A first-in-class monoclonal antibody therapy proved effective in a phase 2 trial in inducing clinical remission in ulcerative colitis (UC) patients who had not responded to other treatments. The results of the Mount Sinai-led trial offer new hope to patients who have not been helped by existing advanced therapies.
The study, published in The New England Journal of Medicine, tested the effectiveness and safety of tulisokibart, a monoclonal antibody designed specifically to bind to TL1A, a protein involved in the inflammatory process of UC. This study explored whether a novel treatment pathway involving attaching to TL1A could potentially provide significant relief and better disease management for UC.
“Tulisokibart offers a new potential treatment option and addresses a critical gap in treatments for ulcerative colitis; this medication is showing promising results in regulating a patient’s immune response and promoting optimal healing,” says Bruce E. Sands, MD, MS, Principal Investigator of the trial, Dr. Burrill B. Crohn Professor of Medicine at the Icahn School of Medicine at Mount Sinai, and Chief of the Dr. Henry D. Janowitz Division of Gastroenterology at the Mount Sinai Health System.
The study of tulisokibart was the first blinded randomized controlled trial of any TL1A monoclonal antibody for any indication. No drugs in this class have yet received Food and Drug Administration approval to treat any disease.
Bruce E. Sands, MD, MS, right, led the clinical trial of a first-in-class medication, tulisokibart, for refractory ulcerative colitis.
The study also investigated the ability of a companion diagnostic test to predict response to tulisokibart. This innovative approach is a major step forward in addressing unmet treatment needs in conventional IBD therapies and improving patient outcomes and quality of life.
Eligible patients for this study had corticosteroid dependence or failure of conventional and/or advanced therapies for ulcerative colitis. These patients were randomized to receive placebo or intravenous tulisokibart (1000 mg on day 1 and 500 mg at weeks 2, 6, and 10). Cohort 1 enrolled patients regardless of their companion diagnostic test status. Cohort 2 enrolled only patients who tested positive for the companion diagnostic (Dx-positive). The primary analysis was performed on cohort 1; the primary endpoint was clinical remission at week 12. Dx-positive patients from cohorts 1 and 2 were combined in additional prespecified analyses.
In cohort 1, a total of 135 patients were randomized. A greater proportion of patients receiving tulisokibart compared with placebo achieved clinical remission (26.5% vs. 1.5%, difference 25.0%; 95% confidence interval [CI], 13.9%‒36.6%; P<0.001). In cohort 2, 43 patients were randomized. A total of 75 Dx-positive patients were randomized across both cohorts. A greater proportion of Dx-positive patients (cohorts 1 and 2 combined) receiving tulisokibart achieved clinical remission compared with placebo (31.6% vs. 10.8%, difference 20.8%; 95% CI, 2.1%‒37.9%; P=0.02). Incidence of adverse events was similar between treatment groups; most adverse events were mild to moderate in severity.
The next steps for this research include conducting larger, phase 3 clinical trials to confirm the efficacy and safety of tulisokibart in a broader patient population. Continued research will also focus on understanding the mechanisms behind TL1A inhibition and identifying biomarkers that predict patient response to optimize personalized treatment strategies. If further validated and approved for clinical use, tulisokibart could provide an additional treatment option for patients with moderate-to-severe ulcerative colitis even if other treatments have failed.
“This research paves the way for future advancements in the treatment of inflammatory bowel diseases,” says Dr. Sands. “These results highlight the potential for identifying biomarkers that can predict which patients will respond best to TL1A inhibition, paving the way for more personalized and targeted treatment strategies in the future.”