Newswise — New York, NY (September 25, 2024) – A phase 2 trial of a monoclonal antibody known as tulisokibart for moderate-to-severe ulcerative colitis (UC) showed promising results for those who have not responded to conventional inflammatory bowel disease (IBD) treatment.
The Mount Sinai-led trial was the first large study to demonstrate tulisokibart’s significant benefits in reducing inflammation and inducing remission in these patients. It will be published tomorrow, Thursday, September 26, in The New England Journal of Medicine.
UC is a type of IBD that primarily affects the colon and rectum. The inflammation can lead to symptoms such as abdominal pain, diarrhea, and rectal bleeding. Millions of people worldwide are affected by UC, and both men and women are impacted.
“Managing ulcerative colitis often requires a personalized approach and ongoing adjustments based on the patient’s response to therapy, especially for patients with more severe cases,” said Bruce E. Sands, MD, MS, Principal Investigator and the Dr. Burrill B. Crohn Professor of Medicine, Icahn School of Medicine at Mount Sinai. “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.” Dr. Sands is also Chief of the Dr. Henry D. Janowitz Division of Gastroenterology at the Mount Sinai Health System.
The study 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. 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 (1000mg on day 1 and 500mg 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,” said 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.”
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