Long-term safety and efficacy of ponesimod, an oral S1P1 receptor modulator, in relapsing-remitting multiple…

Randomized trialMultiple sclerosis and related disorders· Jul 2026

Long-term safety and efficacy of ponesimod, an oral S1P1 receptor modulator, in relapsing-remitting multiple sclerosis (RRMS): Results from randomized phase 2b core and extension studies spanning up to 13 years.

Tomas Olsson, Xavier Montalban, Reinhard Hohlfeld … Ludwig Kappos

Multiple Sclerosis & NeuroimmunologyRandomized trialTreatmentQ2IF 2.8

Long-term ponesimod treatment associated with low relapse rates in relapsing-remitting multiple sclerosis

Long-term safety and efficacy of ponesimod, an oral S1P1 receptor modulator, in relapsing-remitting multiple sclerosis (RRMS): Results from randomized phase 2b core and extension studies spanning up to 13 years.

Tomas Olsson … Ludwig Kappos

Multiple sclerosis and related disorders · Jul 2026 · Q2 in Neurology

Background

Ponesimod demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (relapsing-remitting multiple sclerosis) in 24-week phase-2 core study, further confirmed by an interim combined analysis of the core and open-label long-term extension (long-term extension) studies (NCT01093326; up to 8 years).

Methods

In TP2 (TP2 and TP3 combined duration: ∼10.4 years), participants on 40 mg were re-randomized (1:1) to 10/20 mg, while others continued same dose; in TP3 all participants received 20 mg.

n = 393 participants

Results

relapse risk stayed low with long-term ponesimod

ARR 0.14 (95% CI 0.10 to 0.20)

CI excludes the null - significant

More results

For 20 mg dose, total 92.4% participants experienced ≥1 TEAEs (73.1% mild/moderate severity) and 19 (13%) participants discontinued study.

Mean [SD] T1 Gd+ lesions decreased from ponesimod baseline (2.62 [7.06]) to 12.4 years (0.26 [1.48]), mean (95% CI) CUALs per participant/year=3.97 (2.75-5.73).

“

Conclusion

Ponesimod treatment for up to 13 years was not associated with new safety concerns. Participants continued to experience low levels of disease activity consistently across clinical and MRI outcomes.

Long-term safety and efficacy of ponesimod, an oral S1P1 receptor modulator, in relapsing-remitting multiple sclerosis (RRMS): Results from randomized phase 2b core and extension studies spanning up to 13 years.

Long-term safety and efficacy of ponesimod, an oral S1P1 receptor modulator, in relapsing-remitting multiple sclerosis (RRMS): Results from randomized phase 2b core and extension studies spanning up to 13 years.

Related papers