Gene Therapy Shows Promise for Rare Childhood Blindness

By Tracy Trundle

Targeted Genetics reported positive results from a phase I/II trial of its RPE65 gene therapy for the treatment of retinal dystrophy due to Leber’s congenital amaurosis (LCA). LCA is a rare eye disease that causes severe vision loss or blindness. The disease is genetically inherited and usually manifests itself at birth or in early infancy. There are thought to be 3,000 people in the U.S. with the disease; however, the technology has the potential to treat a variety of eye diseases such as macular degeneration which afflicts 1.25 million people in the U.S. alone.

The single-center, open label study enrolled nine young adults, between the ages of 17 and 23 years, with early-onset severe retinal dystrophy due to LCA.

The subjects were administered a single retinal injection of the Adeno-Associated Virus (AAV) vector expressing RPE65. In each subject, the eye with the worse acuity was selected as the study eye and the other was used as a control. After two weeks, data from the first three treated subjects showed that they had improved vision in the injected eye and could read several lines on an eye chart.

They also had less nystagmus (or involuntary eye movement) after six months and one subject showed a significant consistent improvement in visual function and subjective tests of visual mobility.

No adverse events or inflammation were reported. Based on the results the company planned to enroll additional subjects into the trial.

The study, called "Effect of Gene Therapy on Visual Function in Leber's Congenital Amaurosis," by Bainbridge, et al., conducted in collaboration with University College London and Moorfields Hospital, will appear in the May 22nd issue of the New England Journal of Medicine (JAMA). The full results of the trial were also presented at the Association for Research in Vision and Ophthalmology (ARVO) 2008 Annual Meeting in Fort Lauderdale, Fla.

Tracy Trundle is a Research Analyst at CenterWatch.

NPS Pharmaceutical in Talks with FDA After More Positive Results with Gattex

By Tracy Trundle

NPS Pharmaceuticals issued positive results from a phase III extension study of Gattex (teduglutide), an injectable glucagon-like peptide-2 (GLP-2) analog, for the treatment of short bowel syndrome (SBS) in subjects who are dependent upon parenteral nutrition (PN).  PN is the practice of feeding a patient intravenously, the cost of which can exceed $100,000 a year.

SBS is a disabling syndrome that can arise after a resection of the small bowel. There are an estimated 10,000 to 15,000 SBS patients in North America who are PN-dependent.

Gattex was granted Orphan Drug status in the U.S. for SBS in August 2000.

This extension study enrolled 65 of the 71 subjects who had completed a 24-week randomized phase III study that evaluated low dose Gattex (0.05 mg/kg/day) and high-dose Gattex (0.10 mg/kg/day) versus placebo. The primary objective of the study was to assess the long-term safety and tolerability of daily Gattex dosing for up to 52 weeks.

Sixty-eight percent of the subjects who had received low-dose Gattex therapy and continued on low-dose Gattex, and 52% of the subjects who had received high-dose Gattex therapy and continued on high-dose Gattex achieved a 20% or greater reduction in PN after a total of 52 weeks of therapy.

Subjects treated with low-dose Gattex showed a mean 51% reduction in PN volume from pretreatment baseline to the end of 52 weeks (p< 0.001) and those treated with high-dose Gattex experienced a mean 24% reduction (p< 0.001).All of the subjects (100%) who had previously received placebo in the phase III study and were randomized to low-dose

Gattex therapy, and two out of seven subjects who had previously received placebo in the phase III study and were randomized to high-dose Gattex therapy, achieved a 20% or greater reduction in PN after a total of 28 weeks of therapy in the extension study.

Treatment was well tolerated in both dose groups with no statistical differences in the rate of adverse events compared with the placebo group.

Based on a series of positive phase III results, NPS is currently meeting with the FDA to discuss the path towards regulatory approval.

Tracy Trundle is a Research Analyst at CenterWatch.

RLS Drug Shows Promise in Pivotal Trial

XenoPort and GlaxoSmithKline reported positive top-line results from a phase III trial of XP13512, a gabapentin pro-drug with enhanced absorption, for the treatment of moderate to severe restless legs syndrome. This 12-week, double-blind, placebo-controlled study, dubbed XP053, enrolled 325 subjects. The endpoints were met with statistical significance in both dose groups when compared to placebo.

The subjects received placebo or 600 mg or1, 200 mg of XP13512, given once per day. The primary endpoints were the change from baseline for the International Restless Legs Syndrome (IRLS) rating scale score at end of treatment and the percentage of subjects showing significant improvement on the Investigator Clinical Global Impression of Improvement (CGI-I) scale at end of treatment.

In the 600 mg dose group, the unadjusted mean reduction in the IRLS scale score was -13.8 (p less than 0.0001). 

At the end of treatment, 73% of subjects treated with 600 mg of XP13512 were reported as “much improved” or “very much improved” on the CGI-I scale (p less than 0.0001 compared with placebo). In the 1,200 mg dose group, the unadjusted mean reduction in the IRLS scale score was -13.0 versus -9.8 for placebo (p=0.0015).

At the end of treatment, 78% of subjects treated with 1,200 mg XP13512 were reported as “much improved” or “very much improved” on the CGI-I scale compared with 45% treated with placebo (p less than 0.0001). Treatment was generally well tolerated, with adverse events mild to moderate.

