The Phase 2b SYNERGY Trial: Analyses of Acute Brain Lesion Recovery (P6.331)

Objective: To investigate the effects of opicinumab on new (acute) lesion recovery using exploratory brain MRI measures of repair. Background: Opicinumab (anti-LINGO-1; BIIB033) is a potential CNS remyelinating agent. The Phase 2b SYNERGY trial (NCT01864148) evaluated the efficacy of opicinumab vs. placebo in participants with pre-existing disability secondary to active relapsing multiple sclerosis. Design/Methods: Randomized participants received intravenous opicinumab 3, 10, 30 or 100 mg/kg or placebo every 4 weeks (19 doses) and concomitant intramuscular interferon beta-1a 30 mcg once weekly for 72–84 weeks. Brain MRIs were acquired at screening and weeks 0, 4, 8, 12, 16, 20, 24, 48, 72 and 84. Standardized image acquisition was implemented across sites with centralized quality control; images were analyzed by a single MRI reading center blinded to treatment assignment. Repair of new lesions was assessed using the following exploratory markers: percentage gadolinium-enhancing (Gd+) lesion volume with increased and decreased magnetization transfer ratio (MTR); percentage of new Gd+ brain lesions converting to chronic black holes; MTR recovery in new Gd+ lesions; diffusion tensor imaging (DTI) recovery (radial diffusivity [RD] and fractional anisotropy [FA]) in new Gd+ lesions. Results: 418 participants were randomized and dosed. Overall, there were 1355 new Gd+ lesions (combined across weeks 4–72 and treatment arms) that were evaluated for individual lesion evolution analyses. Results of opicinumab efficacy on acute lesion recovery will be presented. Conclusions: SYNERGY used conventional MRI as well as DTI and MTR to assess the potential pharmacodynamic effects of opicinumab vs. placebo on new lesion repair. The results to be presented will explore imaging metrics of acute lesion recovery and may identify useful MRI biomarkers of opicinumab treatment response. Study Supported by: Biogen Disclosure: Dr. Evans has received personal compensation for activities with Biogen Idec as an employee. Dr. Evans holds stock and/or stock options in Biogen Idec. Dr. Brown has received personal compensation for activities with NeuroRx Research as a consultant. Dr. Li has received personal compensation for activities with Biogen as an employee. Dr. Li holds stock and/or stock options in Biogen, which sponsored research in which Dr. Li was involved as an investigator. Dr. Xu has received personal compensation for activities with Biogen as an employee. Dr. Xu hold stock and/or stock options in Biogen. Dr. Arnold has received personal compensation for activities with Coronado Biosciences, Consortium of Multiple Sclerosis Centers, Eli Lilly, EMD Serono, Genentech, Genzyme, GlaxoSmithKline, MS Forum, NeuroRx Research, Novartis, Opexa Therapeutics, Roche, Merck Serono, S.A. Serono Symposia International Foundation, Teva, the Canadian Institutes of Health Research, and the Multiple Sclerosis Society of Canada. Dr. Arnold holds stock and/or stock options in NeuroRx Research. Dr. Fisher has received personal compensation for activities with Biogen Idec as an employee. Dr. Fisher has received stock and/or stock options in Biogen Idec. Dr. Naismith has received personal compensation for activities with Acorda, Alkermes, Bayer, Biogen, EMD Serono, Genentech, Genyzme, Novartis, and Teva. Dr. Naismith has received research support from Alkermes. Dr. Boyko has received personal compensation for activities with Biogen Idec, Sanofi-Genzyme, Novartis, Teva, Merck-Serono, and Takeda as a consultant, advisor or speaker. Dr. Evangelou has received personal compensation for activities with Biogen Idec, merck & Co., Inc., Novartis and Roche. Dr. Valis has received personal compensation from Biogen, Krka, and Merck. Dr. Richert has received personal compensation for activities with Biogen as an employee. Dr. Richert holds stock and/or stock options in Biogen. Dr. Cadavid has received personal compensation for activities with Biogen as a holder of stock and/or stock options and as an employee. Dr. Mellion has received personal compensation for activities with Biogen has an employee. Dr. Mellion holds stock and/or stock options with Biogen. Dr. Evans has received personal compensation for activities with Biogen Idec as an employee. Dr. Evans holds stock and/or stock options in Biogen Idec.