12-Year Clinical Efficacy and Safety Data for Teriflunomide: Results from a Phase 2 Extension Study (P7.223)

OBJECTIVE: To report long-term efficacy and safety data from patients treated with teriflunomide for ≤12 years. BACKGROUND: Teriflunomide is a once-daily oral immunomodulator for the treatment of relapsing-remitting MS. In phase 2 and 3 studies, teriflunomide demonstrated consistent efficacy with positive effects on relapse rates, risk of disability progression, and magnetic resonance imaging outcomes, with a manageable safety and tolerability profile. DESIGN/METHODS: In the core phase 2 study (NCT01487096), patients with relapsing MS (18-65 years; Expanded Disability Status Scale [EDSS] score ≤6; 蠅2 clinical relapses during the previous 3 years and 1 relapse in preceding year) were randomized (1:1:1) to teriflunomide 14mg or 7mg, or placebo. After completing the 36-week core study, patients could enter the long-term open-label extension (NCT00228163). In the extension, patients continued teriflunomide therapy and those previously treated with placebo were reallocated (1:1) to teriflunomide 14mg or 7mg. EDSS score was assessed every 24 weeks, and clinical relapses and safety reported throughout the study. RESULTS: Of 179 patients originally randomized, 147 entered the extension. Including treatment in core and extension studies, patients received teriflunomide for ≤576 weeks, with a cumulative duration of teriflunomide exposure of >990 patient-years (both treatment groups). During the study, annualized relapse rates remained low (both groups), and percentage of patients free from relapse during the extension was greater in the 14-mg (51.5[percnt]) versus the 7-mg group (39.5[percnt]). Patients had minimal increases in EDSS score following up to 528 weeks of treatment. No new/unexpected adverse events were identified following long-term teriflunomide treatment, and the safety and tolerability profile was consistent with other clinical studies. CONCLUSIONS: Relapse rates and change in EDSS score remained low in both groups following up to 12 years of teriflunomide treatment. No unexpected safety findings were associated with long-term teriflunomide treatment. Study Supported by: Genzyme, a Sanofi company. Disclosure: Dr. Kremenchutzky has received personal compensation for activities with Biogen Idec, Sanofi, Genzyme, Novartis, Bayer Pharmaceuticals Corp., Teva Neuroscience, and EMD Serono as a consultant. Dr. Kremenchutzky has received research support from Biogen Id Dr. Freedman has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Chugai Pharmaceutical Co., Ltd, EMD Serono, Genzyme, Novartis, Sanofi, and Teva. Teva Neuroscience, Dr. Dukovic has received personal compensation for activities with Sanofi. Dr. Benamor has received personal compensation for activities with Sanofi as an employee. Dr. Truffinet has received personal compensation for activities with Genzyme Corporation as an employee. D. O9Connor has received personal compensation for activities with Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Roche Diagnostics Corporation, Novartis, Genentech, EMD Serono, Biogen Idec, Bayer Pharmaceuticals Corporation, Actelion, and Genzyme.