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Ponesimod Shows Sustained Efficacy and Safety in RMS Over 5 Years

Key Takeaway
Consider ponesimod for sustained RMS control with a favorable long-term safety profile.

This long-term extension (LTE) study of the phase 3 OPTIMUM trial evaluated the safety and efficacy of ponesimod 20 mg in 877 participants with relapsing multiple sclerosis (RMS) over 240 weeks. Participants either continued ponesimod (P20 mg/P20 mg) or switched from teriflunomide to ponesimod (T14 mg/P20 mg). The primary endpoint, annualized relapse rate (ARR), was 0.143 (95% CI: 0.123-0.167) for the continuous ponesimod group compared to 0.184 (95% CI: 0.158-0.213) for the switch group. Secondary endpoints showed that 17.5% of the P20 mg/P20 mg group achieved no evidence of disease activity (NEDA)-3, versus 7.5% in the T14 mg/P20 mg group. Safety assessments revealed that 93.6% of participants experienced at least one treatment-emergent adverse event (TEAE), with serious TEAEs in 12.9% and discontinuations due to TEAEs in 8.6% of participants. The study concluded that ponesimod's effects on disease control are sustained over 5 years with no new safety concerns, supporting its long-term use in RMS management.

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INTRODUCTION: In phase 3 OPTIMUM study, ponesimod demonstrated superior efficacy and acceptable safety vs teriflunomide in participants with relapsing multiple sclerosis (RMS). This long-term extension (LTE) study was designed to assess the safety and efficacy of ponesimod 20 mg (P20 mg) during extended treatment. METHODS: Participants who completed core OPTIMUM study entered OPTIMUM-LTE; Participants receiving P20 mg once daily (OD) in core continued with the same dose (P20 mg/P20 mg) and those receiving teriflunomide 14 mg OD switched to P20 mg (T14 mg/P20 mg) in the LTE study. Safety assessments included treatment-emergent adverse events (TEAE). Efficacy was assessed using annualized relapse rate (ARR), time to first confirmed relapse up to end of study (EOS), confirmed disability accumulation (CDA), and magnetic resonance imaging (MRI)-based endpoints. RESULTS: Of 1133 participants from core study, 877 were enrolled in 240-week LTE study (ponesimod: 439; teriflunomide:438). During LTE, 93.6% of participants in both groups experienced ≥ 1 TEAE; overall, serious TEAEs were experienced by 12.9% of participants (P20 mg/P20 mg: 12.8%; T14 mg/P20 mg: 13.0%) and TEAEs leading to study treatment discontinuation were experienced by 8.6% of participants (P20 mg/P20 mg: 7.7%; T14 mg/P20 mg: 9.4). In combined analysis period, mean ARR was 0.143 (95% CL: 0.123-0.167) for P20 mg/P20 mg and 0.184 (95% CL: 0.158-0.213) for T14 mg/P20 mg; 44.3% of participants in P20 mg/P20 mg and 49.5% in T14 mg/P20 mg experienced relapse. Overall, more participants in P20 mg/P20 mg vs T14 mg/P20 mg group achieved no evidence of disease activity (NEDA)-3 at end of LTE (17.5% vs 7.5%). CONCLUSIONS: Ponesimod demonstrated extended safety and sustained efficacy over 5 years in participants with RMS, without new safety signals. Results suggest that the effects on the MS disease control are maintained with ponesimod over the LTE treatment period.
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