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

Kappos, Ludwig ; Burcklen, Michel; D'Ambrosio, Daniele; Fox, Robert J.; Freedman, Mark S.; Havrdova, Eva Kubala; Hennessy, Brian; Hohlfeld, Reinhard ; Larbalestier, Anna; Lemle, Alexandre; Lindenstrøm, Ewa; Lublin, Fred; Montalban, Xavier; Sidorenko, Tatiana; Sprenger, Till; Vaclavkova, Andrea; Wuerfel, Jens und Pozzilli, Carlo (2025): Ponesimod as add-on treatment in patients with active relapsing multiple sclerosis under dimethyl fumarate (POINT): A phase 3, randomized, placebo-controlled clinical trial. In: Multiple Sclerosis and Related Disorders, Bd. 102, 106616

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2211-0348
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198