Abstract: Effect of BG-12 (Dimethyl Fumarate) in Newly Diagnosed Relapsing Remitting MS Patients (The 27th Annual Meeting of the CMSC and the 5th Cooperative Meeting of the CMSC-ACTRIMS)

Thursday, May 30, 2013

J. Theodore Phillips, MD PhD FAAN , Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX, USA, Dallas, TX

Ralf Gold, MD , St Josef Hospital, Ruhr University, Bochum, Germany, Bochum, Germany

Gavin Giovannoni, PhD , Queen Mary University of London, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK, London, United Kingdom

Robert J. Fox, MD, FAAN , Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH

Annie Zhang, BM, MPH , Biogen Idec Inc., Weston, MA, USA, Weston, MA

Leslie Meltzer, PhD , Biogen Idec Inc., Weston, MA, USA, Weston, MA

Nuwan C Kurukulasuriya, PhD , Biogen Idec Inc., Weston, MA, USA, Weston, MA

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Background: BG-12 (dimethyl fumarate) demonstrated consistent clinical and radiological efficacy across a broad range of patients with relapsing-remitting multiple sclerosis (RRMS) in BG-12 clinical trials.

Objectives: To evaluate the impact of BG-12 on the clinical efficacy in the newly diagnosed RRMS patient population from the DEFINE and CONFIRM trials.

Methods: Patients included in these post-hoc analyses were diagnosed with RRMS within one year of entry into DEFINE or CONFIRM and were naive to treatment with a disease-modifying therapy. Treatment efficacy was assessed by annualized relapse rate (ARR) and time to first relapse over 2 years. Annualized relapse rate was analyzed using a negative binomial model, and time to relapse was analyzed using a Cox proportional hazards model adjusted for the number of relapse(s) one year prior to study entry, baseline age (<40, ³40 years), EDSS score (≤2.0, >2.0), and region.

Results: A total of 678 patients were assigned to either placebo (N=223), BG-12 240 mg twice daily (BID) (N=221), or BG-12 240 mg three times daily (TID) (N=234). Baseline demographic and clinical characteristics were similar across treatment groups. A median (range) of 2.0 (0-31.0), 2.0 (0-42.0), and 2.0 (0-23.0) years had elapsed since first MS symptoms, and 1.0 (0-1.0) year had elapsed since diagnosis in each of the placebo, BG-12 BID, and BG-12 TID groups. Annualized relapse rate in the newly diagnosed population over 2 years was 0.38 (95% CI 0.30-0.50) in the placebo group compared with 0.17 (0.12-0.23) in the BG-12 BID group and 0.15 (0.11-0.21) in the BG-12 TID group. At 2 years, BG-12 BID and BG-12 TID reduced ARR versus placebo by 56% (rate ratio 0.44 [95% CI 0.30.-0.65]) and by 60% (0.40 [0.27-0.58]), respectively. The proportion of subjects relapsed over two years was 42.2% in the placebo group compared with 21.3% in the BG-12 BID group and 20.5% in the BG-12 TID group using the Kaplan-Meier method. The risk of relapse at two years was reduced by 54% (hazard ratio 0.46 [0.32-0.67]) and 57% (0.43 [0.30- 0.62]) in the BG-12 BID and BG-12 TID groups versus placebo, respectively.

Conclusions: BG-12 demonstrated strong treatment effect on ARR and time to first relapse in the newly diagnosed MS population. Together with an acceptable safety profile in the overall population, this analysis further supports the potential for BG-12 to become a valuable oral treatment option for newly diagnosed RRMS patients.

DX49 Effect of BG-12 (Dimethyl Fumarate) in Newly Diagnosed Relapsing Remitting MS Patients