Duvakitug Shows Promising Efficacy in First Anti-TL1A Trial for Crohn's Disease
Key Insights
Duvakitug, an investigational anti-TL1A (search) monoclonal antibody from Teva Pharmaceuticals and Sanofi, demonstrated statistically significant endoscopic response rates in moderate to severe Crohn's disease (search) patients.
The phase 2b RELIEVE UCCD trial showed 48% of patients receiving 900 mg duvakitug achieved the primary endpoint compared to 13% in the placebo group.
Treatment was well tolerated with no new safety signals detected, marking the first successful placebo-controlled trial of TL1A (search) targeting in Crohn's disease (search).
Duvakitug, an investigational monoclonal antibody targeting TL1A (search), has demonstrated statistically significant and clinically meaningful efficacy in patients with moderately to severely active Crohn's disease (search), according to results from the phase 2b RELIEVE UCCD basket trial presented at the American College of Gastroenterology's 2025 Annual Scientific Meeting.
The randomized, placebo-controlled, double-blind induction trial evaluated duvakitug (TEV-48574), developed by Teva Pharmaceuticals and Sanofi, in 138 adults with moderately to severely active Crohn's disease (search) who had prior documented inadequate response, loss of response, or intolerance to conventional and/or advanced therapies.
Primary Endpoint Achievement
The study met its primary endpoint of ≥50% reduction from baseline in the Simple Endoscopic Score for Crohn's Disease (search) (SES-CD) at week 14. Results showed 26% of patients receiving duvakitug 450 mg and 48% receiving 900 mg achieved the primary endpoint, compared with 13% of the placebo group.
"Duvakitug induction therapy demonstrated statistically significant and clinically meaningful endoscopic response rates vs. placebo in a fairly refractory group of patients with moderately to severely active Crohn's disease (search)," said Vipul Jairath, MBChB, DPhil, professor of medicine, epidemiology, and biostatistics at Western University, who presented the findings.
Endoscopic response rates based on prespecified Bayesian analysis were 13% for the 450 mg dose and 35% for the 900 mg dose after placebo adjustment. The results were consistent among patients who had previously received advanced therapies and those naive to treatment.
Novel Mechanism of Action
Duvakitug is a human IgG1-λ2 monoclonal antibody targeting TL1A (search) (tumor necrosis factor superfamily member 15 (search)), designed to modulate inflammation and fibrosis associated with inflammatory bowel disease (search) pathogenesis. "TL1A is found to be a key mediator of inflammation fibrosis. It's a proinflammatory cytokine that has been implicated in IBD," Jairath explained. "It works upstream on anti-TNF and TL1A binds to its receptor DR3 (search)... and it works as an amplification of immune signals and mediated fibrosis."
Study Design and Patient Population
Participants were randomly assigned to receive a 2,250 mg subcutaneous loading dose of duvakitug or placebo, followed by maintenance doses of duvakitug 450 mg (n = 46), 900 mg (n = 46), or placebo (n = 46) administered every 2 weeks. Patients were stratified by prior recorded advanced therapies.
Most patients in the duvakitug groups completed the trial, with 93% of patients in the 900 mg group and 80% in the 450 mg group completing the study.
Safety Profile
The safety profile was consistent with previous reports, with no emergent safety signals detected. The incidence of adverse events was similar between duvakitug 900 mg (43%) and placebo (48%), though higher in the duvakitug 450 mg group (67%). Treatment-emergent adverse events were reported in six patients in each of the treatment groups and two patients in the placebo group, with no dose-dependent effects noted.
The most common adverse events were anemia, headache, and nasopharyngitis, all of which were non-serious and self-limiting. Adverse events leading to discontinuation occurred in 9% of patients receiving duvakitug 450 mg and 2% of those on duvakitug 900 mg or placebo.
"In the phase 2 trial, no new safety signals have been detected with duvakitug beyond what we expected when treating patients with Crohn's disease (search) or ulcerative colitis (search)," Jairath noted.
Clinical Significance
This represents the first placebo-controlled trial in Crohn's disease (search) of a TL1A (search)-targeting therapy, marking a significant milestone in inflammatory bowel disease (search) treatment development. "Again, you see a proof of mechanism suggesting that this class of drugs is beneficial in both UC and CD in the phase 2 program, and these have now moved forward into pivotal trials," Jairath said.
The RELIEVE UCCD study was conducted as a basket trial evaluating duvakitug in both ulcerative colitis (search) and Crohn's disease (search) under a common protocol, with the study meeting its primary endpoints in both indications as reported in December 2024.