Phase 2b data published in The Lancet Gastroenterology & Hepatology show duvakitug significantly improved clinical remission in ulcerative colitis with favorable safety.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
Duvakitug, an investigational monoclonal antibody targeting tumor necrosis factor-like cytokine 1A (TL1A), achieved significantly higher clinical remission rates than placebo in adults with moderately to severely active ulcerative colitis, according to Phase 2b results published in The Lancet Gastroenterology & Hepatology. The findings support TL1A inhibition as a promising therapeutic strategy for patients who have not responded adequately to conventional or advanced therapies.
Duvakitug Demonstrates Significant Clinical Benefit
The multicenter, randomized, placebo-controlled Phase 2b trial (NCT05499130) enrolled adults aged 18 to 75 years with moderately to severely active ulcerative colitis, including patients with inadequate response, loss of response, or intolerance to previous conventional or advanced treatments. The study evaluated two maintenance doses of subcutaneous duvakitug following a 2,250 mg loading dose.
The primary endpoint was clinical remission at week 14, assessed using the modified Mayo score and analyzed with a Bayesian statistical approach.
Among 137 randomized patients included in the modified intention-to-treat analysis, clinical remission was achieved in:
- 36% (17 of 47) of patients receiving duvakitug 450 mg
- 48% (22 of 46) of patients receiving duvakitug 900 mg
- 20% (9 of 44) of patients receiving placebo
Both dose groups exceeded the prespecified threshold for efficacy. The posterior probability of superiority over placebo reached 0.95 for the 450 mg regimen and greater than 0.99 for the 900 mg regimen, with the higher dose demonstrating the strongest treatment effect.
Targeting TL1A in Ulcerative Colitis
Ulcerative colitis is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon and rectum. Despite the availability of biologics and small-molecule therapies, many patients experience inadequate response or loss of treatment benefit over time.
Duvakitug is a fully human monoclonal antibody that selectively blocks TL1A, a cytokine involved in intestinal inflammation and tissue remodeling. Increasing evidence suggests that TL1A contributes to both inflammatory activity and fibrosis in inflammatory bowel disease, making it an attractive therapeutic target beyond traditional anti-TNF approaches.
Approximately one-third of participants in the study had previously received an approved advanced therapy, reflecting a population with substantial unmet treatment needs.
Safety Profile Remained Comparable to Placebo
Duvakitug demonstrated a favorable safety profile throughout the 14-week treatment period.
Adverse events occurred in:
- 49% of patients receiving 450 mg
- 43% of patients receiving 900 mg
- 52% of patients receiving placebo
The most frequently reported adverse events included upper respiratory tract infections and anemia. Serious adverse events were uncommon, with one case of non-infective oophoritis reported in the 900 mg treatment group and one intracranial hemorrhage reported in the placebo group.
Investigators reported no new safety concerns associated with TL1A inhibition during the study.
Publication Strengthens Evidence for TL1A Blockade
The study was funded by Teva and Sanofi and enrolled patients between September 2022 and November 2024.
Publication of these findings in The Lancet Gastroenterology & Hepatology adds peer-reviewed evidence supporting TL1A inhibition as a potential new treatment approach for ulcerative colitis. The robust efficacy observed with the 900 mg regimen, combined with a placebo-like safety profile, provides a strong rationale for advancing duvakitug into late-stage clinical development.
If confirmed in larger Phase 3 studies, duvakitug could expand the growing pipeline of targeted therapies available for patients with ulcerative colitis, particularly those who have exhausted existing biologic and advanced treatment options.
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About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office