An New Drug Application (NDA) filing is planned for the third quarter of this year.

In February 2007, GlaxoSmithKline and XenoPort entered into an exclusive development and commercialization collaboration for the drug.

EDICT Project Opens Policy Recommendations For Public Comment

The EDICT project, short for Eliminating Disparities in Clinical Trials, has invited the public to comment on a series of policy proposals design to help patient recruitment and retention in clinical trials. The period open to public comment runs until March 21.

Shortly after, the final policy recommendations will be brought before the Congress, the National Institutes of Health and the Food and Drug Administration.

Among the issues the policies address are minority participation, patient insurance, informed consent, and standards and accreditation. EDICT is a collaborative alliance between Baylor College of Medicine’s Chronic Disease Prevention and Control Research Center and the Intercultural Cancer Council (ICI). It consists of researchers, public health officials, patient advocates and other various stakeholders.

The four-year project is supported by an unrestricted grant from Genentech.

GVAX Show Antibody Respone in Prostate Cancer

Cell Genesys reported positive results from a phase II trial of GVAX for the treatment of prostate cancer. GVAX is a cell vaccine that is also being evaluated for the treatment of leukemia and pancreatic cancer.  The autologous vaccine is made by removing a sample of the patient's own tumor and coaxing it into producing granulocyte-macrophage colony stimulating factor (GM-CSF). The vaccine is then re-administered into the patient via injection, which initiates a potent immune response against the tumor.

The trial analysis was designed to evaluate the potential association between immune responses to GVAX and increased survival. The study enrolled 80 subjects, including 65 who had their serum evaluated to determine each subjects' immune response to two specific antigens, HLA-A24 and FLJ14668, following GVAX treatment. Of the 65 subjects, 34 demonstrated FLJ14668-specific antibody immune response and had a median survival of 43 months. 

The median survival of subjects who did not generate the anti-FLJ14668 antibodies was 21 months (p=0.002). Twenty-two of the 65 subjects received a dose of GVAX comparable to that being evaluated in ongoing phase III prostate cancer trials. Of the 22 subjects, 16 (73%) mounted an immune response to FLJ14668.

These 16 subjects achieved a median survival of 44.9 months. The median survival for all 22 subjects in this treatment group was 35 months. Of the 58 subjects who were HLA-A24 genotype negative and therefore potentially able to mount anti-HLA-A24 specific antibody responses, 30 subjects were found to be anti-HLA-A24 antibody positive. These 30 had a median survival of 43 months, compared with a median survival of 18 months in the subjects who did not generate anti-HLA-A24 antibodies (p=0.05).

"The findings being reported today indicate a potential association between two specific GVAX-induced antibody responses and patient survival, an association consistent with the proposed mechanism of action for this product. We look forward to expanding these findings in a prospective analysis of the sera of patients treated in our two randomized controlled phase III trials," stated Peter Working, Ph.D., senior vice president of research and development at Cell Genesys.

The results will be presented by Thomas Harding, Ph.D, and colleagues from Cell Genesys at the American Society of Clinical Oncology's Genitourinary Cancer Symposium held in San Francisco. Phase III trials are currently underway.

Trial Results for Psoriasis Drug Ustekinumab Hit Mark

Centocor reported one year data from a phase III trial of ustekinumab (CNTO-1275), a monoclonal antibody against the p40 subunit of IL-12 and IL-23 for the treatment of moderate to severe plaque psoriasis. This randomized, double-blind, placebo-controlled trial, dubbed PHOENIX-1, enrolled 766 subjects.

The subjects received subcutaneously administered ustekinumab (45 mg or 90 mg) at Weeks 0 and 4 followed by the same dose every 12 weeks, or placebo. Following the double blind phase, the subjects in the placebo group crossed over to receive either 45 mg or 90 mg doses of ustekinumab at Weeks 12 and 16 and every 12 weeks thereafter.

The primary endpoint was the proportion of subjects achieving at least a 75% improvement on the Psoriasis Area and Severity Index (PASI 75) at Week 12. The endpoint was reached; after two doses of ustekinumab 67% of subjects receiving the 45 mg dose and 66% of subjects receiving the 90 mg dose achieved PASI 75 compared with 3% of subjects receiving placebo (p<0.001).

In addition, 42% of subjects in the 45 mg ustekinumab dosing group and 37% of subjects in the 90 mg ustekinumab dosing group achieved PASI 90, compared with 2% of subjects receiving placebo (p<0.001). The subjects who received 45 mg or 90 mg of ustekinumab and consistently achieved a 75% improvement from baseline were randomized at Week 40 to either continue treatment or switch to placebo, with levels of response to maintenance therapy measured at Week 52.

Of those subjects who continued treatment with ustekinumab 45 mg and 90 mg, 87% and 91%, respectively, had a sustained PASI 75 response compared with 64% and 62% of subjects switched to placebo (p less than or equal to 0.001 for 45 mg comparison; <0.001 for 90 mg comparison).

Also at Week 40, 66% and 73% of subjects achieved PASI 90 after receiving either 45 mg ustekinumab or 90 mg ustekinumab, respectively, and response rates remained stable through Week 52 with continued treatment, compared with 37% and 38% of subjects switched to placebo. The adverse events profile was comparable between the treatment arms.

Johnson & Johnson subsidiary Centocor and Janssen-Cilag are developing ustekinumab. A Biologic License Application (BLA) is currently under review by the U.S. Food and Drug Administration (FDA).

Veritas Medicine Restructures Business, Drops Trial Listing Service

By Stephen DeSantis

Cambridge, Mass.-based Veritas Medicine, a clinical trial services company, has discontinued its patient recruitment services and laid off a number of employees.

According to Veritas, it is restructuring the company to focus solely on its clinical trial disclosure business. The company’s clinical trial listing service and patient screening business will be terminated.

Veritas stated it ceased providing patient recruitment services on Feb. 8.

The company’s clinical trial listings service had been a major part of its business since its inception. One of its main patient recruitment services asked for potential subjects looking to enroll in trials to fill out medical and geographic information, which could then be matched with studies posted by sponsors. That service also contained a trial notification message to be sent to potential subjects via email.

“There have been reductions of staff who were directly related to the patient recruitment business, but the clinical data disclosure team is intact,” said Andrew O’Brien, Veritas’ president and chief executive officer, in a statement to CWWeekly.

The company is responding to the evolving landscape of the industry’s transparency requirements. That business consists of Veritas’ clinical trial registry system, its sponsor registry web site development and its patient response service.

“Historically, this has been a smaller part of our business, but it certainly is where we see the best growth prospects today,” said O’Brien.

The company’s web-based platform allows clients to post trial listings and results to different registries. Veritas’ web site development service helps its clients develop their own corporate registry sites in a branded environment.

“We’re focusing Veritas Medicine on the clinical data disclosure business because there is a terrific market opportunity and we are very well positioned there...the disclosure requirements for our biopharmaceutical customers are growing more complex,” said O’Brien.

In the last year, Veritas has been through some significant changes. After seven years as Veritas’ chief executive officer, Joe Avellone, M.D., left. In May 2007, Parexel, a Waltham, Mass.-based contract research organization, named Avellone to the position of corporate vice president of clinical research operations for both North and Latin America. Avellone remains on the company’s board of directors. He previously served as chief operating officer for BlueCross BlueShield of Massachusetts.

Veritas was founded in 1999 with an initial investment of $8 million from Burrill & Company, BioAsia’s Biotechnology Development Fund II, Cambridge Incubator and Seaflower Ventures. Three years after launch, Veritas had raised a total of $16 million in funding. Its current list of investors includes Burrill & Company, Vivo Cambridge Innovations, Seaflower Ventures and MDS Capital.

Stephen DeSantis is the Senior Associate Editor at CenterWatch.

Rituximab Hits Endpoints for New Indication

Roche issued positive results from a phase III trial of MabThera (Rituxan, rituximab) as a first-line therapy for rheumatoid arthritis. This international, randomized, placebo controlled, double blind, parallel group study was dubbed SERENE (Study Evaluating Rituximab’s Efficacy in methotrexate iNadequate rEsponders).

The trial enrolled five hundred and nine subjects who received either MabThera (500 mg or 1000 mg) or placebo by intravenous infusion on days one and fifteen, plus weekly methotrexate (MTX).

The primary endpoint was the percentage of subjects who had at least a 20% reduction in a number of symptoms and measures of disease, measured via the American College of Rheumatology assessment (ACR20) at week twenty four.  The primary endpoint was reached; a significantly greater proportion of subjects treated with MabThera/MTX achieved an improvement in disease signs and symptoms compared to those treated with MTX alone. Treatment was well tolerated, with a profile consistent with previous studies.

“These data support the potential for MabThera to be used earlier in the course of treatment for RA. The results are encouraging and show that MabThera represents a promising alternative to current treatment options in patients who have an inadequate response to traditional therapy”, said William Burns, chief executive officer of Roche's pharmaceuticals division.

Rituximab is already approved rheumatoid arthritis in combination with methotrexate. It is also approved certain forms of B-cell non-Hodgkin's lymphoma (NHL).

Based on the results, Roche intends to file for FDA approval of MabThera as a first-line therapy.

Rituximab is a (mouse/human chimeric) anti-CD20 monoclonal antibody developed and launched by IDEC Pharmaceuticals (now Biogen Idec), Genentech, Roche Holding and Zenyaku Kogyo.

Type I Diabetes Drug See Positive Results in Phase II

By Tracy Trundle

Diamyd Medical (formerly issued positive long-term results from a phase IIb trial of Diamyd, GAD-65), recombinant glutamic acid decarboxylase (GAD) delivered with alum for injection, for the treatment of type I diabetes. This randomized study enrolled seventy pediatric and adolescent subjects in Sweden.

The subjects received two single injections of Diamyd or placebo. The primary endpoint for the trial was the preservation of beta cell function as measured by C-peptide.

Thirty months after the first injection, preservation of insulin was significantly higher in subjects receiving Diamyd, both in the fasting state and after meal stimulation, compared with placebo-treated subjects.

Diamyd also increased GAD antibody levels at fifteen and twenty one months post-injection. Based on the data, phase III trials are planned.

