5th Joint triennial congress of the European and Americas Committees
for Treatment and Research in Multiple Sclerosis
Amsterdam, The Netherlands

19.10.2011 - 22.10.2011
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Home - 21.10.2011 - Platform presentation of selected abstracts on therapeutics

Platform presentation of selected abstracts on therapeutics

Friday, October 21, 2011, 09:30 - 09:45

Clinical efficacy of BG-12, an oral therapy, in relapsing-remitting multiple sclerosis: data from the phase 3 DEFINE trial

R. Gold, L. Kappos, A. Bar-Or, D. Arnold, G. Giovannoni, K. Selmaj, M. Yang, K. Dawson (Bochum, DE; Basel, CH; Montreal, CA; London, GB; Lodz, PL; Cambridge, US)

Background: BG-12 (dimethyl fumarate) is an experimental oral treatment for relapsing-remitting multiple sclerosis (RRMS) that may have dual anti-inflammatory and neuroprotective effects via the Nrf2 pathway. In a Phase 2b trial, BG-12 reduced inflammatory activity in patients with RRMS.
Objective: To report the effects of BG-12 on clinical efficacy endpoints in the Phase 3 DEFINE (Determination of the Efficacy and Safety of Oral Fumarate in Relapsing-Remitting MS) study.
Methods: DEFINE was a randomised, double-blind, placebo-controlled, multicentre clinical trial that evaluated the efficacy and safety of BG-12 over 2 years in patients with RRMS. Patients aged 18-55 years with McDonald criteria diagnosis of RRMS and an Expanded Disability Status Scale (EDSS) score of 0.0-5.0 (inclusive) were randomly assigned on a 1:1:1 basis to placebo, BG-12 240 mg PO twice daily (BID), or BG-12 240 mg three times daily (TID). All subjects underwent clinical assessments at screening, baseline, and every 4 weeks for up to 2 years. The primary endpoint was proportion of patients relapsing at 2 years, with relapses confirmed by an independent neurology evaluation committee to ensure consistent and accurate reporting across sites. Secondary clinical efficacy endpoints at 2 years were annualised relapse rate (ARR) and disability progression using EDSS. Efficacy analyses were conducted on the intention-to-treat population.
Results: A total of 1234 patients were dosed with placebo (n=408), BG-12 BID (n=410), or BG-12 TID (n=416), with similar demographic and clinical characteristics across treatment groups. All primary and secondary endpoints of the study were met. BG-12 BID and TID reduced the risk of relapse by 49% and 50%, respectively, compared with placebo (P<0.0001) at 2 years. ARR was 0.36 with placebo, and 0.17 and 0.19 with BG-12 BID and TID, corresponding to reductions of 53% and 48% for BG-12 BID and TID (P<0.001). The risk of confirmed 12-week disability progression was reduced by 38% with BG-12 BID (P<0.01) and by approximately 34% with BG-12 TID (P<0.05). The overall incidence of adverse and serious adverse events was similar among the placebo group and both BG-12 treatment groups.
Conclusions: The results from this large Phase 3 study support the potential of BG-12 as an effective oral treatment for patients with RRMS that has a novel mechanism of action.

Supported by Biogen Idec Inc. R. Gold: honoraria from Bayer Health Care, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience; research support from Bayer Health Care, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. L. Kappos: research support from Acorda, Actelion, Allozyne, BaroFold, Bayer HealthCare Pharmaceuticals, Bayer Schering, Bayhill Therapeutics, Biogen Idec, Boehringer Ingelheim, Eisai, Elan, Genmab, Glenmark, GlaxoSmithKline, Merck-Serono, MediciNova, Novartis, sanofi-aventis, Santhera, Shire, Roche, Teva Neuroscience, UCB, Wyeth, Swiss MS Society, Swiss National Research Foundation, European Union, Gianni Rubatto Foundation, Novartis, and Roche Research Foundations. A. Bar-Or: honoraria from Aventis, Biogen Idec, Bayhill Therapeutics, Berlex, Diogenix, Eli-Lilly, Genentech, GlaxoSmithKline, Merck Serono, Novartis, Ono Pharma, Roche, and Teva Neuroscience. D. Arnold: honoraria from Bayer Health Care, Biogen Idec, Genentech, NeuroRx Research, Roche, Schering, Serono, and Teva Neuroscience; research support from Teva Neuroscience. G. Giovannoni: honoraria from Bayer Health Care, Biogen Idec, Canbex, Genzyme, GlaxoSmithKline, Merck-Serono, Novartis, Protein Discovery Laboratories, Roche, Synthon, Teva Neuroscience, and UCB. K. Selmaj: honoraria from Biogen Idec, Genzyme, Novartis, Ono Pharma, and Roche. M. Yang and K. Dawson: employees of Biogen Idec.