Eli Lilly's IL-23 Antibody Mirikizumab Meets Phase 3 Primary Endpoint, Significantly Improving Symptoms in Patients with Ulcerative Colitis

Today, Eli Lilly and Company announced that its anti-IL-23p19 antibody mirikizumab met the primary endpoint and all key secondary endpoints in the Phase 3 LUCENT-1 clinical trial evaluating patients with moderate-to-severe ulcerative colitis (UC). The press release noted that LUCENT-1 is the first Phase 3 clinical trial to demonstrate that an IL-23p19 antibody can reduce urgency of defecation in patients with moderate-to-severe UC.

Ulcerative colitis (UC) is a disease caused by chronic inflammation of the large intestine. It causes abdominal pain, bloody diarrhea, severe urgency to defecate, weight loss, and fatigue. The severity of symptoms and the unpredictability of disease flares place a heavy burden on patients and often lead to disability. Millions of people worldwide are affected by UC.

Mirikizumab is a humanized IgG4 monoclonal antibody that binds to the p19 subunit of IL-23, thereby blocking IL-23-mediated inflammatory responses. Mirikizumab is currently being evaluated in multiple clinical trials for the treatment of immune-mediated diseases, including psoriasis, ulcerative colitis, and Crohn’s disease. The IL-23/IL-17 axis can be regarded as a “star signaling pathway” in the treatment of various chronic inflammatory diseases. Targeting this pathway has led to the development of several innovative therapies, including Novartis’ IL-17A antibody Cosentyx (secukinumab), Janssen’s IL-12/IL-23 antibody Stelara (ustekinumab), and AbbVie’s IL-23 antibody Skyrizi (risankizumab), among others.

Eli Lilly’s mirikizumab development program includes the 12-week randomized, double-blind induction therapy study LUCENT-1, the maintenance therapy study LUCENT-2, and the open-label extension study LUCENT-3. In the LUCENT-1 clinical trial, mirikizumab met the primary endpoint of clinical remission at 12 weeks compared with placebo (p<0.0001). Clinical remission indicates that inflammation in the colon is controlled or resolved, resulting in normalization or near-normalization of bowel movement frequency and bleeding symptoms.

Furthermore, mirikizumab met all key secondary endpoints, including reduction in stool urgency, clinical response, endoscopic remission, and improvement in endoscopic-histologic inflammation. Moreover, mirikizumab demonstrated efficacy as early as 4 weeks after initiation of treatment and reduced symptoms even in patients who had not responded to other biologics or JAK inhibitors.

“Patients with ulcerative colitis (UC) often face challenges in effectively managing the recurrent flares of their disease,” said Dr. Lotus Mallbris, Vice President of Immunology Development at Eli Lilly. “Based on these positive results, we look forward to continuing the 52-week maintenance therapy study, with the hope of providing a new treatment option for patients with UC.”

Note: This article aims to introduce medical and health research and does not constitute a recommendation for treatment plans. For guidance on treatment options, please consult a licensed healthcare provider at a reputable hospital.

References:

[1] Lilly's Mirikizumab Helps Patients Achieve Clinical Remission and Improves Symptoms in Adults with Ulcerative Colitis in 12-Week Phase 3 Induction Study. Retrieved March 16, 2021, from https://investor.lilly.com/news-releases/news-release-details/lillys-mirikizumab-helps-patients-achieve-clinical-remission-and

[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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