OPTIMUM trial: Ponesimod superior to teriflunomide for relapsing MS

Patients who received ponesimod for relapsing MS saw a greater reduction in the annualized relapse rate compared with patients who received teriflunomide, according to results from a randomized clinical trial published in JAMA Neurology.

“Despite significant progress in MS therapy, there is still an unmet need for effective, safe and convenient treatments that can be used early in the disease course,” Ludwig Kappos, MD, chair of neurology at the University Hospital Basel in Switzerland, and colleagues wrote. “Given the number of alternative options of oral treatments, head-to-head comparative trials to inform choices are still lacking.”

In the OPTIMUM phase 3 trial, researchers compared 1,133 patients (median age 37 years, 64.9% women) with relapsing MS who were randomly assigned to receive either 20 mg ponesimod (n = 567 patients) — marketed in the United States as Ponvory (Janssen) — or 14 mg teriflunomide (n = 566 patients), which is sold under the brand name Aubagio (Sanofi Aventis) in addition to generic formulations. The primary endpoint was the annualized relapse rate (ARR); the secondary endpoints included changes in Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS), the number of combined active lesions, time to 12-week confirmed disability accumulation and time to 24-week confirmed disability accumulation.

After 108 weeks, the researchers reported 242 confirmed relapses in the ponesimod cohort vs. 344 confirmed relapses in the teriflunomide cohort. Ponesimod reduced the ARR by 30.5% (0.202 vs. 0.29, respectively; P < .001). The mean difference in FSIQ-RMS was –3.57 (–0.01 vs. 3.56; P < .001), the reduction in active lesions per year was 56% (1.405 vs. 3.164; P < .001), and the reduction in 12-week and 24-week confirmed disability accumulation risk estimates was 17% (10.1% vs. 12.4%; P = .29) and 16% (8.1% vs. 9.9%; P = .37), respectively. Additionally, the ponesimod cohort had lower brain volume loss (–0.91% vs. –1.25%; P < .001).

“Ponesimod is superior to teriflunomide, an approved oral disease-modifying therapy (DMT), on the primary endpoint, ARR, and also on two of three secondary endpoints: MRI activity and fatigue, a most debilitating MS symptom that until now appears not to have been shown in a prospective phase 3 study to be effectively addressed by other DMTs,” Kappos and colleagues concluded. “Ponesimod was well tolerated, and the safety results were in line with previous observations in its phase 2 dose-finding study and findings on other S1P receptor modulators in controlled studies.”