Ponesimod Demonstrated Increased Clinical Benefit over Teriflunomide in Early Disease Subgroup Compared with Overall Population

Background: OPTIMUM, a Phase III, randomized, double-blind study, demonstrated superiority of ponesimod over teriflunomide on Annualized Relapse Rate (ARR) with Rate Ratio (RR)= 0.695 [99% CLs: 0.536, 0.902], number of Combined Unique Active Lesions (CUALs) with RR= 0.444 [95% CLs: 0.364, 0.542] and MS-fatigue with Mean Diff (MD) = -3.57 [95% CLs: -5.83, -1.32]. It is well established that early treatment in Multiple sclerosis (MS) with higher-potency therapies improve long-term outcomes.

Objectives: Our primary objective was to test whether a patient population with early disease has a differential benefit with ponesimod compared with teriflunomide.

Methods: In the OPTIMUM study, baseline Expanded Disability Status Scale (EDSS) scores were between 0-5.5. This subgroup analysis examined patients with EDSS ≤3 and/or who were treatment naïve. Treatment differences on ARR, CUALs and MS-fatigue in these subgroups were compared with the overall population.

Results: In the EDSS ≤3 subgroup, ponesimod reduced ARR by 47%, RR= 0.530 [99% CLs: 0.372, 0.755] and MS-fatigue MD improved to -4.31 [95% CLs: -6.99, -1.63] in favor of ponesimod. Treatment naïve patients also benefited from ponesimod compared with teriflunomide in terms of ARR and MS-fatigue. Changes in MS-fatigue in EDSS ≤3 and treatment naïve subgroup were further increased in favor of ponesimod, MD= -5.30 [95% CLs: -8.25, -2.35]. Results of this subgroup analysis were consistent with the overall population on CUALs.

Conclusions: Ponesimod demonstrated increased clinical benefit as compared with teriflunomide in early disease subgroups and compared with the overall population. This subgroup analysis confirms the advantage of using ponesimod as an early high efficacy treatment.