The GAD gene technology was originally developed by the University of California, Los Angeles (UCLA). In 1997, BioSyn was granted an exclusive worldwide license to UCLA's GAD technology.

Tracy Trundle is a Research Analyst at CenterWatch.

Negative or Positive Trial Results?

By Steve Zisson

There’s some great quotes in the Wall Street Journal’s story about the New England Journal of Medicine’s assertion that effectiveness of antidepressants has been exaggerated by selective publication of positive clinical trial results.

The NEJM study reviewed unpublished trial data submitted to the U.S. Food and Drug Administration (FDA).

The NEJM research was led by Erick Turner, a psychiatrist at Oregon Health and Science University. Turner previously worked at the FDA where he reviewed psychotropic drugs.

Here’s the best quote in the article from Turner about what he believes are doctor’s attitudes toward prescribing antidepressants.

"There is a view that these drugs are effective all the time," he said. "I would say they only work 40% to 50% of the time," based on his reviews of the research at the FDA, "and they would say, 'What are you talking about? I have never seen a negative study.'"

Who’s view? Do doctors believe that these antidepressants, or any drugs, work 100% of the time? Isn’t 40% to 50% effectiveness considered a successful drug?

You can check out the WSJ story here.

Steve Zisson is editorial director of CenterWatch.

Non-Hodgkin's Lymphoma Drug Misses Primary Endpoint

By Tracy Trundle

Genitope reported negative results from a phase III trial of MyVax, a patient-specific immunotherapy, for the treatment of previously untreated follicular B-cell non-Hodgkin’s lymphoma (fNHL). The subjects enrolled in this double-blind, randomized, controlled clinical trial first received chemotherapy to reduce their tumor burden, followed by a six-month rest period.

Subjects who maintained at least a partial response through the rest period were then randomized to the MyVax personalized immunotherapy or control arm in a 2:1 ratio. Subjects who received MyVax personalized immunotherapy received a patient and tumor-specific idiotype protein conjugated to a foreign carrier protein called keyhole- limpet hemocyanin (KLH). Subjects in the control arm received a non-specific immunotherapy consisting only of KLH.

Subjects in both arms received granulocyte macrophage-colony stimulating factor (GMCSF) as an immunologic adjuvant at each immunization. Although treatment was determined to be safe and well tolerated, the trial did not meet its primary endpoint. In the primary analysis, there was no statistically significant difference in the progression-free survival (PFS) of subjects receiving MyVax compared to the control arm.

Analysis of a pre-specified endpoint in the MyVax arm showed a highly statistically significant difference in PFS between subjects who mounted a positive immune response to the tumor-specific target and those who did not.

Based on the results, Genitope plans to meet with the U.S. Food and Drug Administration (FDA) to determine the path forward for MyVax personalized immunotherapy. The FDA granted the drug Fast Track status in 2006.

Tracy Trundle is a Research Analyst at CenterWatch.

Gout Drug Shows Promise in Two Pivotal Trials

By Tracy Trundle

Savient Pharmaceuticals reported positive results from two phase III trials, GOUT 1 [Gout Outcomes and Uric acid Treatment] and GOUT 2, of Puricase, a pegylated recombinant urate oxidase for the treatment of gout. The disease is caused by the deposit of urate crystals (via uric acid) in the body's tissues such as joints, tendons and organs. Most traditional treatments have centered on blocking the production of uric acid in the body, whereas Puricase attempts to reduce the levels of uric acid in the blood stream.

Puricase (8 mg) administered by a two hour intravenous infusion every two weeks or every four weeks met the primary efficacy endpoint in the intent-to-treat (ITT) and per protocol analyses.

The primary endpoint was normalization of plasma uric acid during months 3 and 6 of the clinical trials. In the ITT analysis the mean responder rate for the every two-week dose group pooled across both studies was 42% (p is less than 0.001) and the mean responder rate for the every four-week dose group was 35% (p is less than 0.001).

In the per protocol analysis the responder rate for the every two weeks dose group was 61% (p is less than 0.001), and every four weeks was 50% (p is less than 0.001). The placebo responder rate for placebo was zero in both the ITT and Per Protocol analyses. A key secondary endpoint was reduction of gout tophi (grouped crystal deposits).

The every two week dose arm attained statistical significance in the pre-specified pooled analysis (p equal to 0.005) for the elimination of gout tophi. The every four week dose group did not attain statistical significance. Treatment was generally well tolerated.

Based on these results, Savient plans to file a (Biologic Li cease Application) BLA with the U.S. Food and Drug Administration (FDA) in 2008. Puricase was licensed from Duke University in 1998. According to the Centers for Disease Control (CDC), Gout may affect as much as 2.7% of the U.S. population alone.

Tracy Trundle is a Research Analyst at CenterWatch.

Platelet Growth Factor Hits Endpoints in Phase II

By Tracy Trundle

GlaxoSmithKline reported positive results from two phase II trials of Promacta -- a non-peptide thrombopoietin receptor agonist (platelet growth factor) which can stimulate the growth and differentiation of bone marrow cells that priduce blood platelets -- for the treatment of chronic hepatitis C-associated thrombocytopenia and chronic Idiopathic thrombocytopenic purpura (ITP). The first study was an international, multicenter, double-blind, randomized, placebo-controlled, dose-ranging study. A total of seventy-four HCV-infected subjects with platelet counts between 20,000 and 70,000/mL were enrolled. The subjects received Promacta (30mg, 50mg, or 75mg daily) or placebo for four weeks (pre-antiviral phase).

