory approval to conduct two additional Phase II trials: one to study bavituximab in breast cancer and the other in nonsmall cell lung cancer—both in combination with carboplatin plus paclitaxel. Bavituximab is in clinical trials in the U.S. in patients with advanced solid tumors and in patients coinfected with HCV and HIV. Source: PRNewswire 1/29/08

Bone-Building Drug Approved for First-in-Human Trials

Velcura Therapeutics Inc. recently completed a successful Investigational New Drug application to the U.S. Food and Drug Administration and will proceed with the first-in-human clinical trials for its lead compound, VEL-0230. According to the company, the new chemical entity stimulates bone formation, inhibits bone loss, and reduces plasma calcium levels. The company plans to investigate VEL-0230 as an orally available molecule for the treatment of diseases involving bone mineral disorders, such as bone loss related to multiple myeloma, bone metastases, rheumatoid arthritis, and osteoporosis. The first phase of clinical trials in humans is planned to begin at the end of February. Source: PRNewswire 1/28/08

Company Plans to Initiate Phase III Trial of Alzheimer's Disease Treatment in Second Quarter of 2008

Medivation, Inc. in January announced that, based on its end-of-Phase II meeting with the U.S. Food and Drug Administration (FDA), the company plans to begin a pivotal confirmatory Phase III trial of Dimebon™ for mild-to-moderate Alzheimer's disease in the second quarter of 2008. The FDA informed Medivation that the company's previously completed trial conducted in Russia can be used as one of the two pivotal studies required to support the approval of Dimebon for the same indication, as long as a significant proportion of the sites in the new trial are located in the United States. The trial will enroll approximately 525 patients at U.S., European, and South American sites. Patients will be randomized to one of three treatment groups, including two arms for different doses of the drug and one for placebo, and treated for six months. The company expects to complete the trial and apply for marketing approval in 2010. Source: PRNewswire 1/28/08

Positive Safety Data Support Ongoing Phase II Trial for Colorectal Cancer Treatment

Poniard Pharmaceuticals, Inc. in January presented safety data from a Phase I dose-escalation study of picoplatin, a platinum-based chemotherapeutic, at the 2008 Gastrointestinal Cancers Symposium, a meeting of the American Society of Clinical Oncology. The poster presentation included safety data on 50 patients regarding picoplatin in combination with 5-fluorouracil (5FU) and leucovorin (LV) as a first-line treatment for metastatic colorectal cancer (mCRC). Promising safety data observed from the study to date formed the basis for further development of picoplatin in the company’s ongoing Phase II trial. According to the company, the results suggest that picoplatin does not cause severe neurotoxicity, as is commonly seen in mCRC patients treated with the regimen of 5FU and LV with oxaliplatin (sanofi-aventis’ Eloxitan®). The company initiated a randomized Phase II trial in November 2007 to evaluate intravenous picoplatin in the first-line treatment of mCRC, and expects to present data from the Phase I and II mCRC program in scientific forums later this year. Poniard also is evaluating the drug in intravenous form in an ongoing pivotal Phase III trial for the treatment of small cell lung cancer and in an ongoing Phase II trial for the treatment of hormone refractory prostate cancer. Oral picoplatin is being evaluated in a Phase I trial in solid tumors. Source: PRNewswire 1/27/08

Early Promising Results in Malaria Vaccine Trial in Mali

A small clinical trial conducted by an international team of researchers in Mali has found that a candidate malaria vaccine developed by the Walter Reed Army Institute of Research and GlaxoSmithKline was safe and elicited strong immune responses in the 40 Malian adults who received it. The trial was the first to test this vaccine candidate, which is designed to block the malaria parasite from entering human blood cells, in a malaria-endemic country. Based on these promising results, the research team is now conducting trials of the vaccine in 400 Malian children aged 1 to 6 years. The work was based at the Malaria Research and Training Center at the University of Bamako, Mali, and supported by the U.S. National Institute of Allergy and Infectious Diseases. A total of 60 participants were assigned at random to receive either a full or half-dose of the candidate malaria vaccine or a licensed rabies vaccine, which served as a control. Those who received the candidate vaccine tolerated it very well and experienced a significant boost (up to a sixfold rise) in levels of vaccine-specific antibodies. Source: EurekAlert! 1/22/08

