Objectives: To report efficacy and safety from TEMSO and TOWER.
Methods: In TEMSO/TOWER, 1088/1169 patients with RMS (18–55 years; Expanded Disability Status Scale [EDSS] score ≤5.5 at screening; ≥1 or ≥2 relapses in the 12 or 24 months before randomization, respectively) were randomized to once-daily placebo (PBO), or teriflunomide 7 mg or 14 mg. Treatment duration was 108 weeks (TEMSO) or variable (TOWER; 48–152 weeks ending 48 weeks after last patient randomized). The primary and key secondary endpoints were annualized relapse rate (ARR) and sustained disability progression (confirmed for 12 weeks). Additional endpoints included MRI (TEMSO only), and safety and tolerability.
Results: Teriflunomide 14 mg reduced ARR by 31.5%/36.3% (TEMSO/TOWER; p<0.001) and disability progression by 29.8%/31.5% (p=0.028/p=0.044), versus PBO. Teriflunomide 7 mg reduced ARR by 31.2%/22.3% (p<0.001/p=0.02) versus PBO, but did not significantly reduce disability progression. In TEMSO, both teriflunomide doses were superior to PBO on a range of MRI endpoints, with evidence of a dose effect favoring 14 mg. Cumulative drug exposure in the teriflunomide 14 mg group was 614.2/576.2 patient years (TEMSO/TOWER). Teriflunomide was generally well tolerated in both studies. The most frequently reported treatment-emergent adverse events more common with teriflunomide than PBO were alanine aminotransferase increase, hair thinning, and diarrhea. There were no deaths reported in TEMSO and 4 in TOWER (teriflunomide 7 mg: motor vehicle accident; teriflunomide 14 mg: sepsis, suicide; PBO: respiratory infection), with no evidence that teriflunomide was a causative factor.
Conclusions: In both TEMSO and TOWER teriflunomide 14 mg significantly reduced ARR and disability progression versus PBO. MRI disease activity was also significantly reduced with teriflunomide in TEMSO. Teriflunomide was generally well tolerated with a well-characterized safety profile.
Study supported by Genzyme, a Sanofi company.