Janssen’s S1P receptor modulator ponesimod showed its superiority to teriflunomide on annualized relapse rates, fatigue symptoms, MRI activity, brain atrophy, and NEDA-3 in patients with relapsing multiple sclerosis.
Robert J. Fox, MD
Ponesimod (Janssen Pharmaceutical), an orally active, highly selective and reversible modulator of sphingosine-1 phosphate (S1P) receptor, has been shown to be superior to teriflunomide (Aubagio; Sanofi) in the treatment of relapsing multiple sclerosis (MS).1
The data, which were scheduled to be presented at the now-canceled American Academy of Neurology (AAN) 2020 Annual Meeting, suggest that ponesimod’s effect on annualized relapse rates (ARR), fatigue symptoms, magnetic resonance imaging (MRI) activity, brain atrophy, and no evidence of disease activity (NEDA) were superior to teriflunomide. Additionally, there were no significant differences between the treatments on 12-week and 24-week confirmed disability accumulation estimates.
OPTIMUM was a multicenter, randomized, double-blind active-controlled superiority phase 3 study (NCT02425644) conducted by a group of investigators including Robert J. Fox, MD, neurologist, Mellen Center for MS Treatment and Research, and vice-chair for research, Neurological Institute, Cleveland Clinic. The dataset included 1133 patients randomized 1:1 to 20-mg ponesimod or 14-mg teriflunomide once-daily for 108 weeks, of which 86.9% (n = 985) completed the full study.
For ARR, the ponesimod group had a rate of 0.202 compared with 0.290 for the teriflunomide group (relative rate reduction, 30.5%; P = .0003). Similarly, the mean change from baseline in fatigue symptom and impact questionnaire-RMS (FSIQ-RMS) scores were 0.01 versus 3.57 (P = .0019).
The respective ponesimod versus teriflunomide findings for the mean number of combined unique active lesions per year (CUALs) per year on MRI were 1.405 for the ponesimod group versus 3.164 for the teriflunomide group (relative rate reduction, 56%; P <.0001). Brain volume loss at Week 108 for the ponesimod and teriflunomide groups respectively were −0.91% and −1.25% (reduced by 0.34% points; P <.0001), while NEDA-3 was achieved in 25.0% and 16.4% of patients, respectively (odds ratio [OR], 1.70; P = .0004).
The time to 12-week confirmed disability accumulation risk estimates were reduced by 17% (ponesimod: 10.1%; teriflunomide: 12.4%; P = .2939), and time to 24-week confirmed disability accumulation risk estimates were reduced by 16% (ponesimod: 8.1%; teriflunomide: 9.9%; P = .3720).
In March, Janssen submitted a new drug application for ponesimod to the FDA for the treatment of adults with relapsing MS, supported by data from the OPTIMUM study.2 At the time, Husseini Manji, MD, FRCPC, Global Therapeutic Area Head for Neuroscience at Janssen Research & Development, LLC, said in a statement that “fatigue is one of the most common and debilitating symptoms of MS and yet, it's one of the most challenging to manage and treat. We were thrilled to see improvement in fatigue-related symptoms as part of the phase 3 OPTIMUM trial as we know the profound impact it may have on a person's daily life. The improvement in fatigue, coupled with reduction in ARR, demonstrates great promise for ponesimod with patients seeking a more targeted treatment option."
Additionally, the MS therapy was also being assessed in the phase 3 POINT trial (NCT02907177), which aimed to compare the S1P modulator in a 20-mg dose in measurements of efficacy, safety, and tolerability compared to placebo in those with MS who were currently being treated with twice-daily dimethyl fumarate (Tecfidera, Biogen). Although, the study was recently terminated after it failed to reach the target enrollment.
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1. Fox R, Kappos L, Burcklen M, et al. Efficacy Outcome Measures of Oral Ponesimod Compared to Teriflunomide in Patients with Relapsing Multiple Sclerosis: Results of the Randomized, Active-Controlled, Double-Blind, Parallel-Group Phase 3 OPTIMUM Study. Neurology. 2020;94(15 Suppl): 3972.
2. Janssen Submits Ponesimod New Drug Application to the U.S. FDA for Treatment of Adults with Relapsing Multiple Sclerosis [news release]. Titusville, NJ: The Janssen Pharmaceutical Companies of Johnson & Johnson. March 18, 2020. prnewswire.com/news-releases/janssen-submits-ponesimod-new-drug-application-to-the-us-fda-for-treatment-of-adults-with-relapsing-multiple-sclerosis-301026319.html