Etrasimod

Etrasimod is a synthetic next-generation selective Sphingosine 1-phosphate (S1P) receptor modulator that targets the S1P with no detectable activity on S1P and S1P receptors. S1P receptors are membrane-derived lysophospholipid signaling molecules that are involved in the sequestration of circulating peripheral lymphocytes in lymph nodes. Therefore, S1P receptor modulators like etrasimod were investigated in treating immune-mediated diseases like ulcerative colitis where a high level of inflammatory T cells is present in the gastrointestinal tract, thus causing diffuse mucosal inflammation. In fact, it has been observed that antigen-activated T cells within peripheral lymphoid organs can transiently downregulate S1P receptor levels to facilitate immune cells trafficking into the intestinal mucosa.

Etrasimod was approved on October 13, 2023, by the FDA under the brand name VELSIPITY for the treatment of adults with moderately to severely active ulcerative colitis. This approval was based on favorable results obtained from Pfizer’s Elevate UC Phase III registrational program, consisting of the Elevate UC 52 and Elevate UC 12 clinical trials, that investigates the efficacy of a 2-mg daily dose regimen of etrasimod, with a 32% and 26% remission rate observed in UC 52 and UC 12 trials respectively.