Ponesimod as add-on treatment in patients with active relapsing multiple sclerosis under dimethyl fumarate (POINT): A phase 3, randomized, placebo-controlled clinical trial.

BACKGROUND

Combining two oral therapies with different mechanisms could be an attractive treatment strategy for multiple sclerosis (MS) to increase efficacy; however, evidence of such efficacy and safety is lacking.

OBJECTIVES

The phase 3 randomized, double-blind, placebo-controlled POINT study evaluated efficacy and safety of ponesimod 20 mg versus placebo as an add-on therapy to ongoing dimethyl fumarate (DMF) treatment in patients with active relapsing MS despite DMF monotherapy.

METHODS

Patients (18-55 years) were randomized (1:1) to ponesimod+DMF or placebo+DMF orally once-daily for ≤156 weeks. Primary endpoint was annualized relapse rate (ARR) at end-of-study (EOS). Secondary endpoints were 12-week confirmed disability accumulation (CDA), time-to-first confirmed relapse, and number of combined unique active lesions (CUALs) on brain Magnetic resonance imaging (MRI) at EOS.

RESULTS

The study was prematurely terminated due to slow recruitment; of 600 planned patients, 136 (23 %; [ponesimod: n = 68, placebo: n = 68]) were randomized. Primary endpoint (ARR) was not met (rate ratio, ponesimod+DMF versus placebo+DMF: 1.2; p = 0.5252). Ponesimod+DMF group showed a lower mean number of CUALs/year (rate ratio: 0.37; p = 0.0072). Other efficacy outcomes did not differ between the treatment groups. Adverse events (AEs) were comparable between groups (ponesimod+DMF: 48 [71.6 %]; placebo+DMF: 53 [77.9 %]); dizziness was the most commonly reported AE in the ponesimod+DMF group (10.4 %).

CONCLUSIONS

This terminated study did not demonstrate the superiority of ponesimod+DMF on clinical efficacy endpoints. In the exploratory analysis ponesimod+DMF versus DMF alone appeared associated with a lower disease activity as assessed by MRI. No new safety signals were reported for ponesimod+DMF.

GOV IDENTIFIER: NCT02907177 URL: https://clinicaltrials.gov/study/NCT02907177.