Up-and-Coming Tulisokibart Succeeds in Inducing Ulcerative Colitis Remission

A phase 2 trial conducted by Bruce E. Sands, M.D., from the Icahn School of Medicine at Mount Sinai in New York and colleagues found that tulisokibart, an investigational tumor necrosis-like cytokine 1A (TL1A) monoclonal antibody, is safe and effective in inducing remission in patients with moderately to severely active ulcerative colitis (UC). The results were published in the Sept. 26, 2024, issue of the New England Journal of Medicine.

Bruce E. Sands, M.D.

TL1A is naturally present in endothelial cells, such as the intestinal lining, but is overexpressed in immune cells during inflammation. When intestinal tissues are inflamed, both TL1A and its receptor death domain receptor 3 (DR3) are upregulated.

Tulisokibart, developed by Merck subsidiary Prometheus Biosciences, binds to TL1A, thereby preventing the cytokine from attaching to its receptor DR3. Subsequently, inflammatory helper T-cell activity is dampened.

The phase 2 study called ARTEMIS-UC included 135 adults with moderately to severely active UC who were glucocorticoid dependent or had failed treatment with conventional or advanced UC therapies. The participants were randomized to receive 1,000 milligrams (mg) of intravenous tulisokibart on day 1 and 500 mg on weeks 2, 6, and 10 or placebo at the same intervals.

The researchers developed a genetic-based diagnostic test to identify patients more likely to respond to an anti-TL1A antibody. Cohort 1 included participants regardless of their status on the genetic diagnostic test. Cohort 2 included 43 patients with a positive result for likelihood of response. The study’s primary endpoint was clinical remission at 12 weeks.

The results showed that a significantly higher percentage of patients in cohort 1 who received tulisokibart achieved clinical remission at week 12 compared with those who received placebo (26% versus 1%). Additionally, a significantly greater percentage of patients across both cohorts who had positive test results for likelihood of response and received tulisokibart had clinical remission at 12 weeks compared with participants who received placebo (32% versus 11%).

Adverse events were similar between participants receiving tulisokibart or placebo and were generally considered mild.

Sands and his colleagues concluded that tulisokibart is more effective than placebo for inducing clinical remission in patients with moderately to severely active UC. A larger phase 3 trial evaluating the safety and efficacy of tulisokibart in patients with moderately to severely active UC is ongoing. Preliminary results are expected in November 2026.

The phase 2 ARTEMIS-UC study was funded by Prometheus Biosciences.