Abstract: Timecourse of Treatment Effects of BG-12 (Dimethyl Fumarate) in MS (The 27th Annual Meeting of the CMSC and the 5th Cooperative Meeting of the CMSC-ACTRIMS)

Thursday, May 30, 2013

Ludwig Kappos, MD , University Hospital, Basel Neurology, Basel, Switzerland, Basel, Switzerland

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

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

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

Christophe Hotermans, MD, PhD , Biogen Idec Inc., Weston, MA, USA, Weston, MA

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

Vissia Viglietta, MD , Biogen Idec Inc., Weston, MA, USA, Cambridge, MA

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

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Background: BG-12 (dimethyl fumarate) significantly reduced relapses and brain magnetic resonance imaging (MRI) activity over 2 years in relapsing–remitting MS (RRMS) patients in DEFINE and CONFIRM.

Objectives: To characterize the temporal profile of BG-12 treatment effects in an integrated analysis of data from the Phase 3 DEFINE and CONFIRM studies.

Methods: Patients with RRMS receiving oral BG-12 240 mg twice (BID) or three times daily (TID) or placebo in both studies were included in the analyses. Primary endpoints were proportion of patients relapsed (DEFINE) and annualized relapse rate (ARR; CONFIRM). MRI was performed at baseline and Weeks 24, 48 and 96, in a subset of patients (MRI cohort).

Results: The intent-to-treat population for the integrated analysis comprised 769, 761 and 771 patients assigned to BG-12 BID, TID and placebo, respectively (MRI cohort: 345, 354 and 347 patients, respectively). BG-12 treatment reduced the proportion of patients relapsed and ARR, with significant separation versus placebo achieved at Week 12 (post-hoc analyses). The hazard ratio (95% confidence interval [CI]) for risk of relapse at Week 12 was 0.68 (0.48, 0.96) in the BID group (p=0.0282) and 0.70 (0.50, 0.99) in the TID group (p=0.0455). The rate ratio (95% CI) for ARR at Week 12 was 0.66 (0.47, 0.92) (BID; p=0.0149) and 0.69 (0.49, 0.96) (TID; p=0.0299). Significant separation was maintained thereafter; by 2 years, BG-12 BID and TID reduced risk of relapse by 43% and 47% versus placebo, and ARR by 49% for both (all p<0.0001). BG-12 treatment significantly reduced gadolinium-enhancing (Gd+) lesion activity versus placebo at the first post-baseline MRI assessment at Week 24; the odds ratio (95% CI) was 0.06 (0.02, 0.13) in the BID group and 0.19 (0.11, 0.35) in the TID group (both p<0.0001). At 2 years, reductions in Gd+ lesion activity were 90% and 73% in the BID and TID groups, respectively, versus placebo (both p<0.0001).

Conclusions: BG-12 treatment resulted in significant improvements in clinical disease activity and MRI activity over placebo that were apparent by 12 and 24 weeks, respectively, and sustained over 2 years.

DX40 Timecourse of Treatment Effects of BG-12 (Dimethyl Fumarate) in MS