The primary endpoint was platelet count increase to greater than or equal to 100,000/mL at week four. The subjects could then initiate antiviral therapy and continue Promacta or placebo for 12 additional weeks (antiviral phase).

The primary endpoint was reached by 75%, 79% and 95% of subjects in the Promacta 30mg, 50mg and 75 mg groups respectively, compared to no platelet elevations in the placebo group (p<0.001). Treatment was generally well tolerated, with all adverse events mild to moderate in nature. The second trial was a multicenter, randomized, double-blind, placebo-controlled study.

A total of 118 subjects with chronic ITP and platelet counts <30,000/mL and who had relapsed or were refractory to at least one ITP treatment were enrolled. The subjects received once-daily oral Promacta (30mg, 50mg, or 75 mg) or placebo. The primary endpoint was the proportion of subjects with a platelet count greater than or equal to 50,000 per cubic millimeter after up to six weeks of therapy.

The primary endpoint was achieved in 28%, 70% and 81% of subjects who received Promacta (30mg, 50mg and 75mg, respectively) compared to 11% of the  placebo group <0.001). Platelet counts rose to greater than 200,000/µL in 4% of the placebo-treated subjects and in 14%, 37% and 50% of the Promacta 30mg, 50mg and 75mg-treated subjects, respectively. Treatment was generally well tolerated.

Phase III trials of Promacta are currently underway.   

Tracy Trundle is a Research Analyst at CenterWatch.

Drug for Excessive Sleepiness Shows Promise in Phase II Study

By Tracy Trundle

Vanda Pharmaceuticals reported positive results from a phase II trial of VSF-173, an orally administered stimulant, for the treatment of excessive sleepiness. This randomized, double-blind, placebo-controlled trial enrolled  fifty-five subjects who received three doses of VSF-173 administered at 50 mg, 100 mg and 200 mg and placebo administered at 25 mg, 50 mg and 100 mg at the usual bedtime and at four hours after the first dose.

Efficacy was measured via a series of six Maintenance of Wakefulness Tests (MWT) given two hours apart starting one hour after the first dose, as well as the scheduled daytime recovery sleep following the night time and morning evaluations. Although not statistically significant, VSF-173 demonstrated improvement over placebo on the primary endpoint, the effect of the compound on the first four series of MWT tests.

The mean MWT sleep onset scores for the 50 mg, 100 mg and 200 mg, and placebo groups were 10.3, 12.9, 10.6 and 9.2 minutes, respectively. In a subset of 37 subjects with no observed impairment in pre-dose daytime wakefulness, the mean of all six MWT scores for the 50 mg, 100 mg and 200 mg groups showed improvements of 2.1, 3.4 and 2.1 minutes, respectively, compared to placebo. For the dose group of 100 mg, this observation of improvement was statistically significant (p < 0.05).

During the scheduled daytime recovery sleep, statistically significant, dose-dependent correlations were observed with the following polysomnography (PSG) parameters: increased number of awakenings, decreased sleep efficiency and total sleep time for the first third of the sleep period, and increased wake time after sleep onset for the first 3 hours of the sleep period (p<.05).

Vanda licensed VSF-173 from Novartis Pharma AG. Based on the results, Vanda plans to move forward with the development of the drug.

Tracy Trundle is a Research Analyst at CenterWatch.

Centocor Psoriasis Drug Shows Impressive Results

By Tracy Trundle

Johnson & Johnson’s Centocor reported positive results from a phase III trial of CNTO1275 (ustekinumab) for the treatment of psoriasis. CNTO1275 is a monoclonal antibody (mAb) against the p40 subunit of interleukin 12 (IL-12) and IL-23. This randomized, double-blind, placebo-controlled study, dubbed PHOENIX 2, enrolled 1,230 subjects with chronic psoriasis.

The subjects received CNTO1275 administered subcutaneously or placebo. In the CNTO1275 arm, the subjects received 45 mg or 90 mg doses at weeks 0 and 4 followed by the same dose every twelve weeks. Those in the placebo arm crossed over to receive either 45 mg or 90 mg doses of CNTO1275 at weeks 12 and 16 and every subsequent twelve weeks.

The primary endpoint was the proportion of subjects who achieved a Psoriasis Area and Severity Index (PASI) score of 75 at Week 12.

By Week 12, 67% of the subjects treated with 45 mg of CNTO1275 and 76% of those treated with 90 mg of CNTO1275 achieved PASI75 compared with 4% of those treated with placebo (p < 0.001). In addition, 42% of the subjects in the 45 mg arm and 51% in the 90mg arm achieved a PASI 90, or almost complete clearance of psoriasis, compared with 1% in the placebo arm (p < 0.001).

Comparable results were seen in the placebo group twelve weeks after crossover to CNTO1275. Following an additional dose at Week 16, responses were maintained through Week 28.

