Experimental Medications: New S1P Receptor Modulators
- Oral medication being studied at 20 mg per day
- Being studied in RMS
Ponesimod is another selective S1P1 receptor modulator that completed a Phase II trial; results were reported in 2012. In this study, 462 people with RMS were randomized to placebo or 10 mg, 20 mg, or 40 mg of ponesimod. Reductions in annualized relapse rate and reductions in new lesions were seen for all treatment groups versus placebo. However, the 40-mg dose was associated with an increase in adverse events. Two randomized, doubleblind, phase III trials involving the 20-mg dose are now under way.
The POINT study is examining ponesimod as adjunctive therapy to Tecfidera® (dimethyl fumarate). Investigators are following approximately 600 individuals with RRMS who had been taking Tecfidera for at least six months at screening. The participants, all of whom are being randomized at a 1:1 ratio to add-on ponesimod 20 mg/d or placebo for 60 weeks, showed clinical or MRI evidence of disease activity within 12 to 15 months of screening. Major endpoints will include annual relapse rate, clinical and MRI disease activity, and measures of the safety and tolerability of ponesimod. Study completion is scheduled for March 2020.69, 70
Meanwhile, the ongoing OPTIMUM (Oral Ponesimod Versus Teriflunomide in Relapsing MUltiple Sclerosis) trial is comparing ponesimod and teriflunomide (Aubagio®) in patients with RMS. A total of 1,133 participants have been randomized to ponesimod 20 mg/d or teriflunomide 14 mg/d over 108 weeks. Investigators are measuring annualized relapse rate, changes in fatigue symptoms, cumulative number of T1 enhancing or T2 lesions on MRI, and prevalence of patients who report confirmed disability at 12 and 24 weeks. The trial is scheduled for completion in May 2019.71