Efficacy and Safety of Etrasimod in a Phase 2 Randomized Trial of Patients with Ulcerative Colitis.
Gastroenterology. 2019 Nov 08;:
Authors: Sandborn WJ, Peyrin-Biroulet L, Zhang J, Chiorean M, Vermeire S, Lee SD, Kühbacher T, Yacyshyn B, Cabell CH, Naik SU, Klassen P, Panés J
BACKGROUND AND AIMS: Etrasimod (APD334) is an oral, selective sphingosine 1-phosphate receptor modulator in development for immune-mediated inflammatory disorders. We assessed the efficacy and safety of etrasimod in patients with moderately to severely active ulcerative colitis (UC).
METHODS: In a phase 2, proof of concept, double-blind, parallel-group study, adult outpatients with modified Mayo Clinic scores (MCSs; stool frequency, rectal bleeding, and endoscopy findings) of 4-9, endoscopic subscores of 2 or more, and rectal bleeding subscores of 1 or more were randomly assigned to groups given once-daily etrasimod 1 mg (n=52), etrasimod 2 mg (n=50), or placebo (n=54) for 12 weeks. The study was performed from October 15, 2015 through February 14, 2018 at 87 centers in 17 countries. The primary endpoint was an increase in the mean improvement in modified MCS from baseline to week 12. Secondary endpoints included the proportion of patients with endoscopic improvement (subscores of 1 or less) from baseline to week 12. Exploratory endpoints, including clinical remission, are reported in the manuscript, although the study was only statistically powered to draw conclusions on the primary endpoint.
RESULTS: At week 12, the etrasimod 2 mg group met the primary and all secondary endpoints. Etrasimod 2 mg led to a significantly greater increase in mean improvement in modified MCS from baseline than placebo (difference from placebo, 0.99 points; 90% CI, 0.30-1.68; P=.009), and etrasimod 1 mg led to an increase in mean improvement from baseline in modified MCS of 0.43 points more than placebo (90% CI, reduction of 0.24 to increase of 1.11; nominal P=.15). Endoscopic improvement occurred in 41.8% of patients receiving etrasimod 2 mg vs 17.8% receiving placebo (P=.003). Most adverse events were mild to moderate. Three patients had a transient, asymptomatic, low-grade atrioventricular block that resolved spontaneously and did not recur with further dosing; 2 of the 3 patients had evidence of atrioventricular block prior to etrasimod exposure.
CONCLUSIONS: In patients with moderately to severely active UC, etrasimod 2 mg was more effective than placebo in producing clinical and endoscopic improvements. Further clinical development is warranted. Clinicaltrials.gov no: NCT02447302.
PMID: 31711921 [PubMed – as supplied by publisher]