Efficacy and Safety Results from Comparison of Alemtuzumab and Rebif(R) Efficacy in Multiple Sclerosis II (CARE-MS II): A Phase 3 Study in Relapsing-Remitting Multiple Sclerosis Patients Who Relapsed on Prior Therapy (S01.004)

Objective: Evaluate the effect of alemtuzumab on relapse and disability versus subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis (RRMS) patients who have relapsed on prior therapy. Background Alemtuzumab was significantly more effective than SC IFNB-1a in two clinical trials with treatment-naive RRMS patients. Treatment options are limited for RRMS patients experiencing disease activity during therapy, and few controlled studies have been conducted to determine their appropriate management. Design/Methods: CARE-MS II is a 2-year rater-blinded trial with RRMS patients who have relapsed during prior therapy. Alemtuzumab treatment was 12 mg/day (or 24 mg/day in an exploratory cohort) by intravenous administration for 5 days at study start and 3 days one year later. IFNB-1a treatment was 44 mcg SC 3-times weekly throughout the study. Entry criteria included 18-55 years of age, MS symptom onset within 10 years, and Expanded Disability Status Scale (EDSS) score ≤5. Primary endpoints include relapses adjudicated by an independent panel and time to sustained accumulation of disability assessed by blinded evaluators. Results: 840 patients from 180 centers in 23 countries were randomized. Baseline characteristics (mean) were: age 35 years; disease duration 3.9 years; EDSS 2.7; with 1.6 and 2.7 relapses in 1 and 2 years prior to study entry, respectively. The most common prior MS therapies were interferon-beta (78.6%) or glatiramer acetate (32.5%); less than 5% of patients had received other prior MS therapy (some patients received more than one therapy). Conclusions: Database lock and study analysis will occur in late 2011. The principal efficacy and safety results will be presented. ®Rebif is a registered trademark of EMD Serono, Inc. Supported by: Genzyme, a Sanofi company and Bayer Healthcare Pharmaceuticals. Disclosure: Dr. Cohen has received personal compensation for activities with Biogen Idec, Eli Lilly & Company, Novartis, and Vaccinex. Dr. Cohen has received research support for activities with Biogen Idec, BioMS, Genzyme Corporation, Novartis, Synthon, and Teva Neuroscience. Dr. Twyman has received personal compensation for activities with Genzyme Corporation as a consultant, speaker and participant on advisory boards. Dr. Twyman has received research support from Genzyme Corporation. 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. Coles has received personal compensation for activities with Genzyme Corporation, GlaxoSmithKline, Inc., and Merck Serono as a consultant and/or speaker. Dr. Coles has received research support from Genzyme Corportation. Dr. Confavruex has received personal compensation for activities with Biogen Dompe, Biogen Idec, Gemacbio, Genzyme Corporation, Hertie Foundation, Novartis, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, UCB Pharma, Bayer Schering, and Merck Serono. Dr. Confavruex has received research support from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis Pharmaceuticals, and Teva Neuroscience. Dr. Fox has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, EMD Serono, Genzyme Corporation, Novartis, Opexa Therapeutics, Pfizer Inc, and Teva Neuroscience. Dr. Fox has received personal compensation in an editorial capacity for Neura. Dr. Fox has received research support from Biogen Idec, Eli Lilly & Company, EMD Serono, Genzyme Corporation, Novartis, Ono Pharmaceutical, Roche Diagnostics Corporation, Sanofi-Aventis Pharmaceuticals, Inc., and Teva Neuroscience. Dr. Hartung has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, BioMS, Genzyme Corporation, Merck Serono, Novartis, Sanofi-Aventis and Teva as a speaker and/or consultant. Dr. Havrodova has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Genzyme Corporation, GlaxoSmithKline, Inc., Novartis, Merck, Sanofi-Aventis Pharmaceuticals, Serono, Inc., and Teva as consultant, speaker and/or advisory board participant. Dr. Selmaj has received personal compensation for activities with Genzyme, Ono, and Biogen Idec. Dr. Weiner has received personal compensation for activities with Biogen Idec, Novartis, Serono, Inc., Teva Neurosciences, GlaxoSmithKline, Nasvax, Xenoport and Genzyme Corporation as consulting and/or speaking activities. Dr. Weiner has received research support from Merck Serono. Dr. Miller has received personal compensation for activities with Allergan, Bayer, Biogen Idec, Eli Lilly, EMD Serono, Forest, Novartis, Sanofi Aventis, and Teva as a speaker. Dr. Miller has received research support from Allergan, Biogen Idec, Genzyme, Elan, Teva, Novartis, Ono, Sanofi Aventis, EMD Serono, and Roche-Genetech. Dr. Lake has received personal compensation for activities with Genzyme as an employee. Dr. Margolin has received personal compensation for activities with Genzyme Corporation as an employee. Dr. Panzara has received personal compensation for activities with Biogen Idec as an employee.Dr. Panzara holds stock and/or stock options in Biogen Idec. Dr. Compston has received personal compensation for activities with Genzyme Corporation as a speaker. Dr. Compston has received research support from Genzyme Corporation.