Treatment was well tolerated, with adverse events comparable between the CNTO1275 and placebo groups.

Psoriasis is an immune-mediated, genetic disease affecting the skin and the joints. According to the National Institutes of Health (NIH), an estimated 125 million people worldwide have psoriasis.

Tracy Trundle is a Research Analyst at CenterWatch.

Gene Therapy Drug Shows Promise in MS Patients

By Tracy Trundle

Palo Alto, Calif.-based Bayhill Therapeutics reported positive results from a phase IIb trial of BHT-3009 for the treatment of multiple sclerosis. BHT-3009 is a gene therapy drug that delivers DNA that instructs cells to produce myelin basic protein (MBP). Myelin is the phospholipid sheath that surrounds neurons and is the target of many autoimmune diseases such as MS.

This multi-center, randomized, double-blind, placebo-controlled study enrolled 289 subjects with relapsing, remitting multiple sclerosis. The subjects received monthly intramuscular injections of BHT-3009 for one year.

The primary endpoints were brain magnetic resonance imaging (MRI) measures of disease activity including gadolinium-enhancing lesions, T2 lesions and T1 black holes. Subjects in a prospectively defined group with high anti-myelin basic protein (MBP) antibodies in their cerebral spinal fluid (CSF) showed statistically significantly fewer gadolinium-enhancing lesions in their brain after treatment with 0.5 mg BHT-3009 compared to placebo.

Reductions in T2 lesions and T1 black holed were also observed in this population. In addition, significant reductions in several CSF myelin-specific autoantibodies were achieved in all the subjects treated with 0.5 mg BHT-3009 compared to placebo.

Based on the results, Bayhill plans to meet with the FDA to discuss a phase III trial design.

According to the National Multiple Sclerosis Society, MS is believed to afflict 400,000 Americans and 2.5 million people worldwide.

Tracy Trundle is a Research Analyst at CenterWatch.

Promising Results Seen in Lung Cancer Trials

By Tracy Trundle

Merck KGaA reported positive long-term results from a phase II trial of Stimuvax for the treatment of non-small cell lung cancer (NSCLC). The drug is a MUC-1 peptide-based liposomal vaccine, for the potential  treatment of cancers.

This study enrolled 171 subjects with stage IIIB/IV with stable or responding disease after any first-line chemotherapy with or without radiotherapy. The subjects were stratified by disease stage then randomized to receive Stimuvax plus best supportive care (BSC) or BSC alone.

The subjects in the Stimuvax arm received a single intravenous dose of cyclophosphamide 300mg/m2 followed by eight weekly subcutaneous immunizations with Stimuvax (1,000 mg).Although the overall study results did not reach statistical significance, the subjects with stage IIIB cancer receiving Stimuvax showed a median survival of 30.6 months compared with 13.3 months in the control group. At the three year follow-up, 49% of subjects who were treated with Stimuvax were still alive compared with 27% treated with BSC alone, representing a 45% reduction in mortality.

Based on the results, Merck KGaA is currently conducting a phase III trial of Stimuvax for the treatment of stage IIIA or IIIB NSCLC. Merck KGaA and Edmonton-based biotech Biomira entered into a development and commercialization licensing agreement for Stimuvax.

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Also Pfizer released positive preliminary results from a phase II trial of sunitinib (Sutent), a multi-kinase inhibitor for the treatment of NSCLC. Sunitinib is already approved for the treatment of gastrointestinal tumors and renal cell carcinoma.

The trial was designed to compare sunitinib (37.5 mg/day) in combination with erlotinib (150 mg/day) in previously treated subjects with advanced NSCLC. The primary endpoint was safety and tolerability. Secondary endpoints included anti-tumor activity. The combination treatment was generally safe and well tolerated, with all adverse events mild to moderate in nature.

Two subjects had partial response; one which was maintained for more than three months and one which was currently ongoing. In addition, stable disease up to or more than 16 weeks was observed in two subjects. The randomized portion of this trial is currently underway.

Tracey Trundle is a Research Analyst at CenterWatch.

ARISE Trials Shows Promising Results for Diabetes

By Tracy Trundle

Atherogenics reported positive results from a phase III trial of succinobucol (AGI-1067), an antioxidant oral vascular cell adhesion molecule-1 (VCAM-1) gene expression inhibitor, for the treatment of diabetes and coronary heart disease. This trial, dubbed ARISE (Aggressive Reduction of Inflammation Stops Events), enrolled over 6,000 subjects internationally. Results were reported at the European Society of Cardiology Congress 2007.

Subjects received AGI-1067 or placebo both in conjunction with standard of care. After 12 months of treatment, AGI-1067 significantly lowered levels of glycated hemoglobin A1c, a measure of glycemic control, in subjects with and without diabetes. In addition, the data showed a 59% reduction in the development of new onset diabetes in subjects with impaired fasting glucose (p < 0.0001). ).

In the subjects with diabetes, AGI-1067 showed a 22% reduction in hard cardiovascular events of cardiovascular death, cardiac arrest, myocardial infarction and stroke (p=0.062). Additional phase III trials are currently underway.

