Arena Pharmaceuticals announced positive topline Phase 2 results from the OASIS trial for etrasimod, an investigational, once-daily, orally administered, selective sphingosine 1-phosphate (S1P) receptor modulator in development for the treatment of ulcerative colitis (UC). Patients receiving the 2 mg dose of etrasimod achieved statistically significant improvements versus placebo in the primary, all secondary, and clinical remission endpoints.
Relative to placebo, there was a statistically significant (p = 0.009) 0.99 point improvement in a 3-component (stool frequency, rectal bleeding and findings on endoscopy) Mayo Clinic Score (ranging from 0 to 9) with etrasimod 2 mg at week 12. In the 1 mg group, there was a 0.43 point improvement in 3-component Mayo Clinic Score at week 12 relative to placebo, which was not statistically significant (p = 0.146). Significantly more patients in the etrasimod 2 mg group achieved endoscopic improvement compared with placebo (41.8% vs. 17.8%, p = 0.003).
The proportion of patients achieving clinical remission, defined by the 3-component Mayo Clinic Score, was 33.0% in the etrasimod 2 mg group compared to 8.1% for the placebo group (p < 0.001). Remission as defined by the 4-component Total Mayo Clinic Score was 24.5% and 6.0% for etrasimod 2 mg and placebo, respectively (p = 0.004).
Etrasimod was well tolerated and there were fewer patients with serious adverse events (SAEs) compared to placebo (0% in 2 mg, 5.8% in 1 mg and 11.1% in placebo). Impact on heart rate and atrioventricular (AV) conduction was low throughout the study with no discontinuations from study related to bradycardia or AV block. There were no increases in liver function tests compared to placebo and no reports of macular edema or pulmonary function test abnormalities. The company plans to present full study results at future medical congresses.
"The results of this Phase 2 trial are impressive and demonstrate statistically significant efficacy of orally administered etrasimod, including clinically meaningful improvement in remission, as well as endoscopic improvement in what has been historically referred to as mucosal healing," said William Sandborn, M.D., Professor of Medicine and Chief, Division of Gastroenterology and Director, University of California San Diego Inflammatory Bowel Disease Center. "Despite recent advances in treatment options, there remains a significant unmet need for new oral therapies for ulcerative colitis. I look forward to etrasimod advancing into a Phase 3 program."