BG-12 Increases the Proportion of Patients Free of Clinical and Radiologic Disease Activity in Relapsing-Remitting Multiple Sclerosis: Findings from the DEFINE Study (PD5.005) (2012)

Objective: To evaluate the impact of BG-12 (dimethyl fumarate) on the proportion of patients with relapsing-remitting multiple sclerosis (RRMS) who were free of clinical or magnetic resonance imaging (MRI) disease activity in the Phase 3 DEFINE study. Background DEFINE was a 2-year randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of BG-12 in patients with RRMS. In DEFINE, BG-12 significantly reduced clinical relapses, disability progression, and MRI measures of disease activity. Design/Methods: Patients aged 18-55 years with a diagnosis of RRMS and an Expanded Disability Status Scale (EDSS) score of 0.0-5.0 were included in the study. Patients were randomly assigned 1:1:1 to placebo, BG-12 240 mg twice daily (BID) or three times daily (TID). In the current analysis, absence of disease activity over 2 years was analyzed as follows: clinical (no relapses or EDSS progression), radiologic (no new or newly enlarging T2 lesions and gadolinium-enhancing lesions), and overall (no clinical and radiologic disease activity). Analyses of disease-free measures were performed on the MRI cohort using a chi-square test and logistic regression model. Results: The analysis included 469 patients with MRI measures. The proportion of disease-free patients over 2 years was significantly higher in both BG-12 treatment groups versus placebo: clinical (BID 63% and TID 59% vs placebo 39%; P P P Conclusions: Findings from this subset analysis of DEFINE indicate that BG-12 demonstrated a significant treatment effect on clinical, radiologic, and overall disease-free activity compared with placebo over 2 years in patients with RRMS. Supported by: Biogen Idec Inc. Disclosure: 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. 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. 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. Selmaj has received personal compensation for activities with Genzyme, Ono, and Biogen Idec. Dr. Zhang has received personal compensation for activities with Biogen Idec as an employee. Dr. Sheikh has received personal compensation for activities with Biogen Idec as an employee. Dr. Dawson has received personal compensation for activities with Biogen Idec Inc. as an employee.