- Treatment with investigational duvakitug (Teva, Sanofi) appeared to improve remission rates among patients with ulcerative colitis and endoscopic response rates in those with Crohn's disease in a phase IIb study.
- Duvakitug is an anti-tumor necrosis factor-like cytokine 1A monoclonal antibody selected for its potential to decrease inflammation and affect fibrosis.
- Duvakitug could be an effective induction therapy for patients with inflammatory bowel disease, researchers said.
Treatment with investigational duvakitug appeared to improve remission rates among patients with ulcerative colitis and endoscopic response rates in those with Crohn's disease, results from two cohorts of the phase IIb RELIEVE UCCD trial showed.
In the ulcerative colitis cohort, 36% of patients treated with duvakitug 450 mg and 48% of patients treated with duvakitug 900 mg were in clinical remission at week 14 compared with 20% of patients treated with placebo, reported Walter Reinisch, MD, of the Medical University of Vienna, and colleagues.
Among patients in the Crohn's disease cohort, 26% and 48% of patients treated with duvakitug 450 mg and 900 mg achieved an endoscopic response at week 14 compared with 13% of patients in the placebo group, reported Vipul Jairath, MBChB, of Western University in London, Ontario, and colleagues.
For both cohorts, the posterior probability of superiority to placebo was 0.95 and 0.94 in the two 450-mg groups and greater than 0.99 in the 900-mg groups, meeting the statistical threshold for declaring efficacy.
These results suggest that "duvakitug might be an effective induction therapy," the authors wrote in Lancet Gastroenterology and Hepatology.
Treatment goals for ulcerative colitis include clinical remission and endoscopic healing, which are associated with symptom alleviation, a reduced risk of surgery and hospitalization, and prevention of colorectal cancer, Reinisch and team noted. While there are several classes of available therapies for patients with moderately to severely active ulcerative colitis, they are not always effective or effectiveness diminishes over time.
For Crohn's disease, clinical remission is an "intermediate treatment target," while the long-term goal is mucosal healing, Jairath and colleagues explained. Up to 80% of patients do not reach clinical remission, and available treatments are linked to tolerability challenges.
Tumor necrosis factor-like cytokine 1A (TL1A) is a pro-inflammatory cytokine implicated in the pathogenesis of inflammatory bowel disease (IBD). Duvakitug is an anti-TL1A monoclonal antibody selected for its preferential inhibition of TL1A-death receptor 3 signaling over decoy receptor binding and its potential to decrease inflammation and affect fibrosis.
Of note, despite an association between previous exposure to an advanced therapy in IBD and a reduced effectiveness of subsequent advanced therapies, 31% and 57% of patients in the ulcerative colitis and Crohn's disease cohorts had previous exposure to an approved advanced therapy.
Thus, these findings suggest that duvakitug is potentially suitable as a therapeutic option for IBD patients regardless of treatment history, the authors noted.
RELIEVE UCCD used a basket design and was conducted at 163 sites in 19 countries across North America, Europe, and Asia.
Adults with a diagnosis of moderately to severely active ulcerative colitis or Crohn's disease for at least 3 months were eligible for inclusion. All patients had a documented intolerance, inadequate response, or loss of response to at least one conventional or advanced therapy.
Patients were randomly assigned to receive a loading dose of subcutaneous duvakitug (2,250 mg) followed by six subcutaneous duvakitug induction doses (450 mg or 900 mg) every 2 weeks or a matching placebo loading dose followed by placebo every 2 weeks.
Among the 137 patients in the ulcerative colitis cohort, mean age was 41 years, 63% were men, and 96% were white.
For the Crohn's disease cohort, 139 patients were included. Mean age was 39.5 years, 58% were men, and 95% were white.
In the ulcerative colitis cohort, the incidence of adverse events (AEs) was 49% in the 450-mg group, 43% in the 900-mg group, and 52% with placebo. The most frequent AEs were anemia, upper respiratory tract infection, nasopharyngitis, and vomiting. One serious AE occurred in both the 900-mg group (non-infective oophoritis) and the placebo group (intracranial hemorrhage).
In the Crohn's disease cohort, AEs occurred in 67% of patients in the 450-mg group, 43% in the 900-mg group, and 48% in the placebo group. The most frequent AEs were nasopharyngitis and headache. Serious AEs occurred in 13% of patients in the 450-mg group, 2% in the 900-mg group, and 11% in the placebo group.
The phase III SUNSCAPE-1 and SUNSCAPE-2 trials are investigating the therapeutic potential of duvakitug for the treatment of ulcerative colitis, while the phase III STARSCAPE-1 and STARSCAPE-2 studies have been initiated for Crohn's disease.
Disclosures
The study was funded by Teva and Sanofi.
The study authors reported multiple relationships with industry, including with Sanofi.
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