TOPIC: Efficacy and Safety of Once-Daily Oral Teriflunomide in Patients with First Clinical Episode Consistent With Multiple Sclerosis (PL2.002)

Abstract

OBJECTIVE: The phase 3 TOPIC study (NCT00622700) assessed the efficacy and safety of teriflunomide in patients with a first clinical episode consistent with multiple sclerosis (MS) and 蠅2 T2 lesions on MRI scan. BACKGROUND: Teriflunomide is an oral once-daily immunomodulator for relapsing-remitting forms of MS. Pivotal studies of teriflunomide in relapsing forms of MS (RMS; TEMSO:NCT00134563; TOWER:NCT00751881) showed consistent efficacy across key clinical and MRI (TEMSO only) measures, and a well-characterized safety profile. DESIGN/METHODS: TOPIC was a double-blind, placebo-controlled, parallel-group study. Patients were randomized to teriflunomide 14mg, teriflunomide 7mg, or placebo. The primary endpoint analysis was time to new clinical relapse (108-week probability of new clinical relapse also calculated), and the key secondary endpoint analysis was time to new clinical relapse or MRI lesion. Safety and tolerability were also assessed. RESULTS: Baseline characteristics were generally well balanced. Of the randomized population (n=618), 59.1% had monofocal lesion presentation and 31.4% had 蠅1 gadolinium-enhancing lesion. Median time since neurological event was 2 months. Compared with placebo, teriflunomide 14mg reduced risk of new clinical relapse by 42.6% (p=0.0087), and 108-week probability of new clinical relapse was 24.0% vs 35.9% for placebo. Teriflunomide 14mg also reduced risk of new clinical relapse or MRI lesion by 34.9% (p=0.0003). Teriflunomide 7mg reduced risk of new clinical relapse by 37.2% (p=0.0271) and risk of new clinical relapse or MRI lesion by 31.4% (p=0.0020). Occurrence of adverse events (AEs) was similar across groups and consistent with previous studies. AEs more common with teriflunomide included alanine aminotransferase increase, diarrhea, hair thinning, infection (urinary and respiratory tract), and paresthesia. CONCLUSIONS: Teriflunomide demonstrated efficacy in delaying a new clinical relapse in patients with a first clinical episode consistent with MS. Together with outcomes from TEMSO and TOWER, these findings support the beneficial effect of teriflunomide in patients with RMS early and later in their disease course, and across a range of disease activity. Study Supported by: Genzyme, a Sanofi company

Disclosure: Dr. Miller has received personal compensation for activities wtih Acorda Therapeutics, Biogen Idec, GlaxoSmithKline, Inc., Merck Serono, Novartis, Nuron Biotech, Ono Pharmaceutical, Genzyme/Sanofi, Questcor, and Accordant Health Services. Dr. Miller has received personal compensation in an editorial capacity for Continuum and Continuum Audio. Dr. Miller has received research support from Acorda, Biogen Idec, Genentech, Inc., Genzyme/Sanofi-Aventis, Novartis, Osmotica, and Roche. Dr. Wolinsky has received personal compensation for activities with Teva Neuroscience, Sanofi-Aventis Pharmaceuticals Inc., Roche Diagnostics Corp., Novartis, XenoPort, RND, Genzyme Corp., and Athersys. Dr. Wolinsky has received royalty payments from the University of Texas. Dr. Wolinsky has received research support from National Institutes of Health, Sanofi-Aventis Pharmaceuticals Inc., and Genzyme Corp. Dr. Kappos has received personal compensation for activities with the University Hospital Basel. Dr. Kappos has received research support from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, Novartis, and Roche Diagnostics Corp. Dr. Comi has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., Novartis, Merck Serono, Biogen Idec, Bayer Pharmaceuticals Corp., Teva Neuroscience, and Actellion. Dr. Freedman has received personal compensation for activities with Actelion, Bayer, Biogen Idec, EMD Canada, Genzyme Corporation, Novartis, Opexa, Teva Neuroscience, and Sanofi-Aventis Pharmaceuticals, Inc. Dr. Freedman has received research support from Bayer and Genzyme. Dr. Olsson has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals Inc., Merck Serono, and Biogen Idec. Dr. Olsson has received research support from Sanofi-Aventis Pharmaceuticals Inc., Merck Serono, and Biogen Idec. Dr. Liang has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc. as an employee. Dr. Bauer has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc. as an employee. Dr. Benamor has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc. as an employee. Dr. Wamil 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. as an employee. Dr. O'Connor has received personal compensation for activities with Teva Neuroscience, Sanofi-Aventis Pharmaceuticals Inc., Roche Diagnostics Corp., Novartis, Genentech Inc., EMD Serono, Biogen Idec, Bayer Pharmaceuticals Corp., Actelion, and Genzyme Corp. Dr. O'Connor has received research support from Teva Neuroscience, Sanofi-Aventis Pharmaceuticals Inc., Roche Diagnostics Corp., Novartis, Genmab, Genentech Inc., EMD Serono, Daiichi Pharmaceutical Corp., Cognosci, BioMS, Biogen Idec, Bayer Pharmaceuticals Corp., and Actelion.