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Pharmaceutical and Biotech News


April 11, 2011

Biogen Idec Multiple Sclerosis Drug, BG-12 (dimethyl fumarate) Achieves Endpoints in Placebo-Controlled Phase 3 Study


Biogen Idec announced top-line results from DEFINE, the first of two pivotal Phase 3 clinical trials designed to evaluate the investigational oral compound BG-12 (dimethyl fumarate) as a monotherapy in people with relapsing-remitting multiple sclerosis (RRMS). BG-12 is a methyl ester of fumaric acid and has been used in the treatment of psoriasis. During the investigation of the properties of this molecule, it was found to have immunomodulatory and neuroprotective effects.  A phase 2 study in multiple sclerosis did show that patients treated with BG-12 developed significantly fewer brain lesions than the controls after a period of 24 weeks.

The DEFINE (Determination of the Efficacy and safety of oral Fumarate IN rElapsing-remitting MS) clinical study was pivotal (Phase 3) randomized, double-blind, placebo-controlled, dose-ranging study to determine the efficacy and safety of BG-12 in approximately 1,200 people with RRMS. The study evaluated two doses of BG-12: 240 mg twice a day and 240 mg three times a day. The primary objective was to determine if BG-12 is effective in reducing the proportion of relapsing patients at two years. Secondary endpoints included (a) reduction in the number of new or newly enlarging lesions as measured by MRI; (b)reduction in annualized relapse rate; (c) reduction of disability progression as measured by the Expanded Disability Status Scale (EDSS); and (d) the safety and tolerability of BG-12.

Results showed that 240 mg of BG-12, administered either twice or three times a day, met the primary study endpoint, demonstrating a statistically significant reduction (p<0.0001) in the proportion of patients with RRMS who relapsed at two years compared with placebo. Both doses of BG-12 also met all of the secondary study endpoints, providing a statistically significant reduction in annualized relapse rate, in the number of new or newly enlarging lesions, and in the rate of disability progression as measured by the Expanded Disability Severity Scale (EDSS) at two years.

Topline data also showed that BG-12 demonstrated a favorable safety and tolerability profile. The overall incidence of adverse events and serious adverse events was similar among the placebo group and both BG-12 treatment groups. The safety profile was consistent with what was seen in the published Phase 2 study of BG-12.

BG-12 received Fast Track designation from the U.S. Food and Drug Administration (FDA) in 2008.  Since the DEFINE clinical study has been a placebo-controlled trial, any optimism should be guarded. One must await the results of the follow-up study (CONFIRM) to see if BG-12 represents an advance in the state of the art in multiple sclerosis.  The CONFIRM Phase 3 clinical study is currently underway. This randomized, double blind, actively and placebo- controled trial is evaluating BG-12 and a recently approved drug in MS, glatiramer acetate (Copaxone®, Teva Pharmaceuticals)  against placebo utilizing similar endpoints as those used in the DEFINE study. Results from CONFIRM are expected in the second half of 2011.


October 18, 2010

Phase II study with ocrelizumab shows significant reduction in brain lesions and relapses  for multiple sclerosis patients

Ocrelizumab is a humanized monoclonal antibody designed to selectively target CD20-positive B-cells, which are believed to play a critical role in multiple sclerosis (MS). It then interacts with the body’s immune system to eliminate CD20-positive B-cells. It is jointly developed by Biogen-IDEC and Roche.

The companies announced 24-week results from a phase II study of ocrelizumab in patients with relapsing-remitting multiple sclerosis (RRMS), the most common form of the disease. The study is a randomized, multicenter, 220-patient clinical trial investigating ocrelizumab versus placebo in patients with RRMS although open-label, rater-blinded, interferon beta-1a (Avonex, 30 mcg IM) was also included as a study arm. Efficacy and safety profile of two dose regimens of ocrelizumab (600mg and 2000mg) were evaluated in this study. Patients were treated for 24 weeks and received two ocrelizumab intravenous infusions of 300mg or two intravenous infusions of 1000mg at day 1 and day 15. The primary efficacy endpoint was reduction in brain lesions compared to placebo.  Lesions were observed by magnetic resonance imaging (MRI) scans of the brain at weeks 12, 16, 20 and 24.

