FDA Approves Ponesimod for Relapsing-Remitting Multiple Sclerosis

September 2022

The approval of ponesimod was based on the results of a phase 3, head-to-head superiority trial for ponesimod versus teriflunomide for relapsing-remitting multiple sclerosis (MS), the Oral Ponesimod Versus Teriflunomide in Relapsing Multiple Sclerosis (OPTIMUM) trial.

“MS is a complex disease, and any individual’s response to MS disease-modifying therapy can vary,” said Bruce Bebo, PhD, Executive Vice President of Research at the National Multiple Sclerosis Society, in a news release from Janssen. “It’s so important that people living with MS have access to effective treatment options. We are pleased that there is a new therapy approved for relapsing MS.”

Ponesimod is a modulator of sphingosine-1-phosphate receptor 1 that reduces blood lymphocyte counts. In the recent phase 3 randomized clinical trial, OPTIMUM investigators compared the safety, tolerability, and efficacy of ponesimod with teriflunomide, an oral pyrimidine synthesis inhibitor that is approved for treating MS.

Patients in the study were adults aged 18 to 55 years with relapsing MS. More than 97% of patients had relapsing-remitting MS. The primary end point was the annualized relapse rate. Secondary end points were the change in symptoms associated with fatigue, the number of new lesions, and time to 12-week and 24-week disability accumulation.

A total of 1133 patients were randomized to receive oral ponesimod or teriflunomide. For the primary outcome, the annualized relapse rate in the ponesimod group was 30.5% lower than in the teriflunomide group (P <.001).

Several secondary outcomes also favored ponesimod. Symptoms associated with fatigue from baseline to week 108 were significantly reduced in the ponesimod group compared with the teriflunomide group (P = .002). In addition, the number of new lesions per year by week 108 was 56% lower in patients taking ponesimod compared with teriflunomide (P <.001). However, the risks for 12-week and 24-week disability accumulation were not different between groups, which the investigators suggested was likely because of a low level of baseline disability.

The proportion of patients with treatment-emergent adverse events or serious adverse events was similar between treatments groups. Adverse events caused treatment discontinuation more often in the ponesimod group (8.7%) than in the teriflunomide group (6.0%). Adverse events that were more common in the ponesimod group than in the teriflunomide group were pulmonary events (8.0% vs 2.7%) and hepatobiliary disorder or liver enzyme abnormality (22.7% vs 12.2%, 1 day after treatment ended, and 25.7% vs 14.5%, 15 days after treatment ended).

OPTIMUM investigators concluded that their results showed that ponesimod was superior to teriflunomide and was safe and well-tolerated.

In the news release, Janssen said that ponesimod is eliminated from the blood within 1 week and its effects on immune suppression cease within 2 weeks of discontinuation. The short half-life will allow patients to rapidly restore the immune system when needed.

“Every person with multiple sclerosis is affected differently, given variability in both the underlying disease and emerging symptoms. Continued innovation in this space is critical,” said Mathai Mammen, MD, PhD, Global Head of Janssen Research & Development, in the company’s news release.


Janssen Pharmaceutical Companies. Janssen announces U.S. FDA approval of PONVORY (ponesimod), an oral treatment for adults with relapsing multiple sclerosis proven superior to Aubagio (teriflunomide) in reducing annual relapses and brain lesions. News release. Published March 19, 2021. www.jnj.com/janssen-announces-u-s-fda-approval-of-ponvory-ponesimod-an-oral-treatment-for-adults-with-relapsing-multiple-sclerosis-proven-superior-to-aubagio-teriflunomide-in-reducing-annual-relapses-and-brain-lesions. Accessed January 15, 2022.

Kappos L, Fox RJ, Burcklen M, et al. Ponesimod compared with teriflunomide in patients with relapsing multiple sclerosis in the active-comparator phase 3 OPTIMUM study: a randomized clinical trial. JAMA Neurol. 2021;78:558-567.

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