Teriflunomide Shows Consistent Clinical Efficacy on Severe Relapses across Two Phase 3 Trials in Patients with Relapsing forms of Multiple Sclerosis, TEMSO and TOWER (P7.212)

OBJECTIVE: To report key efficacy, safety, and additional clinically relevant analyses from the TEMSO (NCT00134563) and TOWER (NCT00751881) BACKGROUND: is a once-daily oral immunomodulator approved for relapsing-remitting MS. DESIGN/METHODS: In TEMSO/TOWER, 1088/1169 patients with relapsing forms of MS were randomized (1:1:1) to oral once-daily teriflunomide 14 mg or 7 mg, or placebo. Treatment duration was 108 weeks (TEMSO) or variable (TOWER; 48-152 weeks, ending 48 weeks after last patient randomized). Primary and key secondary endpoints were annualized relapse rate (ARR) and disability progression confirmed for 12 weeks. Additional endpoints included magnetic resonance imaging measures (TEMSO), safety, and tolerability. Post hoc analyses examined the effect of teriflunomide on 5 severe relapse outcomes: (A) relapses with sequelae defined by increase in Expanded Disability Status Scale score/Functional Score 30 days post relapse; (B) relapses with investigator-defined sequelae; (C) severe relapses by Panitch definition; (D) relapses leading to hospitalization; and (E) relapses requiring intravenous corticosteroid treatment. RESULTS: In TEMSO/TOWER, teriflunomide 14 mg significantly reduced both ARR and disability progression vs placebo; teriflunomide 7 mg significantly reduced ARR. Teriflunomide 14 mg significantly reduced annualized rates of severe relapse outcomes compared with placebo in TEMSO/TOWER by: (A) 36.2[percnt] ( P =0.0011)/36.6[percnt] ( P =0.0021); (B) 52.6[percnt] ( P P =0.0004); (C) 38.5[percnt] ( P =0.0286)/52.5[percnt] ( P =0.0015); (D) 59.3[percnt] ( P P =0.0155); and (E) 33.7[percnt] ( P =0.0003)/35.7[percnt] ( P =0.0002). Teriflunomide 7 mg also reduced annualized rates of severe relapses, although not significantly, in all definitions. Both teriflunomide doses showed similar and manageable safety profiles across the 2 CONCLUSIONS: has shown consistent and significant efficacy on ARR and disability progression (14 mg) in 2 phase 3 studies. Teriflunomide also reduces severe relapses as measured by several relapse outcome parameters. This may reduce relapse-related healthcare costs and increase patients’ quality of life. Study Supported by: a Sanofi company. Disclosure: Dr. Macdonell has received personal compensation for activities with Bayer Schering. Dr. Stangel has received personal compensation for activities with Bayer HealthCare. Dr. Maurer has received personal compensation for activities with Bayer HealthCare. Dr. Dukovic has received personal compensation for activities with Sanofi. Dr. Truffinet has received personal compensation for activities with Genzyme Corporation as an employee. Dr. Bozzi has received personal compensation for activities with Sanofi as an employee. Dr. Dive-Pouletty has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc. Dr. Freedman has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Chugai Pharmaceutical Co., Ltd, EMD Serono, Genzyme, Novartis, Sanofi, and Teva.