Biogen Idec Initiates Phase III Clinical Program of Oral Compound BG-12 for Multiple Sclerosis
Biogen Idec announced today that it has initiated the Phase III clinical program of BG-12, an oral fumarate in development for relapsing-remitting multiple sclerosis (MS).
The DEFINE (determination of the efficacy and safety of oral fumarate in relapsing-remitting MS) and CONFIRM (comparator and an oral fumarate in relapsing-remitting MS) studies will include more than 2,000 total patients in North America, Europe and rest of world. These studies have been initiated internationally, and Biogen Idec plans to initiate these studies in the U.S. later this year. DEFINE and CONFIRM are two-year, randomised, multi-center, double-blind, placebo-controlled, dose-comparison studies to determine the safety and efficacy of BG-12 in subjects with relapsing-remitting MS. CONFIRM will also include a glatiramer acetate (Copaxone®) reference comparator arm.
Endpoints of both studies include evaluating the effect of BG-12 on measurements of clinical relapse, the progression of disability, and various MRI measures.
“Earlier studies of BG-12 support its potential as an oral therapy for multiple sclerosis. The extensive Phase III clinical program of BG-12 will provide greater understanding of its promise in MS,” said DEFINE lead investigator Ralf Gold, MD, Professor and Chair of the Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum. “MS is a disease that continues to have an unmet need for safe and effective oral therapeutic options.”
“The development of BG-12 furthers Biogen Idec’s commitment to advancing the treatment of MS. We have a diverse portfolio of therapeutic candidates and are dedicated to the pursuit of innovative research that will yield multiple options for people living with this devastating disease,”said Alfred Sandrock, MD, PhD, Senior Vice President, Neurology Research and Development, Biogen Idec.
BG-12 Phase II Study Results
Data from a Phase II study designed to evaluate the efficacy and safety of BG-12 were presented at two European neurological medical meetings in 2006. The Phase II multi-center, double-blind, placebo-controlled, dose-ranging study enrolled 257 patients at sites in 10 countries in Europe. Patients were randomised to receive placebo or BG-12 at 120 mg, 360 mg, or 720 mg per day orally for six months. The patient group treated with 720 mg of BG-12 per day had a 69% reduction (p<0.001) in the mean number of new gadolinium-enhancing lesions versus placebo as measured monthly from weeks 12 to 24 of the study. The 720 mg dose group also had a 48% reduction (p<0.001) in new or newly enlarging T2-hyperintense lesions at six months compared to baseline. Although the study was not powered to achieve statistical significance for this endpoint, there was a 32% reduction (p=0.272) in relapse rate compared to placebo at the 720 mg dose. The results of the 120 mg and 360 mg BG-12-treated groups were not statistically significant versus placebo on any endpoints.
The most common adverse events were flushing, gastrointestinal disorders, headache, and nasopharyngitis. The incidence of liver enzyme elevation greater than or equal to three times the upper limit of normal at any time during the placebo controlled phase of the study was between 2% and 8% in the three active treatment groups, compared with 5% in the placebo group. Improvement in liver enzyme levels was seen after discontinuation of BG-12. The overall rate of infection was the same in the total BG-12-and placebo-treated groups, and no opportunistic infections occurred.
Data suggest that BG-12, an oral fumarate derivative, is an immunomodulator with a novel mechanism of action with a combination of cytoprotective and anti-inflammatory properties. Based on available clinical and scientific information with BG-12 and fumarates, there is strong technical rationale for development of BG-12 in a number of T-cell mediated autoimmune and/or inflammatory diseases.
Source: Biogen Idec