In December 2005, AstraZeneca and AtheroGenics signed a $1 billion deal to co-developement and marketwith AGI-1067. However, in April 2007, AstraZeneca terminated the agreement due to initial negative preminary results of the ARISE study for the treatment of heart disease. After initialing failing to meet specific endpoints in the ARISE study for the treatment of heart disease, Atherogeneics stated in May, that the company plans to continue to develop the product for diabetes.

Heart Drug Combo Reduces "Flushing"

By Tracy Trundle

Merck reported positive results from a phase III trial of Cordaptive for the treatment of dyslipidemia. Cordaptive was shown to lower LDL --or bad -- cholesterol and raise HDL -- or good -- cholesterol, while lowering some of the side effects of such drugs.

The drug is a combination of extended-release niacin and an investigative compound called laropiprant (MK-0524). laropiprant is an inhibitor of niacin-induced flushing, a common side effect of some cholesterol drugs. The combo is being investigated for the prevention of coronary heart disease (CHD, coronary artery disease) and atherosclerosis.

The double-blind, randomized trial enrolled 1,613 subjects who received Cordaptive (1 gram/day), extended-release niacin alone (1 gram/day) or placebo. After four weeks, the active treatment groups doubled their respective doses to 2 grams per day for an additional 20 weeks.

The co-primary endpoints were the effects of 2 grams of Cordaptive versus placebo on percent changes in LDL-cholesterol (LDL-C) across weeks 12 to 24, and the effects of 1 gram of Cordaptive versus extended-release niacin on flushing symptom severity during the first week of treatment. In the subjects who advanced to 2 grams of Cordaptive, LDL-C levels were reduced from baseline by an average of 19% (versus a reduction of 0.5% with placebo). In addition, in the subjects receiving 1 mg of Cordaptive, 69% reported either no flushing symptoms or mild flushing symptoms during the first week of treatment compared to 44% of those who received extended-release niacin alone.

Secondary endpoints included the effects of 2 grams of Cordaptive versus placebo on HDL-cholesterol (HDL- C) levels, triglyceride levels and other lipid parameters, and the flushing frequency and intensity of 2 grams of Cordaptive compared to extended-release niacin alone.  In the subjects receiving Cordaptive 2 mg their HDL-C levels increased by an average of 19% (versus a reduction of 1.2% with placebo), and their triglyceride levels were reduced by an average of 22% (versus an increase of 3.6% with placebo). By week 24, the frequency of moderate or greater flushing was 2 days/week for subjects receiving 2 grams of Cordaptive or a placebo versus 7 days/week among those treated with 2 grams of extended-release niacin.

A New Drug Application (NDA) for Cordaptive for the treatment of dyslipidemia is currently under review by the FDA. A decision is expected by mid 2008.

Cardium's Heart Drug Shows Mixed Results

By Tracy Trundle

Cardium reported mixed results from two phase IIb/III trials of Generx (alferminogene tadenovec, Ad5FGF-4) for the treatment of chronic angina. These randomized, double-blind, placebo-controlled trials were dubbed AGENT (Angiogenic GENe Therapy -3 and -4 and enrolled a total of 532 subjects in the US and Europe.  Subjects received a low dose or high dose of Generx, administered via intracoronary infusion or placebo for 12 weeks. The primary endpoint was the change from baseline in exercise treadmill time (ETT) at 12 weeks and at secondary time points of 4 weeks and 6 months. Secondary endpoints included time to 1 mm ST-segment depression, time to onset of angina and change in Canadian Cardiovascular Society (CCS) class. Pooled data showed no significant difference in the active groups versus placebo in the primary endpoint.

There was a large and significant placebo effect compared with baseline, which persisted over 6 months. In addition, none of the secondary endpoints were achieved with the exception of change in CSS class; significant improvement over placebo only for the high-dose group was observed at week 12, month 6, and month 12 (p< 0.05).

However, in a pooled analysis of pre-specified subgroups statistically significant results were seen among women in all the primary and secondary endpoints as compared to placebo. These were observed at both the three and six month evaluation endpoints for the high dose group (p less than 0.01 to p less than 0.05). In addition, treatment with the low dose of Generx showed statistically significant results over placebo in ETT at three and six months, time to ST-segment depression at six months, and CCS Class at twelve months (p less than 0.05).

Based on the results, Cardium created an FDA approved adjusted clinical protocol and is currently conducting a phase III study in women with angina. 

Cymbalta Reduces Pain in Fibromyalgia Trial

Eli Lilly reported positive results from a phase III trial of Cymbalta (duloxetine) for the treatment of fibromyalgia. Cymbalta is Lilly’s serotonin and norepinephrine reuptake inhibitor (SSNRI), approved in the U.S. for major depression and diabetic (peripheral neuropathic) pain. Merrill Lynch has forecasted the product could reach worldwide sales of $2.2 billion in 2008.

This randomized, placebo-controlled trial enrolled subjects with fibromyalgia, with or without depression, who received Cymbalta (60 mg or 120 mg) or placebo. They were subsequently measured at three and six months for improvements on the Brief Pain Inventory Average Pain Score (BPI) and the Patient's Global Impression of Improvement questionnaire (PGI- I). At three months, subjects in both Cymbalta arms showed significantly greater reduction in pain and improvement in PGI-I scores compared with the placebo group.