FDA Grants Approval to Extend U.S. Enrollment and Clinical Trial

Ablation Frontiers, Inc. in January announced the expansion of enrollment in the first-ever U.S. Investigational Device Exemption clinical trial for interventional treatment of chronic atrial fibrillation (AF). Approval from the U.S. Food and Drug Administration (FDA) to proceed with the pivotal phase of the study is based on the review of an initial feasibility segment completed in August 2007. Several patients have already been randomized into the study. Initial U.S. treatment sites included the Lahey Clinic and Medical Center in Burlington, Mass., where the first patient, with a three-year history of continuous AF, was successfully treated and returned home the next day with a normal heart rhythm. The Cardiac Ablation System being evaluated combines a novel radiofrequency energy source with a series of anatomically designed catheters. For every two patients initially receiving an ablation, one will be randomly assigned to the control arm with drug therapy. The trial allows patients in the control arm to receive an ablation if they do not respond to drug therapy. Source: PRNewswire 1/16/08

Phase l Results Bode Well for Novel Antidepressant Agent

CeNeRx BioPharma, Inc. in January announced the successful completion of the Phase l clinical program for Tyrima™, its lead candidate for the treatment of depression and anxiety. Tyrima is a selective and reversible member of a novel class of drugs known as reversible inhibitors of monoamine oxidase A (RIMAs). The Phase l program included acute dose, repeat dose, and fed-fasted studies. The results of all studies were favorable, showing that the drug was safe and well tolerated and exhibited good pharmacokinetic properties. The drug elevates the levels of the neurotransmitters serotonin, norepinephrine, and dopamine, all of which affect mood and anxiety. The Phase l program evaluated a range of doses in 65 subjects. The repeat dose study results confirmed the positive findings of an acute dose trial that were reported previously. The company expects to initiate a Phase ll program in the second quarter of 2008. This compound, which could be the first RIMA antidepressant available in the U.S. market, has patent protection beyond 2027. Source: PRNewswire 1/16/08

Leading Hepatitis C Therapies Compared

Schering-Plough Corp. in January reported top-line results of the first large, randomized clinical study comparing the leading therapies for chronic hepatitis C: Schering-Plough’s Pegintron™ (peginterferon alfa-2b) and Rebetol® (ribavirin, USP) combination therapy versus Roche’s Pegasys (peginterferon alfa-2a) and Copegus® (ribavirin, USP) combination therapy, as well as a lower dose of Pegintron in an investigational combination regimen. The results showed that sustained virologic response (SVR), the primary endpoint of the study, was similar for the two leading combination therapies for hepatitis C, and that using a lower dose of Pegintron with Rebetol resulted in a similar SVR. The study also showed that fewer patients treated with both Pegintron regimens relapsed after the end of treatment compared to those receiving Pegasys and Copegus. The Phase IIIb, randomized, parallel-group study was conducted at 118 academic and community centers across the United States, and treated 3,070 adult patients with chronic hepatitis C virus genotype 1. Source: PRNewswire 1/14/08 Also see Roche’s response here.

Mixed Results Announced for Phase III Trials on Intravenous Painkiller

Cadence Pharmaceuticals, Inc. in January announced top-line results of two of the company's four pivotal Phase III clinical trials of Acetavance™, a formulation of acetaminophen for intravenous use. One of these clinical trials did not meet its primary endpoint of demonstrating a statistically significant reduction in patients' pain intensity levels over 48 hours compared to placebo following abdominal gynecologic surgery. However, this same study achieved several secondary endpoints, including pain relief, global patient satisfaction, and time to rescue medication. Cadence also announced that its Phase III clinical trial of Acetavance in fever met the primary endpoint of demonstrating a statistically significant reduction of fever over six hours compared to placebo. The abdominal gynecologic surgery trial was a randomized, double-blind, placebo-controlled, multiple-dose study of 331 patients at 27 clinical sites in the United States. The fever trial was a randomized, double-blind, placebo-controlled study of 60 adult patients at one U.S. site. Source: PRNewswire 1/11/08

