Eli Lilly's mirikizumab demonstrated superior histologic response compared to ustekinumab in patients with moderately to severely active Crohn's disease, according to results from the Phase III VIVID-1 trial presented at the United European Gastroenterology conference in Vienna, Austria. The study, which evaluated the safety and efficacy of mirikizumab versus placebo and ustekinumab, showed that mirikizumab could offer a greater depth of mucosal healing for individuals living with this chronic condition.
The VIVID-1 study was a randomized, double-blind trial where patients received either mirikizumab (900 mg intravenously every four weeks for the first 12 weeks, followed by 300 mg subcutaneously every four weeks) or placebo. A significant 49% of patients in both the mirikizumab and placebo groups had experienced prior biologic failure. The primary endpoint focused on improvements across histologic and histologic-endoscopic endpoints compared to placebo at weeks 12 and 52.
Key Findings from VIVID-1
At week 52, 58.2% of patients in the mirikizumab group achieved histologic response, compared to 48.8% in the ustekinumab group (p=0.0075). Furthermore, mirikizumab showed a greater histologic response in patients with active histologic disease at baseline and at least one prior biologic failure (56.5% versus 41.3%; p=0.0064). Endoscopic-histologic response was also higher in the mirikizumab group (39.6%) compared to the ustekinumab group (27.8%; p=0.024).
"Treatment strategies for Crohn's disease must evolve beyond traditional measures of clinical remission and endoscopy, to the evaluation of depth of intestinal healing by measuring histologic and transmural resolution," said Dr. Fernando Magro, head of clinical pharmacology at University Hospital São João.
Safety Profile and Adverse Events
The safety profile of mirikizumab was consistent with its established profile in ulcerative colitis. Serious adverse events were more frequent in the placebo arm of the study. Common adverse events included COVID-19, anemia, arthralgia, headache, upper respiratory tract infection, nasopharyngitis, and injection site reactions. Lilly noted potential risks of hypersensitivity reactions, infections, tuberculosis, and hepatotoxicity associated with mirikizumab.
Implications for Crohn's Disease Treatment
With Crohn's disease affecting between 100 to 300 per 100,000 people in western Europe and North America, and over half a million people in the United States, the need for effective treatments is significant. These results align with the European Crohn's and Colitis (ECCO) position statement on mucosal histopathology, potentially setting a new standard for evaluating long-term treatment response in inflammatory bowel disease.
"As the first company to report rigorous histologic and endo-histologic outcomes in Crohn's disease that align with a recent ECCO position statement, Lilly is setting a higher bar for the evaluation of long-term treatment response in inflammatory bowel disease," said Dr. Mark Genovese, senior vice president of Lilly Immunology development. "These data also broaden our understanding of the underlying inflammation that drives Crohn's disease and may represent a critical step forward in helping health care providers and their patients make more informed choices about treatment."
Lilly has submitted marketing authorization applications for mirikizumab in Crohn's disease in the U.S., Europe, Japan, and China, with additional submissions planned globally.
