Eli Lilly's IL-23 Inhibitor Mirikizumab Shows Positive Phase 2 Results in Crohn’s Disease, Paving Way for Phase 3 Trial

Recently, at the Digestive Disease Week (DDW) medical conference in the United States, Eli Lilly and Company announced positive results from a Phase 2 clinical trial of its developed IL-23 inhibitor, mirikizumab, for treating patients with moderate-to-severe Crohn’s disease. The trial results demonstrated that, compared to placebo, mirikizumab significantly reduced clinically and endoscopically measured disease activity after 12 weeks of treatment. Eli Lilly plans to initiate Phase 3 clinical trials later this year.

Crohn’s disease is a chronic inflammatory bowel disease (IBD) characterized by immune-mediated inflammation of the gastrointestinal tract. The most commonly affected areas are the terminal ileum and the proximal colon; however, it can involve any part of the gastrointestinal tract. IBD, which includes Crohn’s disease and ulcerative colitis, affects the lives of 10 million people worldwide.

Mirikizumab is a fully humanized monoclonal antibody targeting the p19 subunit of IL-23, developed by Eli Lilly and Company. The IL-23/IL-17 signaling pathway plays a pivotal role in the pathogenesis of various chronic inflammatory diseases, and research into this pathway has led to the development of several blockbuster drugs, including Janssen’s Stelara, AbbVie’s Skyrizi, and Novartis’s Cosentyx. Mirikizumab is currently being evaluated in multiple clinical trials for the treatment of various immune-mediated diseases, including psoriasis, ulcerative colitis, and Crohn’s disease.

▲ Innovative Therapies Targeting the IL-23/IL-17 Signaling Pathway (Image source: Reference [2])

In the SERENITY trial, a randomized, double-blind, placebo-controlled Phase 2 clinical study, patients with moderately to severely active Crohn’s disease received treatment with varying doses of mirikizumab or placebo. The primary endpoint was the endoscopic response rate at Week 12, defined as a ≥50% reduction from baseline in the Simple Endoscopic Score for Crohn’s Disease (SES-CD). Secondary endpoints included clinical remission assessed by Patient-Reported Outcomes (PROs) and safety.

Trial results demonstrated that mirikizumab met the primary and key secondary endpoints of the study:

· In terms of endoscopic remission rates, the remission rates for patient groups receiving 200 mg, 600 mg, and 1000 mg doses of mirikizumab were 25.8%, 37.5%, and 43.8%, respectively, while the rate in the placebo group was 10.9%.

· In terms of PRO clinical remission rates, the remission rates for patients receiving 200 mg, 600 mg, and 1000 mg doses of mirikizumab were 12.9%, 28.1%, and 21.9%, respectively, compared to 6.3% in the placebo group.

“Following the announcement of positive Phase 2 clinical results for mirikizumab in the treatment of moderate-to-severe ulcerative colitis last year, we are pleased to return to DDW this year and present additional positive findings on mirikizumab for the treatment of chronic inflammatory gastrointestinal diseases,” said Dr. Lotus Mallbris, Vice President of Immunology Development at Eli Lilly and Company. “We hope that mirikizumab will help raise the standard of care for patients with Crohn’s disease, and we look forward to initiating Phase 3 clinical trials to further evaluate the efficacy and safety of mirikizumab in the treatment of Crohn’s disease.”

References:

[1] Lilly's Mirikizumab Met Primary Endpoint and Key Secondary Endpoints in Phase 2 Study, Including Reductions of Gastrointestinal Lesions. Retrieved May 21, 2019, from https://www.prnewswire.com/news-releases/lillys-mirikizumab-met-primary-endpoint-and-key-secondary-endpoints-in-phase-2-study-including-reductions-of-gastrointestinal-lesions-300854236.html

[2] Biachi and Rogge (2019). The IL-23/IL-17 pathway in human chronic inflammatory diseases—

new insight from genetics and targeted therapies. Genes & Immunity, https://doi.org/10.1038/s41435-019-0067-y

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