Ocrelizumab demonstrated a significant reduction in disease activity as measured by brain lesions and relapse rate. Reductions in total number of brain lesions detected by magnetic resonance imaging (MRI) scans (the primary endpoint of the study) were highly significant at 96% for 2000mg ocrelizumab and 89% for 600mg ocrelizumab compared to placebo . Disease activity was also measured by reduction in annualised relapse rate (ARR), the rate of attacks or flare-ups per patient-year. At week 24, ARR was significantly lowered versus placebo with a reduction of 73% for ocrelizumab 2000mg and 80% for ocrelizumab 600mg.

Both ocrelizumab doses were generally well tolerated and no opportunistic infections were reported.    Serious adverse events (SAEs) were similar in all treatment groups. Infusion-related events during first infusion, predominantly mild to moderate, were more common with ocrelizumab (34.5% and 43.6%) than placebo (9.3%). However, these reports decreased during the second ocrelizumab infusion and were comparable to those initially reported with placebo.

April 14, 2010

Baxter International reports data from a Phase 2 study of Gammagard® in Alzheimer's disease:

Gammagard®, Baxter's intravenous human immunoglobulin concentrate, was evaluated in patients with mild-to-moderate Alzheimer's disease in a limited double-blind, placebo-controlled Phase 2 study.  Enrolled patients (n = 24) received either Gammagard® or placebo intravenously for a period of 6 months followed by a 4-6 week washout period.  After this period, patients were maintained on Gammagard® for a total treatment period of 18 months. Cognition and function were assessed by the Alzheimer’s Disease Assessment Scale-Cognitive Subscale score (ADAS-Cog) and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change Scale (ADCS-CGIC). After 18 months, patients who received Gammagard® continuously (n=14) averaged approximately 1.36 points higher than patients (n=7) who initially received placebo (-0.64 vs. -2.0, p=0.011) on the ADCS-CGIC. Also, the patients who received Gammagard® continuously declined by approximately 9.15 fewer ADAS-Cog points than patients who initially received placebo (approximately 6 point decline vs. 15 point decline, p=0.013).  Patients treated continuously with Gammagard® also showed improvement in secondary outcome measures such as lower ventricular enlargement rates in their brains and lower mean annual whole brain atrophy.  Brain atrophy rates correlated with clinical outcomes.  A Phase 3 study of Gammagard® (the Gammaglobulin Alzheimer’s Partnership (GAP) Study) is currently ongoing.

Genzyme reports follow-up data from the Phase 2 study of alemtuzumab in multiple sclerosis (MS): Alemtuzumab is a monoclonal antibody that targets in a selective fashion, targets T- and B-lymphocytes while largely sparing other immune system elements. These lymphocytes mistakenly attack the myelin sheath that protects nerve cells in MS patients.  The phase 2 study compared annual treatments cycles with alemtuzumab to subcutaneous interferon beta-1a (Rebif®)at a dose of 44 µg three times per week. Treatment was to last for three years.  The study commenced in 2002 but alemtuzumab treatment was discontinued in 2005 because 3 patients developed immune thrombocytopenic purpura (ITP), one of whom died. Results of the study, published in NEJM in 2008, illustrated that alemtuzumab  reduced significantly the rate of sustained accumulation of disability as compared with interferon beta-1a (9.0% vs. 26.2%) but was associated with autoimmunity, manifesting as immune thrombocytopenic purpura. The follow-up four-year data show that an estimated 71% of alemtuzumab-treated patients were free of clinically-active disease, compared to 35 percent of patients taking Rebif® (p<0.001). Overall, six alemtuzumab treated patients and one Rebif patient in the Phase 2 trial have developed ITP. Approximately 28 percent of alemtuzumab-treated patients developed an autoimmune thyroid-related adverse event. Genzyme is currently performing two phase 3 studies with alemtuzumab.

April 1, 2010

The Clinical Potential of MediciNova's MN-166 Featured in Neurology Articles:

MN-166 (Ibudolast: 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine)) is an anti-inflammatory compound acting mainly as a phosphodiesterase inhibitor.  The compound has been licensed in Japan since 1989. A US patent filed in 2001 and issued in 2002 for its utility in neuroprotection prompted its development in multiple sclerosis (MS).  The public release by MediciNova refers to a recent publication in "Neurology" of an article summarizing the results of a phase 2 clinical trial.  The trial in 297 patients with recurring, relapsing MS showed that although the compound did not have any effect in relapse rate or lesion appearance, it was more successful than control in reducing percentage brain volume change (PBVC) and preventing lesions in becoming persistent black holes (a post hoc analysis).  No further clinical trials are ongoing in this indication.