Teva Pharmaceutical Industries and Sanofi announced positive results from their Phase 2b RELIEVE UCCD study of duvakitug, a monoclonal antibody targeting TL1A, for the treatment of moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD). The study met its primary endpoints in both UC and CD patients, suggesting a potential new treatment option for inflammatory bowel disease (IBD).
The RELIEVE UCCD study, a 14-week, randomized, double-blind, dose-ranging trial, evaluated the efficacy, safety, pharmacokinetics, and tolerability of duvakitug in adult patients with moderate-to-severe UC or CD. Patients were administered either a low dose (450 mg), a high dose (900 mg) of duvakitug, or a placebo every two weeks subcutaneously.
Efficacy in Ulcerative Colitis
In the UC cohort, 36% of patients receiving the 450 mg dose and 48% receiving the 900 mg dose of duvakitug achieved clinical remission at week 14, compared to 20% in the placebo group. The placebo-adjusted rates were 16% and 27%, respectively (p=0.050 and 0.003). Higher clinical remission rates were observed in both advanced therapy (AT)-experienced and AT-naïve subgroups.
- AT-experienced: 29% (450 mg) and 36% (900 mg), with placebo-adjusted rates of 22% and 29%.
- AT-naïve: 39% (450 mg) and 53% (900 mg), with placebo-adjusted rates of 12% and 26%.
Additional endpoints observed in the UC cohort included:
- Clinical response (mMS): 81% (450 mg) and 70% (900 mg) compared to 52% with placebo.
- Endoscopic improvement (MES): 45% (450 mg) and 50% (900 mg) compared to 23% with placebo.
- Histological-endoscopic mucosal improvement (HEMI): 30% (450 mg) and 33% (900 mg) compared to 16% with placebo.
Efficacy in Crohn's Disease
In the CD cohort, 26% of patients receiving the 450 mg dose and 48% receiving the 900 mg dose of duvakitug achieved endoscopic response at week 14, compared to 13% in the placebo group. The placebo-adjusted rates were 13% and 35%, respectively (p=0.058 and <0.001).
Similar to the UC cohort, higher endoscopic response rates were observed in both AT-experienced and AT-naïve subgroups.
- AT-experienced: 11% (450 mg) and 48% (900 mg), with placebo-adjusted rates of 7% and 44%.
- AT-naïve: 47% (450 mg) and 47% (900 mg), with placebo-adjusted rates of 25% and 25%.
Additional endpoints observed in the CD cohort included:
- Endoscopic remission (SES-CD): 17% (450 mg) and 26% (900 mg) compared to 9% with placebo.
- Clinical remission (CDAI): 50% (450 mg) and 54% (900 mg) compared to 41% with placebo.
- Clinical response (CDAI): 61% (450 mg) and 62% (900 mg) compared to 41% with placebo.
- Clinical response (PRO2): 50% (450 mg) and 53% (900 mg) compared to 29% with placebo.
Safety and Tolerability
Duvakitug was generally well-tolerated in both the UC and CD cohorts, with no emergent safety signals observed. The rates of treatment-emergent adverse events were comparable between the duvakitug and placebo groups, and no dose-dependent or adverse event pattern was observed for treatment-related AEs, SAEs, AEs leading to discontinuation, or AESIs.
Expert Commentary
Walter Reinisch, MD, PhD, lead investigator of the RELIEVE UCCD study, commented on the potential of duvakitug to transform treatment for patients with IBD in a safe manner, highlighting the significant treatment response compared to placebo in both advanced therapy-naïve and experienced patients with ulcerative colitis.
Vipul Jairath, MBChB, DPhil, FRCP, FRCPC, lead investigator for the CD cohort, emphasized the potential of duvakitug as an effective new option for Crohn’s disease patients in desperate need of relief, citing the endoscopic response rates observed in the study.
Next Steps
The findings from the RELIEVE UCCD study will form the basis for a Phase 3 program, anticipated to start in H2 2025. Teva will host an investor call to discuss the new data presented at the 20th Annual Congress of the European Crohn's and Colitis Organization (ECCO).
Collaboration
Teva and Sanofi are collaborating to co-develop and co-commercialize duvakitug for the treatment of UC and CD. Sanofi will lead the Phase 3 clinical development program, while Teva will lead commercialization in Europe, Israel, and specified other countries. Sanofi will lead commercialization in North America, Japan, other parts of Asia, and the rest of the world.
