Phase 2 Trial of Anti-TL1A Monoclonal Antibody Tulisokibart for Ulcerative Colitis
Bruce E Sands1, Brian G Feagan1, Laurent Peyrin-Biroulet1
1From the Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York (B.E.S.); the Departments of Medicine, Epidemiology, and Biostatistics, Western University, London, ON (B.G.F.), and the Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, University of Calgary, Calgary, AB (C.M.) - both in Canada; the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan (S.D.); the University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago (D.T.R.); Prometheus Biosciences, a subsidiary of Merck, Rahway, NJ (O.L., A.L., D.D.N., J. Lu, M.Y.); the Department of Gastroenterology, Melita Medical (J. Leszczyszyn), and the Department of Gastroenterology and Hepatology, Wroclaw Medical University (R.K.) - both in Wroclaw, Poland; F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles (D.P.B.M., S.T.); and GI Alliance, Southlake, TX (T.E.R.).
Background:
Tulisokibart is a tumor necrosis factor-like cytokine 1A (TL1A) monoclonal antibody in development for the treatment of moderately to severely active ulcerative colitis. A genetic-based diagnostic test was designed to identify patients with an increased likelihood of response.
Methods:
We randomly assigned patients with glucocorticoid dependence or failure of conventional or advanced therapies for ulcerative colitis to receive intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10) or placebo. Cohort 1 included patients regardless of status with respect to the test for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response. The primary analysis was performed in cohort 1; the primary end point was clinical remission at week 12. Patients with a positive test for likelihood of response from cohorts 1 and 2 were combined in prespecified analyses.
Results:
In cohort 1, a total of 135 patients underwent randomization. A significantly higher percentage of patients who received tulisokibart had clinical remission than those who received placebo (26% vs. 1%; difference, 25 percentage points; 95% confidence interval [CI], 14 to 37; P<0.001). In cohort 2, a total of 43 patients underwent randomization. A total of 75 patients with a positive test for likelihood of response underwent randomization across both cohorts. Among patients with a positive test for likelihood of response (cohorts 1 and 2 combined), clinical remission occurred in a higher percentage of patients who received tulisokibart than in those who received placebo (32% vs. 11%; difference, 21 percentage points; 95% CI, 2 to 38; P = 0.02). Among all the enrolled patients, the incidence of adverse events was similar in the tulisokibart and placebo groups; most adverse events were mild to moderate in severity.
Conclusions:
In this short-term trial, tulisokibart was more effective than placebo in inducing clinical remission in patients with moderately to severely active ulcerative colitis. (Funded by Prometheus Biosciences, a subsidiary of Merck; ARTEMIS-UC ClinicalTrials.gov number, NCT04996797.).
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