Study Highlights Alternative to Drug-Eluting Stents

Patients who received OrbusNeich's Genous Bio-engineered R stent had significantly fewer major cardiac adverse events (MACE) than those who received Boston Scientific's Taxus or Johnson & Johnson's Cypher drug-eluting stents in a study of 195 high-risk patients who underwent percutaneous coronary intervention at Federico II University of Naples in Italy. At clinical follow-up of 10 months, the cumulative MACE rate for the Genous group (GRS) was 4 percent versus 22 percent for the combined Taxus and Cypher group (DES). For the MACE components, the cumulative rate of target vessel revascularization was 1 percent for GRS versus 11.8 percent for DES; the cumulative rate of myocardial infarction was 1 percent for GRS versus 7.8 percent for DES; and the cumulative mortality rate was 2 percent for GRS versus 7.8 percent for DES. Also, the cumulative rate for stent thrombosis was 2 percent for GRS versus 5.8 percent for DES. Unlike stents that elute cytotoxic agents to inhibit neointimal proliferation, Genous attracts circulating endothelial progenitor cells to rapidly build a layer of healthy tissue and promote long-term, natural healing. Source: PRNewswire 1/10/08

Phase IIa Study Paves Way for New Trial of Heart Attack Prevention Drug

deCODE genetics in January announced positive top-line results from its Phase IIa clinical trial for DG051, a leukotriene A4 hydrolase inhibitor being developed for the prevention of heart attack. In several studies conducted in healthy volunteers last year, DG051 was shown to reduce the production of leukotriene B4 (LTB4) in a dose-dependent manner. LTB4 is a pro-inflammatory molecule that deCODE's gene discovery and functional biology work identified as one of the factors modulating risk of heart attack. The results of the double-blind, placebo-controlled study confirm that DG051 delivers significant dose-dependent reductions in LTB4 in patients with a history of heart attack or coronary artery disease and who were taking a variety of concomitant medications. A Phase IIb trial will begin in the spring as a 400-patient, double-blind, placebo-controlled study further examining the drug’s pharmacokinetic and pharmacodynamic parameters, as well as safety and tolerability. Source: PRNewswire 1/9/08

Hypertension Treatment to be Studied Further this Year

Surface Logix in January announced that its randomized, double-blind, placebo-controlled, crossover Phase IIa study in 60 patients with uncontrolled hypertension at two European centers demonstrated that SLx-2101 caused clinically significant reductions in blood pressure and was well tolerated in repeat oral doses once daily for up to 14 days. The company plans to initiate a Phase IIb study in the third quarter of 2008. SLx-2101 is an oral, potent, selective, fast-onset, long-acting PDE5 inhibitor. Other PDE5 inhibitors have traditionally been used to treat erectile dysfunction. According to the company, the drug is uniquely positioned among the known PDE5 inhibitors to address cardiovascular disease because, compared to currently marketed PDE5 drugs, SLx-2101 preferentially distributes into cardiovascular tissue. The drug achieves sustained plasma levels without showing accumulation upon repeat dosing, which leads the company to say that daily or on-demand dosing can be undertaken with a predictable response in a number of cardiovascular disorders that currently marketed PDE5 therapies cannot adequately address. Source: PRNewswire 1/8/08

Newer Meningitis Vaccine Appears Safe and Effective for Infants

A vaccine not yet licensed in the United States produces immunity against four strains of meningococcal disease and is well tolerated when administered to infants, according to a study in a recent issue of the Journal of the American Medical Association. Researchers based in England conducted a randomized, controlled study to determine the immunogenicity of a novel tetravalent meningococcal vaccine known as MenACWY in 421 healthy infants in the United Kingdom and Canada. The infants received one of three different dosing schedules of MenACWY or a monovalent vaccine against the meningitis C serogroup. The study found that at least 92 percent of infants on a two-, three-, four-month dosing schedule had protective antibody levels to all four serogroups. In a two-, four-, six-month schedule, similar results were obtained for the C, W-135, and Y serogroups, but the proportion of infants with protective antibody levels against serogroup A only reached 81 percent. In the two-, four-month primary series groups, at least 84 percent had protective antibody levels to three of the four serogroups, while 60 to 66 percent of infants had protective levels against serogroup A. After a booster dose at 12 months, at least 95 percent developed protective antibody levels to three of the four serogroups, and 84 percent for serogroup A. Source: EurekAlert! 1/8/08

Company Concludes Enrollment in Trial for Acute Spinal Cord Injury

Alseres Pharmaceuticals, Inc. announced in January that it has concluded enrollment in the open-label, nonplacebo-controlled, dose-escalating Phase I/IIa clinical trial of the drug Cethrin for acute spinal cord injury. A total of 48 subjects have been enrolled at nine sites in the United States and Canada, and the company says that the rate and magnitude of improvement of many subjects seems greater than the expected pattern of recovery thus far. Alseres intends to move forward with its previously announced plans for a placebo-controlled Phase IIb trial at sites in the U.S., Canada, Euro