[Pharmacological properties and clinical efficacy of sphingosine 1-phosphate (S1P) receptor modulator, Etrasimod (Velsipity® 2 mg tablets)].

Etrasimod L-arginine (Velsipity® 2 mg tablets) is a small-molecule sphingosine 1-phosphate (S1P) receptor modulator with high selectivity for the S1P receptor subtypes S1P1, S1P4, and S1P5. Through its action on S1P1, etrasimod induces receptor internalization, thereby inhibiting lymphocyte egress from lymph nodes to sites of inflammation. This mechanism is considered to reduce chronic inflammation in the colonic mucosa associated with ulcerative colitis (UC). Nonclinical pharmacology studies have shown that etrasimod preferentially activates the β-arrestin pathway, while relatively weakly activating G protein pathway associated with heart rate reduction compared to other S1P modulators. In clinical trials, first-dose bradycardia was mild and transient, and the magnitude of heart rate reduction after dose titration to 2 mg was comparable to that observed when treatment was initiated directly at 2 mg. Therefore, etrasimod can be initiated at the maintenance dose of 2 mg. In domestic and global Phase III clinical trials, once-daily oral administration of etrasimod 2 mg significantly improved clinical remission and endoscopic outcomes compared with placebo at 12 and 52 weeks in patients with moderately to severely active UC, including those with an inadequate response to biologics or Janus kinase inhibitors. The safety profile was favorable, with adverse event rates comparable to placebo and most events being mild to moderate. Based on these results, etrasimod was approved in Japan in June 2025 for moderate to severe UC with inadequate response to existing therapies. With once-daily oral dosing without titration and a favorable safety profile, etrasimod represents a new therapeutic option for UC.