Duvakitug Meets Primary Endpoints in Phase 2b RELIEVE UCCD Study for IBD

Teva Pharmaceuticals and Sanofi have announced positive data from the phase 2b RELIEVE UCCD study of duvakitug in patients with ulcerative colitis (UC) and Crohn disease (CD).1,2

According to a December 17, 2024, press release, the study met its primary endpoints for clinical remission and endoscopic response in patients with moderate to severe inflammatory bowel disease (IBD). Of note, the primary endpoint results in both UC and CD for the high dose arm represent the greatest achieved with any tumor necrosis factor (TNF)-like ligand 1A (TL1A) monoclonal antibody. Pending regulatory discussions, Sanofi and Teva plan to initiate phase 3 development in IBD.1

“These unprecedented results show that duvakitug could represent the next frontier in treating ulcerative colitis and Crohn’s disease. If the magnitude of effect persists in the Phase 3 program, we believe we will have a differentiated medicine for IBD patients who are in urgent need of new options,” said Houman Ashrafian, MD, PhD, executive vice president and head of research and development at Sanofi.2

Duvakitug is a human IgG1-λ2 monoclonal antibody targeting TL1A, also known as TNF superfamily member 15 (TNFSF15). TL1A signaling is thought to amplify inflammation and drive fibrosis associated with IBD through binding its receptor DR3, so TL1A with duvakitug may have the potential to mitigate the over-active immune response in these conditions. While it is currently in phase 2b clinical development for UC and CD, duvakitug’s safety and efficacy have not been reviewed by any regulatory authority.1

A 14-week phase 2b, randomized, double-blinded, dose-ranging study, RELIEVE UCCD seeks to determine the efficacy, safety, pharmacokinetics, and tolerability of duvakitug in adults with moderate to severe UC or CD. Patients who met pre-specified inclusion criteria were randomly assigned to receive 1 of 2 duvakitug doses or placebo, administered subcutaneously every 2 weeks, in a 1:1:1 ratio for each indication and stratified by previous exposure to advanced IBD therapies for 14 weeks.1

Participants who completed the 14-week induction study were eligible to participate in a long-term extension study, with those who responded during the 44-week maintenance period eligible for an open-label period within the long-term extension.1

Primary efficacy endpoints for both the 14-week induction study and the 44-week maintenance study are the number of participants who show clinical remission, as defined by the modified Mayo score, in the UC cohort or the number of participants who show endoscopic response, as defined by the SES-CD endoscopic score for CD, in the CD cohort.1

In RELIEVE UCCD, 36.2% and 47.8% of patients with UC treated with low and high doses of duvakitug, respectively, achieved clinical remission compared with 20.45% on placebo. Placebo-adjusted rates were 15.7% (low-dose) and 27.4% (high-dose) at week 14 (P = .050 and .003, respectively).1

In patients with CD, 26.1% receiving the low-dose and 47.8% receiving the high-dose of duvakitug achieved endoscopic response compared to 13.0% receiving placebo, with placebo-adjusted rates of 13.0% (low-dose) and 34.8% (high-dose), at week 14 (P = .058 and <.001, respectively). Investigators noted the treatment effect was consistent across subgroups.1

Duvakitug was generally well tolerated in both UC and CD with no safety signal identified. Overall rates of treatment-emergent adverse events were similar between duvakitug and placebo across both UC and CD (50% vs 50%) and all adverse events reported were < 5%.1

“The results from the RELIEVE UCCD study have exceeded our expectations, and I am deeply moved by the potential for duvakitug to help treat and meaningfully improve the quality of life of people living with IBD,” said Eric Hughes, MD, PhD, head of global research and development and chief medical officer at Teva.1 “These positive results reinforce Teva's ability to develop and accelerate access to innovative medicines. We are excited to collaborate on the next phase of development with our partner, Sanofi, and we would like to thank the investigators and patients who participated in this study.”

References

1. Teva. Teva and Sanofi Announce Duvakitug (Anti-TL1A) Positive Phase 2b Results Demonstrating Best-in-Class Potential in Ulcerative Colitis and Crohn’s Disease. December 17, 2024. Accessed December 17, 2024. https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2024/Teva-and-Sanofi-Announce-Duvakitug-Anti-TL1A-Positive-Phase-2b-Results-Demonstrating-Best-in-Class-Potential-in-Ulcerative-Colitis-and-Crohns-Disease/default.aspx
2. Sanofi. Press Release: Duvakitug positive phase 2b results demonstrate best-in-class potential in ulcerative colitis and Crohn’s disease. December 17, 2024. Accessed December 17, 2024. https://www.sanofi.com/en/media-room/press-releases/2024/2024-12-17-12-30-00-2998154