Janssen has announced positive, top-line results from its Phase 3 OPTIMUM study, testing the effectiveness and safety of ponesimod tablets, compared to Sanofi‘s Aubagio (teriflunomide), in adults with relapsing forms of multiple sclerosis (MS).
The data will support submissions to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) seeking ponesimod’s approval as a treatment for people with relapsing MS. Those applications are planned for later this year.
The study’s data also will be presented soon at this year’s congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), taking place Sept. 11-13 in Stockholm, Sweden.
Ponesimod (formerly ACT-128800) is a selective sphingosine-1-phosphate receptor 1 (S1P1) modulator, a class of compounds believed to stop immune cells (lymphocytes) from leaving lymph nodes by blocking S1P signaling.
Ponesimod reduces the number of inflammatory cells circulating in the blood, which reduces the chances of these cells infiltrating the brain and spinal cord, causing injury to myelin (the insulating sheath around nerve cells that is damaged in people with MS).
The OPTIMUM study was a global Phase 3 trial (NCT02425644) comparing the effectiveness, tolerability, and safety of ponesimod versus Aubagio, which is another oral therapy for relapsing MS.
The study was conducted at multiple centers worldwide, and recruited a total of 1,133 adult patients with active relapsing MS, specifically relapsing-remitting MS (RRMS) and active secondary progressive MS (SPMS).
Participants were randomly assigned either to once-daily ponesimod tablets (20 mg per day), or once-daily Aubagio tablets (14 mg per day), over 108 weeks (approximately two years).
The primary outcome measure, or endpoint, was change from study start to study end in annualized relapse rate (ARR), measured as the number of flares per year per subject. Relapses are new, worsening or recurrent neurological symptoms that last for more than one day in the absence of fever or infections. They may be resolved in days or weeks, or lead to persistent deficits and greater disability.
Another key goal of the study was change in fatigue-related symptoms, an important unaddressed symptom in MS, Janssen says. Additional efficacy measures included the cumulative number of combined unique active lesions seen on MRI scans, and the time to first 12-week and 24-week confirmed disability accumulation.
Ponesimod’s safety was consistent with previous studies, and the known safety profile for other S1P receptor modulators.
The investigational therapy is being developed by Actelion Pharmaceuticals, part of Janssen, the pharmaceutical company of Johnson & Johnson. Actelion holds an agreement with Idorsia Pharmaceuticals, which provides for sharing revenues from potential sales of ponesimod.