Teriflunomide Increases the Proportion of Patients Free from Disease Activity in the TEMSO Phase III Study (PD5.007)

Abstract

Objective: To determine the effect of teriflunomide in reducing the risk of a composite endpoint of disease activity in patients with relapsing forms of MS (RMS) over a 2-year period in TEMSO (NCT00134563). Background Teriflunomide is a novel oral disease-modifying therapy in development for the treatment of RMS. Teriflunomide reduced the annualized relapse rate, the risk of 12-week confirmed disability progression and MRI activity in a dose-dependent fashion in TEMSO. Design/Methods: TEMSO randomized 1088 RMS patients (mean age: 38 years; mean Expanded Disability Status Scale [EDSS] score: ≤5.5; mean number of relapses within past 2 years: 2.2) to placebo (N=363), teriflunomide, 7 mg (N=366) or 14 mg (N=359), once-daily for 108 weeks. This post hoc analysis evaluated time to disease activity (clinical relapse, 12-week sustained disability progression, or new unique active lesions (new T1 gadolinium-enhancing and new/enlarged T2 lesions) using a log-rank test with treatment group as the test variable and region and baseline EDSS strata as stratification factors. Hazard ratios for teriflunomide versus placebo were estimated using a Cox regression model. Results: Both teriflunomide doses reduced the risk of disease activity compared with placebo (p=0.0002 and p=0.0293, for 14 mg and 7 mg respectively). A total of 82 [22.9%], 67 [18.4%] and 52 [14.3%] patients remained disease free for teriflunomide 14 mg, 7 mg and placebo, respectively. Hazard ratios (95% confidence intervals) were 0.726 (0.617, 0.855) for 14 mg and 0.834 (0.711, 0.978) for 7 mg versus placebo. The respective proportions of patients free from clinical disease were 189 (52.8%), 180 (49.3%) and 156 (43.0%), and from new MRI activity were 144 (40.2%), 117 (32.1%) and 89 (24.5%). Conclusions: Teriflunomide treatment led to nearly twice as many patients being free from all measured clinical and MRI disease activity, with a trend, as in the core study, favoring the 14 mg dose. Supported by: sanofi-aventis. Disclosure: Dr. Freedman has received personal compensation for activities with Bayer Healthcare, Genzyme Corporation, EMD Serono, Novartis, Sanofi-Aventis Pharmaceuticals, Inc., and Teva Neuroscience. Dr. Freedman has received research support from Genzyme Corporation and Bayer Healthcare. 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. Wolinsky has received personal compensation for activities with Astellas, Bayer Pharmaceuticals Corporation, Bayer Multiple Sclerosis Council, Celgene Corporation, Eli Lilly & Company, Roche Diagnostics Corporation, Novartis, Sanofi-Aventis Pharmaceuticals and Teva Neuroscience as consultant and participant on monitoring and advisory boards. Dr. Wolinsky has received (royalty or license fee or contractual rights) payments from University of Texas Health Science Center at Houston. Dr. Wolinsky has received research support from Sanofi-Aventis Pharmaceuticals, Inc. 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. Comi has received personal compensation for activities with Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., Merck Serono, Bayer Schering, and Biogen Dompe. 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. Olsson has received personal compensation for activities with Biogen Idec, Merck & Co., Inc., Sanofi-Aventis Pharmaceuticals, Inc., Novartis, and Bayer Healthcare. Dr. Olsson has received research support from Biogen Idec, Merck & Co., Inc., Sanofi-Aventis Pharmaceuticals, Inc., Novartis and Bayer Healthcare. Dr. Truffinet has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc. Dr. Dukovic has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals as an employee. Dr. Miller has received personal compensation for activities with Acordia Therapeutics, Avanir, Biogen Idec, Chelsea Therapeutics, EMD Serono, GlaxoSmithKline, La-Ser, Merck Serono, Novartis, Nuron BiotechONO, Pfizer, Sanofi-Aventis, and Teva Neuroscience. Dr. Miller has received personal compensation in an editorial capacity for Continuum and Real Living with Multiple Sclerosis. Dr. Miller has received research support from Acorda, Biogen Idec, Genentech, Genzyme, Novartis, Roche, Sanofi-Aventis, and Teva Neuroscience.