Effect of BG-12 in Subgroups of Patients with Relapsing-Remitting Multiple Sclerosis: Findings from the DEFINE Study (P01.130) (2012)

Objective: To assess the efficacy of BG-12 in subgroups of patients from the Phase 3 DEFINE study. Background BG-12 is an experimental oral treatment for relapsing-remitting multiple sclerosis (RRMS) that may have anti-inflammatory and neuroprotective effects via the Nrf2 pathway. DEFINE, a randomized, double-blind, placebo-controlled, multicenter study evaluating BG-12 over 2 years in patients with RRMS, showed significant reductions in clinical relapses, accumulation of disability progression, and disease activity on magnetic resonance imaging scans. Design/Methods: Patients 18-55 years with RRMS (McDonald criteria) and an Expanded Disability Status Scale score of 0.0-5.0 were randomized to placebo, BG-12 240 mg twice daily (BID), or BG-12 240 mg three times daily (TID). Subgroup analyses were based on baseline demographic and disease characteristics, including age, relapses in year prior to study entry (≤1 versus ≥2 relapses), prior MS treatment (yes/no), baseline EDSS score (≤ or >2.0), and others. Effects of BG-12 on primary efficacy endpoint and secondary clinical endpoints at 2 years were evaluated. Results: Both doses of BG-12 demonstrated consistent benefits on relapse and disability progression across all subgroups over 2 years. For instance, in patients who had ≤1 relapse in the year prior to study entry, the hazard ratio (HR [95% CI]) for risk of relapse over 2 years was 0.52 [0.38-0.71] for BG-12 BID and 0.51 [0.37-0.70] for BG-12 TID, representing reductions relative to placebo of 48% and 49%, respectively, whereas in patients who had ≥2 relapses in the year prior to study entry, reductions were 49% (0.51 [0.34-0.77]) and 51% (0.49 [0.32-0.74]). Likewise, both BG-12 doses demonstrated positive benefits on annualized relapse rate and disability progression regardless of the number of relapse in the year prior to study entry. Conclusions: BG-12 treatment resulted in reduction of clinical activity across RRMS patients with varied demographic and disease subgroups. Supported by: Biogen Idec Inc. Disclosure: Dr. Bar-Or has received personal compensation for activities with Aventis Pharmaceuticals, Bayhill Therapeutics, Biogen Idec, Berlex Laboratories, Eli Lilly & Company, Genentech, Inc., GlaxoSmithKline, Ono Pharmaceutical, Diogenix, Roche Diagnostics Corporation, Merck Serono, Novartis, Teva Neuroscience. Dr. Gold has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Merck Serono, Teva Neuroscience. Dr. Gold has received personal compensation in an editorial capacity for Therapeutic Advances in Neurological Disorders. Dr. Gold has received (royalty or license fee or contractual rights) payments from Biogen Idec. Dr. Gold has received research support from Bayer Pharmaceuticals Corporation, Biogen Idec, Merck Serono, Novartis and Teva Neuroscience. Dr. Kappos has received research support from Acorda Therapeutics, Actelion, Allozyne, BaroFold, Inc., Bayer Pharmaceuticals Corporation, Bayhill Therapeutics, Biogen Idec, Boehringer Ingelheim Pharmaceuticals, Inc, Elan Corporation, Genmab, GlaxoSmithKline, Inc., Glenmark Pharma, Merck Serono, MediciNova, Novartis, Sanofi-Aventis Pharmaceuticals, Santhera Pharmaceuticals, Shire, Roche Diagnostics, Teva Neuroscience, UCB Pharma, Pfizer Inc, Swiss MS Society, Swiss National Research Foundation, European Union, Gianni Rubatto Foundation, Novartis and Roche Research Foundations. Dr. Arnold has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Genentech, Inc., NeuroRx Research, Roche Diagnostics Corporation, Schering, Serono, Inc., and Teva Neuroscience. Dr. Arnold Dr. Arnold has received research support from Bayer Healthcare, Biogen Idec, Genentech, Inc., NeuroRx Research, Roche Diagnostics Corporation, Schering, Serono, Inc., and Teva Neuroscience. Dr. Giovannoni has received personal compensation for activities with Bayer-Pharmaceuticals Corporation, Biogen Idec, Five Prime Therapeutics, Inc, Genzyme Corporation, Ironwood Pharmaceuticals, Merck Serono, Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals and Vertex Pharmaceuticals as a speaker, consultant and/or serving on data monitoring boards. Dr. Selmaj has received personal compensation for activities with Genzyme, Ono, and Biogen Idec. Dr. O9Gorman has received personal compensation for activities with Biogen Idec as an employee. Dr. Stephan has received personal compensation for activities with Biogen Idec as an employee. Dr. Stephan has received research support from Biogen Idec. Dr. Dawson has received personal compensation for activities with Biogen Idec Inc. as an employee.