S1877 Duvakitug, an Anti-TL1a mAb, Demonstrates Efficacy and Favorable Safety as an Induction Treatment in Adults With Moderately to Severely Active Ulcerative Colitis: Results From the RELIEVE UCCD Phase 2b Basket Trial

Introduction: Duvakitug is a human IgG1 monoclonal antibody selected for its preferential inhibition of TL1A-DR3 signaling over DcR3 binding. Duvakitug has demonstrated reduced inflammation and fibrosis in colitis animal models. The efficacy and safety of duvakitug in adults with moderately to severely active ulcerative colitis (UC) and Crohn’s disease was assessed in a phase 2b basket trial (NCT05499130). Methods: RELIEVE UCCD was a randomized, placebo (PBO)-controlled, double-blind induction study. The UC cohort comprised of adults with moderately to severely active disease with inadequate response, loss of response or intolerance to previous conventional and/or advanced therapies (ATs). Eligible patients were randomized to receive subcutaneously a 2250 mg loading dose of duvakitug or PBO, followed by either duvakitug 450 mg, 900 mg or PBO (1:1:1; stratified by prior AT) every 2 weeks. The primary endpoint was clinical remission (per modified Mayo score) at week 14. Safety was assessed by adverse event (AE) reporting and laboratory monitoring. Results: In total, 137 patients were randomized, treated and included in the UC cohort analysis (450 mg: n = 47; 900 mg: n = 46; PBO: n = 44). Demographics and baseline characteristics were generally similar across arms. Both duvakitug doses successfully achieved the week 14 primary endpoint of clinical remission (36% [450 mg], 48% [900 mg] vs 20% [PBO]; PBO-adjusted rates: 16% [450 mg], 27% [900 mg]). The results were statistically significant based on the prespecified Bayesian analysis, with a >0.90 posterior probability that each duvakitug dose is superior to PBO. Duvakitug treatment effect was observed in both AT-experienced and -naïve patients. AE incidence was lower for duvakitug (49% [450 mg], 43% [900 mg]) vs PBO (52%), as was incidence of AEs leading to discontinuation (0% [450 mg], 2% [900 mg] vs 5% [PBO]). Conclusion: Duvakitug demonstrated statistically significant and clinically meaningful treatment responses compared to PBO in patients with UC; it was well tolerated with no emergent safety signals observed. These induction study results support further development of duvakitug as a potential treatment option for patients with moderately to severely active UC.