TERIFLUNOMIDE SHOWS CONSISTENT CLINICAL EFFICACY ON SEVERE RELAPSES ACROSS TEMSO AND TOWER- 2 PHASE 3 TRIALS
Author(s)
Leist TP1, Stangel M2, Macdonell R3, Mäurer M4, Thangavelu K5, Truffinet P6, Bozzi S7, Dive-Pouletty C6, Freedman MS8
1Thomas Jefferson University Hospital, Philadelphia, PA, USA, 2Medizinische Hochschule Hannover, Hannover, Germany, 3Austin Health, Heidelberg, Australia, 4Caritas Krankenhaus Bad Mergentheim, Bad Mergentheim, Germany, 5Genzyme, a Sanofi company, Cambridge, MA, USA, 6Genzyme, a Sanofi company, Chilly-Mazarin, France, 7Sanofi, Chilly-Mazarin, France, 8University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, ON, Canada
OBJECTIVES: Teriflunomide is a once-daily oral immunomodulator approved for relapsing-remitting MS. Here we report the key efficacy, safety, and post hoc analyses from the randomized, placebo-controlled phase 3 trials TEMSO (NCT00134563) and TOWER (NCT00751881). METHODS: In TEMSO/TOWER, a total of 1088/1169 patients with relapsing MS were randomized (1:1:1) to once-daily teriflunomide 14 mg, teriflunomide 7 mg, or placebo. Treatment duration was 108 weeks (TEMSO) or variable, based on time of enrollment (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 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 postrelapse; (B) relapses with investigator-defined sequelae; (C) severe relapses by Panitch definition; (D) relapses leading to hospitalization; and (E) relapses requiring treatment with intravenous corticosteroids. RESULTS: In TEMSO/TOWER, teriflunomide 14 mg significantly reduced both ARR and disability progression vs placebo. Teriflunomide 7 mg significantly reduced ARR but not disability progression. Teriflunomide 14 mg significantly reduced annualized rates of severe relapse outcomes compared with placebo in TEMSO/TOWER by: (A) 36.2% (P=0.0011)/36.6% (P=0.0021); (B) 52.6% (P<0.0001)/53.5% (P=0.0004); (C) 38.5% (P=0.0286)/52.5% (P=0.0015); (D) 59.3% (P<0.0001)/33.6% (P=0.0155); and (E) 33.7% (P=0.0003)/35.7% (P=0.0002). Teriflunomide 7 mg also reduced annualized rates of severe relapses, although not significantly in all definitions. Both teriflunomide doses showed similar safety profiles across the 2 studies. CONCLUSIONS: Teriflunomide 14 mg has shown consistent and significant positive effects on ARR and disability progression in 2 phase 3 studies. Teriflunomide also reduces severe relapses as measured by various relapse definitions, which may reduce relapse-related healthcare costs and improve patients’ quality of life.
Conference/Value in Health Info
2015-05, ISPOR 2015, Philadelphia, PA, USA
Value in Health, Vol. 18, No. 3 (May 2015)
Code
PND11
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Neurological Disorders