Though no details have been reported, Janssen Pharmaceuticals announced that its S1P modulator ponesimod has met its primary and key secondary end points in the OPTIMUM study, in which it was compared to teriflunomide in patients with relapsing MS.
Jean-Paul Clozel, MD, chief executive officer, Actelion
Jean-Paul Clozel, MD
Ponesimod has met its primary end point along with most of its secondary end points in a recent phase 3 study comparing it to teriflunomide (Aubagio, Sanofi) in adults with multiple sclerosis (MS), according to its manufacturer, the Janssen Pharmaceuticals Companies of Johnson & Johnson.1
The data will be the foundation of ponesimod’s submission to the FDA and other regulatory agencies as a treatment for relapsing MS, expected to come later this year. The therapy is being developed by Actelion Pharmaceuticals Ltd.
The selective sphingosine-1-phosphate receptor 1 (S1P1) modulator was assessed for its effect on annualized relapse rate, the primary end point, in the OPTIMUM study (NCT02425644), from baseline through the end of the trial. The secondary end points included the change in fatigue-related symptoms through week 108, deemed a key end point, as well as the cumulative number of combined unique active MRI lesions, and time to first 12-week and 24-week confirmed disability accumulation.
"I have always believed that combination therapy is the future for the treatment of relapsing multiple sclerosis,” Jean-Paul Clozel, MD, chief executive officer, Actelion, said in a statement in January.2 “The properties of ponesimod, supported by our preclinical knowledge and clinical results, all point towards ponesimod being ideally suited for use in combination.”
The trial included 1133 patients who were randomized to either 20-mg ponesimod or 14-mg teriflunomide for 108 weeks in a double-blind, active-controlled, parallel, multicenter fashion. The data is expected to be presented at the 35th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), taking place September 11-13, in Stockholm, Sweden.
Ponesimod was developed to inhibit lymphocytes from leaving lymph nodes, thus rapidly reducing circulating blood lymphocyte counts and preventing the infiltration of lymphocytes into the targeted tissues. Previously, in a double-blind, placebo-controlled, dose-finding phase 2b study, Tomas Olsson, MD, PhD, and colleagues found that ponesimod was well-tolerated in doses of 10, 20, or 40 mg, and significantly reduced the number of new T1 Gd+ lesions at weeks 12—24 of the 24-week trial.3
In January, Guy Braunstein, MD, head, Global Clinical Development, Actelion Ltd., said in a statement that the "clinical development program for ponesimod in multiple sclerosis was already innovative when we decided to move into phase 3. OPTIMUM is the first study in MS to target superiority over a commercialized oral therapy. It also includes a number of patient-oriented outcome assessments."
As of yet, the safety profile of ponesimod in the OPTIMUM study was consistent with what was observed in previous studies, and the known safety profile for other S1P receptor modulators.
The MS therapy is also being assessed int the ongoing phase 3 POINT trial ((NCT02907177), which is comparing the S1P modulator in a 20-mg dose in measurements of efficacy, safety, and tolerability compared to placebo in those with MS who are currently being treated with twice-daily dimethyl fumarate (Tecfidera, Biogen).
The primary outcome in POINT is the confirmed relapses per subject-year as compared to placebo. Secondary end points include confirmed disability accumulation, time to first confirmed relapse, combined unique active lesions per post-baseline scan, longitudinal change over time in fatigue-related symptoms, and longitudinal percent change from baseline over time in brain volume.
“With POINT, the first trial in active RMS adding one oral drug to another, we will assess the clinical utility of combination therapy with ponesimod, to offer patients better control of their disease,” Braunstein said in a statement in January. The study’s target enrollment is 600 patients, and it is expected to be completed in March 2020.
1. Janssen reports positive top-line Phase 3 results for ponesimod in adults with relapsing multiple sclerosis [press release]. Titusville, NJ: Janssen; Published July 25, 2019. prnewswire.com/news-releases/janssen-reports-positive-top-line-phase-3-results-for-ponesimod-in-adults-with-relapsing-multiple-sclerosis-300891338.html. Accessed July 26, 2019.
2. Slaughter E. OPTIMUM Phase 3 Trial for Multiple Sclerosis Nearing Completion. MD Mag website. mdmag.com/medical-news/optimum-phase-3-trial-multiple-sclerosis. Published January 11, 2019. Accessed July 26, 2019.
3. Olsson T, Boster A, Fernandez O, et al. Oral ponesimod in relapsing—remitting multiple sclerosis: a randomised phase II trial. J Neurol Neurosur Ps. 2014;85:1198-1208. doi: 10.1136/jnnp-2013-307282.