Lilly reveals one-year histological outcomes in Phase 3 trial of mirikizumab versus ustekinumab for Crohn's disease
Results show a higher percentage of patients treated with mirikizumab achieved histological response at Week 52 compared to ustekinumab.
Eli Lilly and Company has shared new data indicating that more patients with moderate to severe Crohn's disease treated with mirikizumab achieved a histological response at the 52-week mark compared to those treated with ustekinumab, regardless of their prior exposure to biologic therapies.
This analysis, known as VIVID-1, is the first Phase 3 trial of any approved or investigational drug for Crohn's disease to report both histological and combined histological-endoscopic outcomes. These were measured using a structured evaluation of five bowel segments (four in the colon and one in the ileum) with stringent criteria based on the latest European Crohn's and Colitis (ECCO) guidelines on mucosal histopathology.
Mirikizumab works by targeting the p19 subunit of the IL-23 protein, blocking its interaction with the IL-23 receptor. The overactivation of the IL-23 pathway plays a key role in the development of Crohn's disease, a chronic inflammatory condition that causes progressive bowel damage, disability, and a reduced quality of life.
Inflammation in Crohn's disease occurs at the cellular (histological) level and often remains even after treatment, despite endoscopic evidence of mucosal healing, in up to a quarter of patients. In the VIVID-1 study, mirikizumab showed statistically significant improvements in all histological and combined histological-endoscopic measures compared to placebo at both Weeks 12 and 52, and compared to ustekinumab on key endpoints.
At Week 52, a higher percentage of patients receiving mirikizumab achieved a histological response in the overall group (58.2% versus 48.8%; p=0.0075). In patients who had active histological disease at the beginning of the study and had previously experienced failure with at least one biologic, mirikizumab also demonstrated superior histological response at Week 52 (56.5% versus 41.3%; p=0.0064) and combined endoscopic-histological response (39.6% versus 27.8%; p=0.024).
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The safety profile of mirikizumab in patients with moderate to severe Crohn's disease was consistent with its known safety profile in patients with ulcerative colitis. The incidence of serious adverse events was higher in the placebo group than in the mirikizumab group. The most frequent adverse events included COVID-19 infection, anemia, joint pain, headache, upper respiratory tract infections, nasopharyngitis, and injection site reactions.
Mirikizumab is approved for treating moderate to severe ulcerative colitis in adults under the brand name Omvoh™. It is also being evaluated in ongoing trials for ulcerative colitis, including studies in pediatric patients and an assessment of its long-term efficacy and safety in adults. Lilly is also exploring new endpoints related to bowel urgency and frequency, both of which significantly affect patients' quality of life.
VIVID-1 is a Phase 3, randomized, double-blind study designed to assess the safety and efficacy of mirikizumab compared to placebo and ustekinumab in adults with moderate to severe Crohn's disease. Patients assigned to mirikizumab received 900 mg intravenously every four weeks from Week 0 to Week 12, followed by 300 mg administered subcutaneously every four weeks from Weeks 12 to 52. In this trial, 49% of patients receiving either mirikizumab or placebo had previously experienced failure with biologic treatments.
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