OPTIMUM

OPTIMUM [101], was a 108 week multicenter, randomized, double-blind, parallel group, and active controlled study, evaluating the efficacy, safety, and tolerability of daily oral PNM 20 mg versus daily oral teriflunomide (TFM) 14 mg in adults with RRMS. OPTIMUM enrolled 1,133 patients, randomized to receive PNM (*n* = 567) or TFM (*n* = 566). Inclusion criteria included ages 18 to 55 years, EDSS 0.0-5.0, diagnosis of RRMS, and active disease in the 24 months prior to screening. The primary end-point was ARR over 108 weeks. Key secondary end-points included change from baseline to week 108 in fatigue-related symptoms, as measured by the symptoms domain of the FSIQ-RMS. Other secondary endpoints included the mean number of combined unique active lesions (CUAL) per year, defined as new Gd+1 lesions and any new or enlarging T2 lesions. In addition, time to 12-week and 24-week CDP was also determined.

There was a 30.5% relative reduction (*p* = 0.0003) in ARR in PNM treated patients (0.202 versus 0.290) compared to TFM treated patients. Ponesimod demonstrated superior improvement in fatigue scores at week 108 compared to TFM as measured by the FSIQ-RMS weekly symptom score (mean difference −3.57, *p* = 0.0019). There was a 56% relative reduction in CUALs per year (1.405 versus 3.164) in patients treated with PNM. No significant differences between PNM and TFM seen for 12-week or 24-week CDP.