In addition, more subjects treated with Cymbalta (both 60mg and 120 mg) showed significantly greater reduction in pain as measured by a 30% improvement in baseline BPI scores (50.7% and 52.1%, respectively), compared with those taking placebo (36%).

At the end of the six-month trial, more subjects treated with both doses of Cymbalta showed a response to treatment, defined as a 50% reduction of baseline BPI scores, (32.6% and 35.9%, respectively), compared with subjects taking placebo (21.6%).

A supplemental new drug application (sNDA) for the treatment of fibromyalgia is currently under review by the FDA.

Fibromyalgia syndrome is a chronic, but sometimes debilitating, musculoskeletal pain and fatigue disorder. The disorder affects about 3 - 6 million people in the U.S. each year. Its cause is not known.

Lupus Drug Shows Promise in Phase I/II Trial

By Tracy Trundle

UCB and Immunomedics reported positive results from a follow-up phase I/II trial of epratuzumab for the treatment of systemic lupus erythematosus (SLE). Phase I of the trial enrolled 12 subjects with SLE and analyzed the effect of epratuzumab on circulatory B-cell subsets. Results showed that epratuzumab preferentially targets naive and transitional B-cells.

Phase II of the trial enrolled 11 subjects with SLE and 7 subjects without SLE. It was designed to analyze the effect of epratuzumab on the inhibition of the activation of B-cells. Epratuzumab stopped the over-activation of B-cells from SLE subjects but not normal B-cells, when activated by certain immune stimulating agents. Based on the results, Immunomedics plans to move forward with the development of epratuzumab. In May 2006, Immunomedics co-licensed exclusive rights to epratuzumab for all autoimmune indications to UCB.

Lupus is an autoimmune disease that causes the body's immune system to attack its own tissues, causing serious inflammation and pain. The Lupus Foundation of America (LFA) estimates that between 1.5 and 2 million people in the U.S. have the disease.

China and India Join WHO Registry Database

China and India have joined a World Health Organization (WHO)-run international database of clinical trials. Both countries had already recently established their own databases but had to align those registries with a set of standard criteria set forth by a team of experts at the United Nations.

The database was established following an international summit on transparency in Mexico City in November 2004.

“Access to information about ongoing, completed and published clinical trials is essential for informed decision-making. Researchers, research funders, policy-makers, medical practitioners, patients and the general public need such information, to help guide research or to make treatment decisions,” stated the International Clinical Trials Registry Platform (ICTRP) web site.

The WHO is currently evaluating at least eight additional registries, including those from South Africa and Hong Kong. According to published reports, Germany and Brazil are also attempting to join the group. The U.S. is already submitting trials from its registry, clinicaltrials.gov.

The WHO clinical trials registry site can be found here. (http://www.who.int/trialsearch)

NovaCardia Sees Positive Results with treatment for heart failure

By Tracy Trundle

NovaCardia reported positive preliminary results from a phase III trial of KW-3902 for the treatment of acute congestive heart failure (CHF). This double-blind, randomized trial enrolled 304 subjects with CHF and renal impairment. Subjects received placebo or 10, 20 or 30 milligram doses of intravenous KW- 3902, administered daily for up to three days. All subjects received intravenous furosemide.

The primary endpoint was the proportion of subjects in the categories of treatment success, treatment failure or no change. The 30 mg dose of KW-3902 appeared to be the most efficacious, with higher rates of treatment success and lower rates of treatment failure compared to placebo.

Twenty-four hours post-treatment, self-reported marked or moderate improvement in dyspnea was reported in 66% of the KW-3902 (30 mg) group compared to 51% of the placebo group. No statistically significant differences in adverse events were reported between the groups. The 30 mg dose of KW-3902 was determined to be the optimal dose for NovaCardia’s two 600-subject phase III trials, dubbed PROTECT-1 and PROTECT-2.

Both trials are enrolling subjects in the U.S., Canada, Europe, Israel and Russia.

Tracy Trundle is a Research Analyst at Thomson CenterWatch.

Novartis And Vanda See Positive Results With iloperidone

By Tracy Trundle

Novartis and Vanda Pharmaceuticals reported positive results from a phase III trial of iloperidone for the treatment of akathisia in schizophrenia. This randomized, double-blind, placebo controlled trial enrolled 706 subjects who were placed into one of four treatment groups: iloperidone 12.16 mg/d or 20.24 mg/d, risperidone 6.8 mg/d or placebo for 6 weeks. Changes in akathisia were measured weekly by the Barnes Akathisia Scale (BAS) and the Extrapyramidal Symptom Rating Scale (ESRS) from baseline to the six-week end point.

Both iloperidone groups had fewer subjects whose total akathisia score worsened (12%, p=0.04; 8%, p=0.004, respectively), compared to placebo and risperidone (20%, p=1.00). In addition, anticholinergic medication was needed for extrapyramidal symptoms in 5% and 7% of the two iloperidone dose groups respectively, compared with 22% for risperidone and 7% for placebo. The results were presented at the 2007 American Psychiatric Association annual meeting.

Vanda licensed iloperidone in 2004 from Novartis Pharma AG and is completing the phase III program. Based on the results, the Vanda  expect to file a NDA in Q4 of 2007.