OPTIMUM Phase 3 Trial: Ponesimod’s Cardiac Safety Data


An overview of ponesimod’s cardiac safety data demonstrated by the phase 3 OPTIMUM study and its potential impact on first-dose observation recommendations.

Robert Naismith, MD: Ponesimod is another S1P that is presenting data. It’s currently in development. We have a number of S1Ps available. Just in the last year, year and a half we’ve had ozanimod and siponimod. Ponesimod is another selective S1P modulator. They did a large study on the drug vs teriflunomide and showed very good efficacy that was very much consistent, I feel, with the other S1P modulators, which also had head-to-head studies.

In this study, they evaluated patients receiving ponesimod. The way cardiac events are mediated, in terms of getting around the first-dose observation, are 2-fold. First, there’s a dose titration. We’ve seen this with siponimod and ozanimod. Second is the selectivity of the S1P1 receptor perhaps having relatively less effect on the bradycardia.

In this study, they had 565 patients on ponesimod. Again, the comparator was teriflunomide. There were no major cardiovascular events looking at strokes, MIs [myocardial infarctions], or anything along those lines in this population. They did find very low rates of bradycardia in the ponesimod arm, and nobody that had any cardiac issues needed to be discontinued from the study. Very few patients had bradycardia or low-grade heart block. I think 3 patients had heart rates under 40. They looked at if you had cardiac risk factors not, and those with no cardiac risk factors had very low rates of any bradycardia. I can’t speak precisely about how this matches up in the analysis to the other ones. We know that in terms of the other medications, the regulatory agencies were optimistic, in that the first-dose observation did not need to be done on everybody—just high-risk patients. This type of data might inform that decision when the FDA and the EMA [European Medicines Agency] and other regulators look at what might be recommended for ponesimod. We’ll have to wait and see what the decision is.

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