Experimental Medications: NEW S1P Receptor Modulators
- Oral medication being studied at 20 mg per day
- Being studied in RRMS
Ponesimod is another selective S1P1 receptor modulator that completed a Phase II trial; results were reported in 2012.22 In this study, 462 people with RRMS 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 generated an increase in adverse events, which included swelling of the extremities and difficulty breathing. With an 83 percent decrease in gadolinium-enhancing lesions and a favorable adverse event profile, the 20 mg dose of ponesimod may have the best benefit-to-risk profile in this trial. An extension trial over two years (presented in 2013) demonstrated continued efficacy and no new safety issues.
In spring 2015, Actelion decided to advance this agent to a Phase III trial in RRMS: OPTIMUM,23 a multicenter, randomized, double-blind study to compare the efficacy and safety of ponesimod to Aubagio in subjects with relapsing forms of multiple sclerosis. The study aims to determine whether ponesimod is more effective than Aubagio in reducing relapses. The study is expected to enroll approximately 1,100 subjects, randomized in two groups in a 1:1 ratio to receive ponesimod 20 mg per day or Aubagio 14 mg per day, and is expected to last approximately three years.24
A second, large trial is currently underway that employs a combination approach; 600 participants will be randomized either to Tecfidera alone or Tecfidera plus ponesimod in order to understand if there is an added benefit in terms of disease control when the two agents are combined. The POINT study (POnesImod aNd Tecfidera) is of interest as it is the largest study in MS to look at a combination of oral agents.