One-year histologic outcomes reported in phase III study of mirikizumab compared to ustekinumab for Crohn's disease

VIVID-1 is the first Phase III study for any approved or investigational treatment in Crohn's disease to report histologic and combined histologic-endoscopic outcomes that were evaluated using a systematic assessment of five bowel segments (four colonic and one ileal) and strict definitions consistent with the recently published European Crohn's and Colitis (ECCO) position statement on mucosal histopathology. These results are being presented as an oral presentation at United European Gastroenterology (UEG) Week, held in Vienna, Austria from October 12-15.

Mirikizumab is an IL23p19 antagonist that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. Inflammation due to the overactivation of the IL-23 pathway plays a critical role in pathogenesis of Crohn's disease, a chronic, inflammatory bowel disease associated with progressive bowel damage, disability and decreased health-related quality of life.

Crohn's disease inflammation occurs at the cellular level—defined as histologic inflammation—and persists even after treatment with standard of care therapies in up to one-quarter of patients with Crohn's disease despite evidence of endoscopic mucosal healing.

"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, M.D., Ph.D., head of clinical pharmacology at University Hospital São João. "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."

In VIVID-1, mirikizumab achieved nominally statistically significant improvements across all histologic and histologic-endoscopic endpoints versus placebo at Weeks 12 and 52, and versus ustekinumab on the following endpoints. A greater number of patients that achieved histologic response were observed with mirikizumab at Week 52 in the overall population (58.2% versus 48.8%; p=0.0075). In patients with active histologic disease at baseline and with at least one prior biologic failure, mirikizumab also showed greater histologic response at Week 52 (56.5% versus 41.3%; p=0.0064) and endoscopic-histologic response at Week 52 (39.6% versus 27.8%; p=0.024).

The overall safety profile of mirikizumab in patients with moderately to severely active Crohn's disease was consistent with the known safety profile in patients with ulcerative colitis (UC). The frequency of serious adverse events was greater in placebo than mirikizumab. The most common adverse events were COVID-19, anemia, arthralgia, headache, upper respiratory tract infection, nasopharyngitis and injection site reactions. 

"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, M.D., 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 around the globe, including in the U.S., Europe, Japan and China. Additional global regulatory submissions are planned.

Lilly is committed to finding solutions to elevate care and improve treatment outcomes for people living with inflammatory bowel disease, which includes studying the long-term efficacy and safety of mirikizumab in pediatric patients (NCT05509777 and NCT04844606) and adults (NCT04232553).

Mirikizumab is approved for the treatment of moderately to severely active UC in adults and is marketed as Omvoh (mirikizumab has additional ongoing trials in UC, including a study in pediatric patients (NCT05784246) and a study to evaluate the long-term efficacy and safety of mirikizumab in adults (NCT03519945). Lilly is continuing to advance the science with an open-label UC trial studying two new endpoints in the assessment of bowel urgency with frequency and deferral time, both of which impact the quality of life for patients (NCT05767021).

About the VIVID-1 Clinical Trial Program

VIVID-1 was a Phase III, randomized, double-blind, treat-through study that evaluated the safety and efficacy of mirikizumab compared with placebo and an active control (ustekinumab) in adults with moderately to severely active Crohn's disease. Patients randomized to mirikizumab were administered 900 mg of mirikizumab intravenously every four weeks from Week 0-12, then 300 mg subcutaneously every four weeks from Weeks 12-52. In this study, 49% of patients taking mirikizumab or placebo had experienced a prior biologic failure.