Effect of BG-12 on Brain Atrophy and Lesions Volume: MRI Results from the DEFINE Study during First and Second Year of Treatment (IN3-2.002)

Abstract

Objective: To report results of BG-12 on tertiary magnetic resonance imaging (MRI)-related outcomes from the Phase 3 DEFINE study. Background BG-12 is an experimental oral treatment for relapsing-remitting multiple sclerosis (RRMS) that may have anti-inflammatory and neuroprotective effects via the Nrf2 pathway. DEFINE, a randomized, double-blind, placebo-controlled study evaluating BG-12 over 2 years in RRMS patients, showed significant reductions in clinical relapses, accumulation of disability progression, and number of lesions on brain MRI images. Design/Methods: Patients aged 18-55 years with RRMS (McDonald criteria) and EDSS score of 0.0-5.0 were enrolled. Patients were randomized 1:1:1 to placebo or BG-12 240 mg twice (BID) or three times daily (TID). A subset of patients from 76 sites had MRI scans at baseline, 24 weeks, 1 year, and 2 years. Tertiary endpoints included brain atrophy from 6 months to 2 years measured using the SIENA method and the volume of T2, gadolinium-enhancing (Gd+), and T1 hypointense lesions at 1 and 2 years. Results: The MRI intent-to-treat cohort comprised 540 patients. The median percent whole brain volume change from 6 months to 2 years was -0.660% in placebo compared with -0.460% and -0.550% in the BG-12 BID and TID groups, respectively, representing reductions of 30% (P=0.0214) and 17% (P=0.2478) versus placebo. Over 2 years, the median percent change of T2 hyperintense lesion volume from baseline was 20.1% with placebo versus -6.2% (P Conclusions: Results of the MRI analysis of the DEFINE study demonstrate reduced brain atrophy and lesion volume compared with placebo and supports BG-129s potential as an effective oral treatment for RRMS patients. Supported by: Biogen Idec Inc. Disclosure: 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. 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. 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. 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. 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. Stephan has received personal compensation for activities with Biogen Idec as an employee. Dr. Stephan has received research support from Biogen Idec. Dr. Dawson has received personal compensation for activities with Biogen Idec Inc. as an employee.