Lilly Reports Landmark One-Year Histologic Outcomes For Mirikizumab

Eli Lilly and Company has revealed new data showing that a higher number of patients with moderately to severely active Crohn's disease who received mirikizumab achieved a histologic response at Week 52 compared to those treated with ustekinumab, irrespective of their prior exposure to biologic therapies. The VIVID-1 study marks a significant milestone as the first Phase 3 trial for any approved or experimental treatment in Crohn's disease to report histologic and combined histologic-endoscopic results. These outcomes were assessed systematically across five bowel segments—four colonic and one ileal—using strict definitions aligned with the recent European Crohn's and Colitis (ECCO) position statement on mucosal histopathology. The findings are set to be presented orally at the United European Gastroenterology (UEG) Week taking place in Vienna, Austria, from October 12-15.

Mirikizumab functions as an IL-23p19 antagonist, specifically targeting and binding to the p19 subunit of IL-23, thereby blocking its interaction with the IL-23 receptor. The overactivation of the IL-23 pathway significantly contributes to the inflammation seen in Crohn's disease, which is a chronic inflammatory bowel condition that leads to progressive intestinal damage, disability, and a decline in health-related quality of life. Inflammation associated with Crohn's disease is characterised by histologic changes at the cellular level, and this type of inflammation can continue even after patients receive standard care treatments. In fact, up to 25% of patients may still experience histologic inflammation despite showing signs of endoscopic mucosal healing.

Fernando Magro, M.D., Ph.D., head of clinical pharmacology at University Hospital São João, stated, "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. 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 the VIVID-1 study, mirikizumab demonstrated statistically significant improvements in all histologic and combined histologic-endoscopic endpoints compared to placebo at both Weeks 12 and 52, as well as when compared to ustekinumab for specific endpoints. By Week 52, a higher percentage of patients treated with mirikizumab achieved a histologic response, with 58.2% responding compared to 48.8% for placebo (p=0.0075). 

Among patients with active histologic disease at the start of the trial who had previously failed at least one biologic treatment, mirikizumab also exhibited better results at Week 52, showing a histologic response of 56.5% versus 41.3% (p=0.0064) and an endoscopic-histologic response of 39.6% compared to 27.8% for ustekinumab (p=0.024).

The safety profile of mirikizumab in individuals with moderately to severely active Crohn's disease aligned with its established safety profile observed in ulcerative colitis (UC) patients. Notably, serious adverse events were reported more frequently in the placebo group than in those receiving mirikizumab. The most prevalent adverse events included COVID-19, anaemia, arthralgia, headaches, upper respiratory tract infections, nasopharyngitis, and reactions at the injection site.

Mark Genovese, M.D., senior vice president of Lilly Immunology development, said in a statement, "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. 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 filed marketing authorization applications for mirikizumab for the treatment of Crohn's disease in several regions worldwide, including the U.S., Europe, Japan, and China, with plans for additional regulatory submissions globally. The company is dedicated to enhancing care and improving treatment outcomes for individuals with inflammatory bowel disease. This includes ongoing studies investigating the long-term efficacy and safety of mirikizumab in both paediatric (NCT05509777 and NCT04844606) and adult (NCT04232553) populations.

Currently, mirikizumab is approved for treating moderately to severely active ulcerative colitis (UC) in adults under the brand name Omvoh™. Additionally, there are several ongoing clinical trials for mirikizumab in UC, including one focused on paediatric patients (NCT05784246) and another examining its long-term efficacy and safety in adults (NCT03519945). Lilly is also progressing in research with an open-label UC trial that aims to assess two new endpoints related to bowel urgency—frequency and deferral time—both of which significantly affect patients' quality of life (NCT05767021).