Long-Term Efficacy and Safety of Ocrelizumab in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS): Week 96 Results of a Phase II, Randomized, Multicenter Trial (S30.006)

Objective: Ocrelizumab reduced gadolinium-enhancing lesions (primary endpoint) by ≥89% and annualized relapse rate (ARR) by ≥73% vs placebo by Week 24, in a Phase II trial in RRMS. Background To determine long-term efficacy and safety of ocrelizumab up to Week 96. Design/Methods: RRMS patients (n=220) were randomized (1:1:1:1) to intravenous ocrelizumab (days 1, 15) total dose 600 mg (A), 2000 mg (B), placebo (C), or open-label weekly intramuscular interferon beta-1a 30 μg (D). At Weeks 24, 48, and 72, all patients received open-label ocrelizumab: groups A, C, and D received 600 mg/cycle; group B received 1000 mg at Weeks 24 and 48, then 600 mg at Week 72. MRI follow-up occurred only with groups A and B. Results: 183 patients completed 96 weeks. From Weeks 0–96, the ARR was 0.18 [95% CI: 0.11–0.31] and 0.22 [95% CI: 0.13–0.35] for groups A and B; 78.2% and 80.0% of patients, respectively, were relapse-free and 67.3% and 76.4% had no relapses or confirmed EDSS progression (9clinical disease activity free9). ARRs reduced during Weeks 24 to 96 in patients switched from placebo to ocrelizumab (group C) from 0.64 to 0.20 [95% CI: 0.12–0.33] and from 0.36 to 0.16 [95% CI: 0.09–0.28] in those switched from interferon beta-1a to ocrelizumab (group D). At Week 96 there were no gadolinium-enhancing lesions in groups A and B with 1.1% and 1.2% reduction in brain volume, respectively, from Weeks 12–96. Serious infection rates were similar for all groups and did not increase with time on treatment. There were no opportunistic infections or imbalance in rate of serious adverse events across groups over 96 weeks. Conclusions: Ocrelizumab substantially reduced MRI and clinical measures of MS disease activity over 96 weeks. Switching from interferon beta-1a or placebo to ocrelizumab produced similar sustained benefits. Disclosure: Dr. Hauser has received personal compensation for activities with BioMarin, Novartis and Receptos as a consultant and serving on a scientific advisory board.Dr. Hauser has received personal compensation in an editorial capacity for the journal Annals of Neurology and Harrison9s Internal Medical textbook.Dr. Hauser has received compensation for serving on the scientific advisory board of Receptos. 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. Li has received personal compensation for activities with Genzyme, Novartis and Nuron as a consultant.Dr. Li has receved research support from Angiotech, Bayer, Berlex-Schering, Bio-MS, Boehringer-Ingelheim, Centocor, Daiichi Sankyo, Genentech, Hoffmann-LaRoche, Merck-Serono, Perceptives, Schering-Plough, Teva Neurosciences,Sanofi-Aventis, Transition Therapeutics, and Novartis. Dr. Calabresi has received personal compensation for activities with Teva, Biogen Idec, Novartis, Genzyme, Johnson & Johnson, and Vertex. Dr. Calabresi has received research support from Biogen Idec, Teva, EMD Serono, Vertex, Genentech, Abbott, and Bayer. Dr. O9Connor has received personal compensation for activities with Abbott Labratories, Inc., Bayer Pharmaceuticals Corporation, Biogen Idec, BioMS, Cognosci, Daiichi Pharmaceuticals Corporation, Serono, Inc., Genentech, Inc., Genmab, Novartis, Roche Diagnostics Corporation, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, Warburg Pincus and Wyeth Pharmaceuticals as a consultant. Dr. O9Connor has received research support from Abbott Labratories, Bayer Pharmaceuticals Corporation, Biogen Idec, BioMS, Cognosci, Daiichi Pharmaceutical Corporation, Serono, Inc., Genentech, Inc., Genmab, Novartis, Roche Diagnostics Corporation, Sanofi-Aventis Pharmaceuticals, Teva Neuroscience, Warburg Pincus and Wyeth Pharmaceuticals. 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. Barkhof has received personal compensation for activities with Novartis, Biogen Idec, Merck-Serono, and Bayer-Schering as a consultant. Mr. Wells has received personal compensation for activities with Roche as an employee. Dr. Leppert has received personal compensation for activities with Roche Diagnostics Corporation as an employee. Dr. Leppert has received compensation for serving on the University of British Columbia MS/MRI Research Group of Angiotech, Bayer, Berlex-Schering, Bio-MS, Centocor, Daiichi Sankyo, Genentech, Hoffmann-LaRoche, Merck-Serono, Perceptives, Schering-Plough, Teva Neurosciences, Sanofi-Aventis, and Transition Therapeutics. Dr. Leppert holds stock and/or stock options in F. Hoffmann La Roche Ltd., which sponsored research in which Dr. Leppert was involved as an investigator. Dr. Glanzman has received personal compensation for activities with Hoffmann-LaRoche LTD. Dr. Tinbergen has received personal compensation for activities with Roche Diagnostics Corporation as an employee. Dr. Tinbergen holds stock and/or stock options in Roche Diagnostics Corporation.