An international, multi-center Phase 2 trial has revealed promising results for tulisokibart, an investigational monoclonal antibody, in treating patients with moderate to severe ulcerative colitis (UC). The study, published in The New England Journal of Medicine, demonstrated that tulisokibart significantly outperformed placebo in achieving clinical remission, particularly in patients identified as likely responders through a genetic-based diagnostic test. This research offers a potential new avenue for patients who have not found relief with conventional therapies.
Targeting TL1A in Ulcerative Colitis
Ulcerative colitis, a form of inflammatory bowel disease (IBD), affects approximately 900,000 individuals in the United States, causing inflammation and ulcers in the colon. Current treatments often fall short of providing adequate relief, highlighting the need for innovative therapeutic strategies. Tulisokibart targets tumor necrosis factor-like cytokine 1A (TL1A), a protein implicated in the inflammatory process of UC. By binding to TL1A, tulisokibart prevents it from interacting with its receptor, DR3, thereby dampening inflammatory T-cell activity.
Bruce E. Sands, MD, MS, Principal Investigator and the Dr. Burrill B. Crohn Professor of Medicine, Icahn School of Medicine at Mount Sinai, explained, “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. 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.”
Study Design and Key Findings
The ARTEMIS-UC trial involved 178 adults across 14 countries with moderate to severe active UC. Participants were either dependent on glucocorticoids or had experienced failure with conventional or advanced therapies. The trial consisted of two cohorts: the first enrolled patients regardless of their companion diagnostic test status (n=135), while the second included only patients who tested positive for the companion diagnostic (Dx-positive) (n=43).
Patients were randomized to receive either intravenous tulisokibart (1,000 mg on day 1 and 500 mg at weeks 2, 6, and 10) or placebo. The primary endpoint was clinical remission at week 12, defined as a modified Mayo endoscopic subscore of 0 or 1, a rectal-bleeding subscore of 0, and a stool-frequency subscore of 0 or 1 that was not higher than the baseline value.
Key findings from the study include:
- In cohort 1, 26.5% of patients receiving tulisokibart achieved clinical remission at week 12, compared to only 1.5% in the placebo group (P<0.001).
- Among Dx-positive patients from both cohorts, 31.6% receiving tulisokibart achieved clinical remission, compared to 10.8% in the placebo group (P=0.02).
- Tulisokibart also demonstrated superiority over placebo in secondary endpoints, such as endoscopic improvement and clinical response.
- The incidence of adverse events was similar between the tulisokibart and placebo groups, with most events being mild to moderate in severity.
Precision Medicine Approach
A notable aspect of the ARTEMIS-UC trial was the incorporation of a genetic-based diagnostic test to predict response to tulisokibart. This precision medicine approach aims to identify patients most likely to benefit from the therapy. Dermot McGovern, MD, PhD, director of Translational Research in the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai, emphasized the potential of this approach, stating, “Previously, we have only been able to prescribe a medication to a patient that we think will work well, but going forward we could imagine telling the patient, 'Actually, the genetic test suggests that you would be more likely to respond to this therapy.'”
Future Directions
These encouraging Phase 2 results have paved the way for Phase 3 clinical trials to further evaluate the efficacy and safety of tulisokibart in a larger patient population. These trials will also focus on understanding the mechanisms behind TL1A inhibition and identifying biomarkers that predict patient response to optimize personalized treatment strategies.
Stephan Targan, MD, study senior author and IBD research pioneer, the Feintech Family Chair in Inflammatory Bowel Disease and executive director of the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai, noted, "Findings from this study are poised to have a remarkable impact on treatment for ulcerative colitis and IBD overall. The investigational therapy was generated based on the concept of precision medicine; it shows promise as being both anti-inflammatory and anti-fibrotic; it represents a potential turning point in drug development and discovery; and it could change how this complex disease is treated in the future."
If validated and approved, tulisokibart could offer a valuable new treatment option for patients with moderate to severe ulcerative colitis, particularly those who have failed other therapies.
