Ponesimod to treat multiple sclerosis

Ponesimod (ACT-128800) is a directly bioavailable, rapidly reversible sphingosine-1-phosphate (S1P) receptor modulator, highly selective for the subtype 1 (S1P₁ receptor). It acts by blocking the egress of lymphocytes from the lymphoid organs, thus limiting the entry of autoreactive cells into the central nervous system. Unlike fingolimod, ponesimod does not require monitoring of the first dose, thanks to a 14-day uptitration regimen, which markedly reduces the incidence of cardiodynamic effects related to the initiation of therapy. Results from the OPTIMUM phase III trial demonstrated the superiority of ponesimod over teriflunomide on disease activity markers, without unexpected safety concerns. Furthermore, the drug is eliminated within 1 week of discontinuation, allowing for the reversibility of its effects. Ponesimod was recently approved in both the U.S. and E.U. for the treatment of relapsing forms of multiple sclerosis. This review summarizes the pharmacological characteristics of ponesimod and the main studies that led to its approval.