Phase 2 Study Indicates Mirikizumab Induces Mucosal Healing in Patients With Ulcerative Colitis

New phase 2 data demonstrated that gene expression changes induced by mirikizumab (Eli Lilly and Company) in patients with ulcerative colitis (UC) were maintained for up to 1 year, according to a press release from Lilly. These changes, which were induced over a 12-week treatment period and were unique among individuals who responded to mirikizumab compared to placebo, were associated with mucosal healing. According to the investigators, this indicates that mirikizumab affects a distinct molecular healing pathway when compared to the spontaneous healing that occurred among the cohort administered the placebo.

As indicated in the results of a prior phase 2 study evaluating the use of mirikizumab in patients with UC, the drug successfully down-regulated multiple gene transcripts correlated with inflamed mucosa and up-regulated gene transcripts associated with healthy mucosa, as well as markers of functional healing after 12 weeks.

In the current study, a set of differentially expressed gene transcripts were identified in participants who responded to mirikizumab compared with the patients responding to placebo. Seventy-one percent of the modulated genes were present only in patients who responded to mirikizumab, 5.6% were present only in patients who responded to placebo, and 23.6% were present in both cohorts. Those gene transcripts regulated by mirikizumab were associated with UC disease activity indices, which the investigators said demonstrated consistent molecular changes across the categories of symptomatic, clinical, endoscopic, and histological indices of UC disease activity.

“In the first clinical study of an anti-IL-23p19 therapy in ulcerative colitis to evaluate gene expression on this large scale, mirikizumab demonstrated an ability to down-regulate the gene transcripts associated with inflammation and up-regulate transcripts associated with mucosal healing in ulcerative colitis, with changes maintained for up to one year,” said Walter Reinisch, director of the Clinical IBD Study Group in the Department of Gastroenterology and Hepatology at the Medical University of Vienna, in a press release. “These results support the continued development of mirikizumab as a potential treatment option for ulcerative colitis, given the importance of mucosal healing and functional healing as key treatment goals for this difficult-to-treat disease.”

Mirikizumab is currently being studied in phase 3 trials in patients with UC and Crohn disease, 2 forms of inflammatory bowel disease that can disrupt daily life and potentially result in serious and debilitating symptoms.

REFERENCE

Mirikizumab Up-Regulates Genes Associated with Mucosal Healing in Ulcerative Colitis for Up to One Year in Phase 2 Study [news release]. Eli Lilly and Company; July 9, 2021. Accessed July 9, 2021. http://lilly.mediaroom.com/2021-07-09-Mirikizumab-Up-Regulates-Genes-Associated-with-Mucosal-Healing-in-Ulcerative-Colitis-for-Up-to-One-Year-in-Phase-2-Study