Annualized relapse rate reduction, fatigue, magnetic resonance imaging activity, brain volume loss, and no evidence of disease activity status were all superior in the ponesimod-treated group.
Ludwig Kappos, MD
Recently published data from the phase 3 OPTIMUM study (NCT02425644) revealed that treatment with ponesimod (Ponvory; Janssen Pharmaceutical) is superior to teriflunomide (Aubagio; Sanofi) across a number of outcomes excluding confirmed disability accumulation (CDA) in patients with multiple sclerosis (MS).1
The fully published data come less than a month after the FDA approved ponesimod for the treatment of adults with relapsing multiple sclerosis (MS).2 Led by Ludwig Kappos, MD, professor of neurology, University of Basel, the results of the study were scheduled to be presented at the American Academy of Neurology (AAN) 2020 Annual Meeting, which was canceled due to the COVID-19 pandemic.
Patients diagnosed with MS included in the study were randomized 1:1 to 20 mg of ponesimod or 14 mg of teriflunomide once daily and the placebo for 108 weeks, with a 14-day gradual up-titration of ponesimod starting at 2 mg and were assessed at a follow-up period of 30 days.1
Among a cohort of 1133 patients, ponesimod reduced annualized relapse rate (ARR) by 30.5% compared with teriflunomide (mean ARR, 0.202 vs 0.290; rate ratio [RR], 0.695 [99 confidence limits (CLs), 0.536-0.902]; P <.001). These results were consistent in the sensitivity analyses after adjusting for the presence of enhancing lesions.
Secondary end points such as the Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS), a validated patient-reported outcome measure, was lower for fatigue symptoms in the ponesimod group than the teriflunomide group at week 108. The least-square means were 0.01 vs 3.56 (mean difference, –3.57 [95% CLs, –5.83 to –1.32]; P = .002).
The cumulative number of combined unique active lesions (CUALs) per year on annual brain magnetic resonance imaging (MRI) were reduced by 56% with treatment of ponesimod compared with teriflunomide (1.405 vs 3.164; RR, 0.444 [95% CLs, 0.364–0.542]; P <.001).
Between the 2 groups, the risk of 12- and 24-week CDA did not differ. Exploratory outcomes such as brain volume loss was lower in the ponesimod group vs the teriflunomide group from baseline to week 108. The least-squares mean percentage was –0.91% vs –1.25% (mean difference, 0.34 percentage points [95% CL, 0.17-0.50]; exploratory P <.001).
Further exploratory end points were no evidence of disease activity (NEDA)-3 and NEDA-4 status from baseline. The estimated percentage for NEDA-3 from baseline to week 108 was 25% for the ponesimod group compared with 16.4% for teriflunomide. Notably, the odds ratio for achieving 2-year NEDA-3 was 1.70 (95% CLs, 1.27-2.28).
The presence of new or enlarging T2 lesions, occurring in 53.4% and 65.2% of ponesimod- and teriflunomide-treated patients, was the most frequent reason for not achieving NEDA-3. As for NEDA-4, the estimated percentage of patients achieving this measure from baseline to week 108 was 11.4% vs 6.5% in the ponesimod vs teriflunomide groups (odds ratio, 1.85 [95% CLs, 1.24–2.76]; P = .003).
Neither group differed in the proportion of patients who experienced at least 1 treatment-emergent adverse event (TEAE). The most common TEAEs, observed in more than 10% of patients, were an increased alanine aminotransferase (ALT) level, nasopharyngitis, headache, upper respiratory tract infection, and alopecia.