Clinical Efficacy of BG-12 (Dimethyl Fumarate) in Relapsing–Remitting Multiple Sclerosis (RRMS): An Integrated Analysis of the Phase 3 DEFINE and CONFIRM Studies (P07.097)

OBJECTIVE: To report a pre-specified integrated analysis of clinical efficacy data from DEFINE and CONFIRM, which was conducted to obtain more precise estimates of the treatment effect of BG-12 (dimethyl fumarate) versus placebo. BACKGROUND: In clinical studies, dimethyl fumarate has demonstrated efficacy in patients with RRMS. DESIGN/METHODS: Eligibility criteria included age 18–55 years, a diagnosis of RRMS (McDonald criteria) and an Expanded Disability Status Scale (EDSS) score of 0–5.0. Patients receiving oral dimethyl fumarate 240 mg twice (BID) or three times daily (TID) or placebo were included in the integrated analysis. The primary endpoints for DEFINE and CONFIRM were the proportion of patients relapsed and annualized relapse rate (ARR) at 2 years, respectively. Disability progression at 2 years was a secondary clinical endpoint in both studies. The integrated analysis, using identical endpoints, was to be conducted only if baseline characteristics and treatment effects were homogeneous across studies. RESULTS: A total of 2,301 patients were randomized: dimethyl fumarate BID (n=769), TID (n=761), placebo (n=771). Baseline characteristics and treatment effects were consistent across studies. Compared with placebo, dimethyl fumarate BID and TID reduced ARR at 2 years by 49% (both p CONCLUSIONS: Both doses of dimethyl fumarate significantly reduced clinical relapses and disability progression over 2 years compared with placebo. Together with an acceptable safety profile, this integrated analysis further supports the potential for dimethyl fumarate to become a valuable oral treatment option for patients with RRMS. Supported by: Biogen Idec Inc. Disclosure: Dr. Fox has received personal compensation for activities with Avanir, Biogen Idec, EMD Serono, and Novartis. Dr. Fox has received research support from Biogen Idec and Genentech. Dr. Miller has received personal compensation for activities with UCL Institute of Neurology, Biogen Idec, GlaxoSmithKline, and Bayer Schering Pharma. Dr. Miller has received personal compensation in an editorial capacity for Journal of Neurology. Dr. Miller has received research support from UCL Institute of Neurology, from Biogen Idec, Schering AG, Apitope, Richmond Pharma, GlaxoSmithKline, and Novartis. Dr. Phillips has received personal compensation for activities with Biogen Idec, Genzyme, Novartis, and Teva. Dr. Phillips has received research support from Roche. Dr. Arnold has received personal compensation or research support from Bayer Healthcare, Biogen Idec, Genetech, NeuroRx Research, Roche, Schering, Serono, and Teva Neuroscience. Dr. Arnold has received personal compensation or research support for Bayer Healthcare, Biogen Idec, Genetech, NeuroRx Research, Roche, Schering, Serono, and Teva Neuroscience. Dr. Selmaj has received personal compensation for activities with Biogen Idec, Genzyme, Ono Pharmaceutical, Novartis, Bayer, Hoffmann LaRoche, Merck, Serono and Synthon. Ms. Yang has received personal compensation for activities with Biogen Idec as an employee. Ms. Yang holds stock and/or stock options in Biogen Idec. Ms. Yang has received research support in Biogen Idec. Dr. Zhang has received personal compensation for activities with Biogen Idec Inc. as an employee. Dr. Zhang holds stock and/or stock options in Biogen Idec. Dr. Zhang has received research support from Biogen Idec. Dr. Dawson has received personal compensation for activities with Biogen Idec as an employee. Dr. Dawson holds stock and/or stock options in Biogen Idec. Dr. Dawson has received research support from Biogen Idec. Dr. Viglietta has received personal compensation for activities with Biogen Idec as an employee. Dr. Viglietta has received research support from Biogen Idec. Dr. Sheikh has received personal compensation for activities with Biogen Idec as an employee. Dr. Sheikh has received research support from Biogen Idec. Dr. Gold has received personal compensation for activities with Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. Dr. Gold has received personal compensation in an editorial capacity for Therapeutic Advances in Neurological Disorders. Dr. Gold has received a license fee from Biogen Idec. Dr. Gold has received research support from Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience.