Week 144 Results of a Phase II, Randomized, Multicenter Trial Assessing the Safety and Efficacy of Ocrelizumab in Patients with Relapsing–Remitting Multiple Sclerosis (RRMS) (S31.004)

BACKGROUND: A Phase II RRMS trial showed that ocrelizumab (OCR) reduced Gd+ lesions by >89% and annualized relapse rate (ARR) by >73% vs placebo at Week 24. Week 144 data are presented here. DESIGN/METHODS: At baseline, 220 RRMS patients were randomized 1:1:1:1 to intravenous OCR 600 mg (A); OCR 2000 mg (B); placebo (C); or open-label intramuscular IFN beta-1a 30 μg (D). At Weeks 24, 48, and 72 all patients received OCR: groups A, C, and D received 600 mg per cycle; group B received 1000 mg at Weeks 24 and 48, switching to 600 mg at Week 72. After 96 weeks, patients went into follow-up (FU). RESULTS: Across groups, 86–91% of randomized patients entered FU after 96 weeks, including patients who had withdrawn from treatment. 67–78% of patients completed to Week 144. Safety: Rates of AEs, SAEs, and serious infections with both OCR doses were similar to placebo during the double-blind period and did not increase throughout the study. Two patients died in FU, 14 and 19 months after last OCR administration (both were B-cell repleted; events unrelated to OCR). No new serious infections were reported since last OCR administration. Efficacy: Between Weeks 96 and 144, 1/69 patients in group B experienced new Gd+ T1 lesions (n=11 lesions) and 2/69 patients had new or newly enlarging T2 lesions (n=3; n=32 lesions). No group A patients had any newly active lesions. ARR for OCR 600 mg after ≥3 cycles was 0.035-0.189 between Weeks 96 and 144 (irrespective of B-cell status). Between Weeks 96 and 144, 6/160 patients had 12 weeks9 confirmed sustained disease progression. CONCLUSIONS: In this open-label extension study, patients followed for up to 72 weeks after last OCR dose experienced very little new MRI activity, low clinical disease activity, and no new safety concerns. Supported by: F. Hoffmann-La Roche Ltd. Disclosure: Dr. Hauser has received personal compensation for activities with BioMarin and Receptos. Dr. Hauser has received personal compensation in an editorial capacity for Annals of Neurology. Dr. Hauser holds stock and/or stock options in Receptos. 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, and Sanofi-Aventis. Dr. Calabresi has received personal compensation for activities with Biogen Idec, Teva Neuroscience, Genzyme Corporation, Vaccinex, Vertex, and Novartis. Dr. Calabresi has received research support from the National Institutes of Health, the National Multiple Sclerosis Society, Nancy Davis Foundation, Biogen Idec, Vertex, Genentech, Inc., Abbott, and Bayer. Dr. O9Connor has received personal compensation for activities with Biogen Idec, EMD Serono, Novartis, Roche, Genzyme Corporation, and Teva Neuroscience. Dr. O9Conner has received research support from Biogen Idec, Novartis, Roche, Genzyme Corporation, and Teva Neuroscience. Dr. Bar-Or has received personal compensation for activities with Amplimmune, Aventis Pharmaceuticals Inc., Bayhill Therapeutics, Berlex, Bayer, Biogen Idec, BioMS, Diogenix, Eli Lilly & Company, Genentech, Inc., Genzyme Corporation, GlaxoSmithKline, Inc., Guthy-Jackson/GGF, EMD Serono, Medimmune, Mitsubishi Pharma, Novartis, Ono Pharma, Receptos, Roche Diagnostics, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, and Wyeth Pharmaceuticals. Dr. Bar-Or has received research support Aventis Pharmaceuticals Inc., Bayhill Therapeutics, Biogen Idec, Berlex, Eli Lilly & Company, Genentech, Inc. GlaxoSmithKline, Inc., Ono Pharma, Diogenix, Roche Diagnostics,, Merck Serono, Novartis, and Teva Neuroscience. Dr. Barkhof has received personal compensation for activities with Novartis, Biogen Idec, Sanofi-Aventis Pharmaceuticals, Inc., Roche Diagnostics Corporation, Merck Serono, and Bayer. Dr. Sauter has received personal compensation for activities with F. Hoffmann-La Roche Ltd as an employee. Dr. Leppert has received personal compensation for activities with F. Hoffmann-La Roche Ltd. as an employee. Dr. Leppert holds stock in F. Hoffmann La Roche Ltd. Dr. Masterman has received personal compensation for activities with F. Hoffmann-La Roche Ltd as an employee. Dr. Masterman holds stock and/or stock options in F. Hoffmann-La Roche. Dr. Tinbergen has received personal compensation for activities with F. Hoffmann-La Roche Ltd. as an employee. Dr. Kappos has receied personal compensation for activities with Actelion, Advancell, Allozyne, BaroFold, Bayer Health Care Pharmaceuticals, Bayer Schering Pharma, Bayhill, Biogen Idec, BioMarin, CLC Behring, Elan, Genmab, Genmark, GeNeuro SA and GlaxoSmithKline. Dr. Kappos has received research support from has received research support from Acorda, Actelion, Allozyne, BaroFold, Bayer HealthCare, Bayer Schering, Bayhill Therapeutics, Biogen Idec, Boehringer Ingelheim, Eisai, Elan, Genmab, GlaxoSmithKline, Glenmark, Merck Serono, MediciNova and Nova.