Phase III OPTIMUM study of ponesimod shows efficacy in multiple sclerosis

The Janssen Pharmaceutical Companies of Johnson & Johnson announced the results from the Phase III OPTIMUM study for ponesimod, an investigational selective S1P1 receptor modulator, showing superior efficacy on the primary endpoint and most secondary endpoints compared to Aubagio (teriflunomide) 14 mg in adults with relapsing multiple sclerosis (MS). In the head-to-head, two-year Phase III comparative study, statistically significant reduction of annualized relapse rate (ARR), the study's primary endpoint, was observed with ponesimod when compared to teriflunomide by 30.5% up to week 108 (ARR = 0.202 for ponesimod 20 mg vs. 0.290 for teriflunomide 14 mg).

Several pre-specified secondary endpoints were also examined as part of the OPTIMUM trial, including fatigue. Based on results from the Fatigue Symptoms and Impacts Questionnaire - Relapsing Multiple Sclerosis (FSIQ-RMS) at week 108, statistically significant effects on fatigue symptoms were observed with ponesimod compared to teriflunomide (mean difference: -3.57, p=0.0019). FSIQ-RMS is a new MS-specific, 20-item patient-reported outcome measure that comprises symptoms and impacts with an increase from baseline indicating worsening in fatigue symptoms. Additional secondary endpoints of note include cumulative number of combined unique active lesions (CUALs) using magnetic resonance imaging (MRI), time to first 12-week confirmed disability accumulation (CDA) and time to first 24-week CDA from baseline. A 56% reduction in the number of CUALs was observed with ponesimod compared to teriflunomide. The 12-week CDA was observed in 10.1% and 12.4% of patients in the ponesimod and teriflunomide arms, respectively; however, the result was not statistically significant. The safety profile observed for ponesimod in the OPTIMUM study was consistent with previous studies of ponesimod and the known safety profile for other S1P receptor modulators.

The data were presented by Professor Ludwig Kappos, Chair of the Department of Neurology at University Hospital of Basel, Switzerland, on behalf of the study's investigators, as part of an oral presentation at the 35th Congress of The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).