Positive results for TL1A inhibitor duvakitug in CD

The investigational TNF ligand 1A (TL1A) inhibitor duvakitug was associated with clinically meaningful endoscopic response rates in patients with moderately to severely active Crohn’s disease (CD). The agent was well-tolerated in the current phase 2b study, supporting further evaluation of this drug in CD.

“TL1A is an important mediator of inflammation and fibrosis in inflammatory bowel disease,” explained Prof. Vipul Jairath (Western University, Canada) [1]. “Duvakitug is a human IgG1 monoclonal antibody, designed to inhibit TL1A via DR3 while preserving the binding of TL1A to [decoy receptor] DcR3.”

In the phase 2b RELIEVE UCCD trial (NCT05499130), participants with CD or ulcerative colitis (UC) received duvakitug 900 mg, duvakitug 450 mg, or a placebo, subcutaneously injected every 2 weeks. The primary endpoint was endoscopic response at week 14. Prof. Jairath presented findings from the CD cohort (n=138). “There was no cap on prior received therapies, an important aspect of the study design,” emphasised Prof. Jairath. He showed that 43% of the participants with CD had not received prior advanced therapy, whereas 57% had been treated with at least 1 advanced treatment.

At week 14, the primary endpoint was reached by 48% of the participants in the high-dose arm (P<0.001), by 26% of the participants in the low-dose arm (P=0.058), and by 13% in the placebo arm. In the advanced therapy-naïve arm, the endoscopic response rates were 47% in both duvakitug groups and 23% in the placebo group. The results were quite different in the advanced therapy-experienced group, with endoscopic response rates of 48% in the 900 mg arm, 11% in the 450 mg arm, and 7% in the placebo arm.

Serious adverse events were reported in 11% of the participants in the placebo arm, in 13% of those in the 450 mg arm, and only in 2% of the participants in the 900 mg arm. “Duvakitug was well-tolerated, and we did not see emergent safety signals,” expressed Prof. Jairath.

“These results support further development of duvakitug as a potential treatment option for patients with moderately to severely active CD,” concluded Prof. Jairath.

1. Jairath V, et al. Duvakitug (TEV-48574), an anti-TL1A monoclonal antibody, demonstrates efficacy and favourable safety as an induction treatment in adults with moderately to severely active Crohn’s disease: results from a phase 2b, randomized, double-blind, placebo-controlled dose-ranging, basket trial (RELIEVE UCCD). OP40, 20th Congress of ECCO, 19–22 February 2025, Berlin, Germany.

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Posted on 8 April 20258 April 2025