S1P receptor modulators face uncertain future in Crohn’s disease amid trial setbacks

Pfizer’s upcoming presentation at United European Gastroenterology Week (UEGW) 2024 will reveal the initial findings from its CULTIVATE study of its sphingosine-1-phosphate (S1P) receptor modulator Velsipity (etrasimod) in Crohn’s disease (CD), showing modest efficacy in endoscopic response and remission rates. With its in-class competitor ozanimod also underperforming in trials, the outlook for S1P receptor modulators in Crohn’s disease remains uncertain, highlighting challenges in addressing this complex condition, says GlobalData.

Earlier this year, Bristol Myers Squibb (BMS) reported that Zeposia (ozanimod), which is an in-class competitor of etrasimod, did not meet its primary endpoint of clinical remission in its Phase III YELLOWSTONE study.

Gaja Gasiorek, Senior Immunology Analyst at GlobalData, comments, “Zeposia has been approved for the treatment of ulcerative colitis, another sub-indication of inflammatory bowel disease, since 2021 (US and EU). However, many clinicians have struggled to position it in the ulcerative colitis treatment algorithm due to its lower efficacy, high cost, and burdensome pre-initiation requirements. In contrast, Velsipity, with lower pricing and robust patient support, has recently gained approval in the US and EU, securing a foothold in the S1P ulcerative colitis market.”

GlobalData’s Ulcerative Colitis Market Forecast expects Zeposia to have sales of $374.2 million worldwide in 2031, compared to sales of $423.2 million for Velsipity, despite its later market entry.

While both inflammatory bowel disease conditions are characterised by chronic inflammation of the digestive tract, CD trial endpoints are much harder to meet due to the need for endoscopic improvement.

Gasiorek concludes, “Given the ozanimod’s failure to meet YELLOWSTONE trial’s primary endpoints in CD, as well as the low endoscopic efficacy of etrasimod seen in CULTIVATE, it is unlikely for either of the S1P receptor modulators to be approved in this indication.

“Despite their presence in ulcerative colitis, the efficacy of S1PR modulators in CD is questionable, either simply due to weak endoscopic benefit or because of ineffective dosing regimens, and further limited by the safety issues associated with this drug class. Additionally, the limited utility of this drug class in the wider inflammatory bowel disease treatment algorithm could affect future prescribing habits and impact sales.”