Teriflunomide Efficacy and Safety in Patients with Relapsing Multiple Sclerosis: Results from TOWER, a Second, Pivotal, Phase 3 Placebo-Controlled Study (S01.004)

OBJECTIVE: To assess the efficacy and safety of teriflunomide in patients with relapsing forms of multiple sclerosis (RMS) in a second Phase 3 clinical trial (TOWER, NCT00751881). BACKGROUND: Teriflunomide is a novel, once-daily, oral, disease-modifying therapy recently approved in the US for treatment of RMS. In the TEMSO study (NCT00134563), teriflunomide 14mg reduced the annualized relapse rate (ARR) by 31.5% (p DESIGN/METHODS: In TOWER, a double-blind, parallel-group study, 1169 patients with RMS (18–55 years old, Expanded Disability Status Scale score ≤5.5 at screening, and ≥1 or ≥2 relapses in the 12 or 24 months prior to randomization, respectively) were randomized to once-daily placebo, teriflunomide 7mg or 14mg. TOWER had variable treatment duration; the study ended when the last patient randomized completed 48 weeks of treatment. The primary and key secondary endpoints were ARR and 12-week disability progression, respectively. Safety analyses included treatment-emergent adverse events (TEAE), laboratory evaluations, and vital signs. RESULTS: Teriflunomide 14mg significantly reduced ARR by 36.3% (p CONCLUSIONS: Teriflunomide 14mg significantly reduced ARR and 12-week disability progression compared with placebo; 7mg significantly reduced ARR. Teriflunomide has a well-characterized safety profile. These results confirm those of TEMSO and support teriflunomide as a treatment option for patients with RMS. Supported by: Genzyme, a Sanofi company. Disclosure: Dr. Miller has received personal compensation for activities with Acorda Therapeutics, Biogen Idec, GlaxoSmithKline, Merck Serono, Novartis, Nuron Biotech, ONO, Genzyme/Sanofi, Questcor, Teva Neuroscience, and Accordant Health Services. Dr. Miller has received personal compensation for activities in an editorial capacity for Continuum and Continuum Audio. Dr. MIller has received research support from Acorda, Biogen Idec, Genentech, Genzyme/sanofi-aventis, Novartis, and Roche. 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. Dr. Comi has received personal compensation for activities with Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., Merck Serono, and Bayer Schering. Dr. Confavreux 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. Confavreux has received research support from Bayer Schering, Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis Pharmaceuticals, Inc., and Teva Neuroscience. Dr. Freedman has received personal compensation for activities with Bayer, Biogen Idec, Teva, Merck Serono, Novartis, Sanofi, and Celgene. Dr. Freedman9s institution has received research support from Bayer Healthcare and Genzyme. Dr. Olsson has received personal compensation for activities with Biogen Idec, Merck & Co., Inc., Sanofi-Aventis Pharmaceuticals, Inc., Novartis, and Bayer. Dr. Olsson has received research support from Biogen Idec, Merck & Co., Inc., Sanofi-Aventis Pharmaceuticals, Inc., Novartis, and Bayer. Dr. Wolinsky has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Genzyme Corporation, Hoffman LaRoche, Janssen Pharmaceutical, Novartis, Sanofi-Aventis Pharmaceuticals and Teva/Teva Neuroscience as a consultant. Dr. Wolinsky has received (royalty or license fee or contractual rights) payments from University of Texas. Dr. Wolinsky has received research support from Clayton Foundation for Research and the National Institutes of Health. Dr. Bagulho has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc. as an employee. Dr. Delhay has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc. Dr. Zheng has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc. as an employee. Dr. Truffinet has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc. 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.