Mirikizumab Demonstrates Superiority to Ustekinumab in Treating Crohn Disease

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Results from the Phase III Vivid-1 trial have shown that Lilly’s mirikizumab offered a higher number of histologic responses at week 52 than ustekinumab in patients with Crohn's disease. According to the company, these results are significant, as they align with the European Crohn's and Colitis (ECCO) position statement on mucosal histopathology. Full results were presented earlier this week at the United European Gastroenterology conference in Vienna, Austria.¹

"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 Fernando Magro, MD, PhD, head, clinical pharmacology, University Hospital São João, in a press release. "These histologic data build on the growing body of evidence for mirikizumab, which may provide a greater depth of mucosal healing for those living with this chronic, progressive disease."

The randomized, double-blind, treat-through VIVID-1 study evaluated the safety and efficacy of mirikizumab compared with placebo and ustekinumab in adults with moderately to severely active Crohn disease. In the study, patients randomly assigned to receive mirikizumab were administered 900 mg intravenously every four weeks from weeks zero to 12, then 300 mg subcutaneously every four weeks from weeks 12-52. Forty-nine percent of patients who were taking mirikizumab or placebo had experienced a prior biologic failure. The primary endpoint of the study was nominally statistically significant improvements across all histologic and histologic-endoscopic endpoints versus placebo at weeks 12 and 52 versus placebo.

Results found that at week 52, 58.2% of patients in the mirikizumab group achieved histologic response compared to 48.8% of patients in the placebo group. Additionally, mirikizumab showed greater histologic response in patients with active histologic disease at baseline and with at least one prior biologic failure and endoscopic-histologic response, accounting for 39.6% of the group, with 27.8% of the placebo group experiencing the same.

The safety profile of mirikizumab was found to be consistent with the known safety profile in patients with ulcerative colitis. Serious adverse events (AEs) were found to be more frequent in patients in the placebo arm of the study. Common AEs included COVID-19, anemia, arthralgia, headache, upper respiratory tract infection, nasopharyngitis, and injection site reactions. Additionally, Lilly warns that mirikizumab can cause hypersensitivity reactions, a number of infections, tuberculosis, and hepatotoxicity.¹

According to Medline Plus, Crohn disease is most common in western Europe and North America, with a prevalence of 100 to 300 per 100,000 people. Currently, over half a million people in the United States are living with Crohn disease. It is most common in people of northern European ancestry and those of eastern and central European Jewish descent than among people of other ethnic backgrounds. While it is currently unknown why, the prevalence of Crohn disease has been increasing in the United States and some other parts of the world in recent years.²

"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. This includes more ambitious targets of mucosal healing, which we applied to compare mirikizumab's histo-endoscopic effect to ustekinumab," said Mark Genovese, MD, SVP, Lilly immunology development, in the press release. "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."

References

1. Lilly reports one-year histologic outcomes in Phase 3 study of mirikizumab compared to ustekinumab for Crohn's disease. Lilly. October 14, 2024. Accessed October 16, 2024. https://investor.lilly.com/news-releases/news-release-details/lilly-reports-one-year-histologic-outcomes-phase-3-study

2. Crohn's disease. Medline Plus. Accessed October 16, 2024. https://medlineplus.gov/genetics/condition/crohns-disease/#frequency