Mirikizumab, the first and only IL23p19 antagonist to show efficacy and safety in ulcerative colitis and Crohn’s disease.

Eli Lilly announces results from two multi-year phase III studies showing that patients treated with mirikizumab maintain stable long-term remission in two types of inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease. Data from two studies, LUCENT-3 in moderate to severe active UC and VIVID-2 in moderate to severe active Crohn’s disease, will be presented at the annual meeting of the American College of Gastroenterology (ACG) in late October in Philadelphia.

Mirikizumab is an interleukin-23p19 (IL23p19) antagonist that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor.. Inflammation caused by overactivation of the IL-23 pathway plays a critical role in the pathogenesis of UC and Crohn’s disease. Inflammation in UC and Crohn’s disease can cause unpleasant symptoms, such as urge to defecate, which can reduce health-related quality of life and cause potentially irreversible complications in patients if left untreated. Mirikizumab is licensed in the United States for the treatment of moderately to severely active UC in adults and is being studied by the US Food and Drug Administration (FDA) for the treatment of moderately to severely active Crohn’s disease.

“Mirikizumab is the first and only IL23p19 antagonist to provide data on long-term sustained efficacy over several years in both ulcerative colitis and Crohn’s disease.“Said Mark Genovese, senior vice president of immunology development at Lilly. “This achievement reflects our commitment to helping people with compromised immune systems maintain long-term remission and reduce the burden of disease.”

Long-term data in adults with UC

V LUTSENT-3, mIrikizumab helped patients with moderate to severe active UC achieve long-term results, including histological endoscopic mucosal remission, defined as mucosal healing.. Mirikizumab also provided sustained improvements in symptomatic, clinical, endoscopic and histological parameters for up to three years, regardless of prior failure of TNF inhibitors, tofacitinib or other biologics.

Among those who achieved clinical remission with mirikizumab at one year in the LUCENT-2 trial, The following results were achieved based on an analysis of cases observed after two additional years of treatment. (up to three years in total):

• 81% of patients maintained long-term clinical remission.
• 82% achieved long-term endoscopic remission.
• 72% achieved healing of the mucous membrane
• 79% achieved clinical remission without corticosteroids.

Patients demonstrated clinically significant, sustained improvement in the reduction of bowel urgency symptoms.. These results were also assessed using a modified non-responder calculation and are presented below in the “About the Mirikizumab Ulcerative Colitis Program” section. Among patients treated with mirikizumab in the LUCENT-3 trial, 7.4% of patients reported serious adverse events (AEs) and 5.3% discontinued treatment due to AEs. The long-term safety profile in patients with moderate to severe active UC was consistent with the known safety profile of mirikizumab. These findings were recently published in the journal Inflammatory Bowel Disease.

Long-term data in adults with Crohn’s disease

New data from phase 2 patients enrolled in the long-term extension study VIVID-2 demonstrated that patients with moderate to severe active Crohn’s disease treated with mirikizumab maintained high rates of clinical and endoscopic remission over time. Based on the analysis of cases observed after three additional years of treatment (up to a total of five years), the following results were obtained:

• 96% of patients had a clinical response as measured by the Crohn’s Disease Activity Index (CDAI).
• 87% were in clinical remission as measured by the CDAI.
• 76% had endoscopic response
• Endoscopic remission was observed in 54% of patients.

These results were also assessed using a modified non-responder calculation and are presented below in the “About the Mirikizumab Crohn’s Disease Program” section. “TO Despite ongoing advances, people with ulcerative colitis and Crohn’s disease continue to seek treatments to relieve difficult-to-treat symptoms. such as bowel urgency, and which provide durable results over time,” said Bruce Sands, professor of medicine and chief of the Dr. Henry D. Janowitz Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai. “These longitudinal data show that mirikizumab is a targeted therapy that can, over time, promote gut healing and improve key symptoms that matter most to patients,”

Among these patients enrolled in the long-term extension study VIVID-2, 8.5% reported serious adverse events (AEs) and 1.9% discontinued treatment due to AEs. The long-term safety profile in patients with moderate to severe Crohn’s disease was consistent. already known about mirikizumab. Omvox (mirikizumab-MRKZ) was approved by the FDA in October 2023 as the first IL23p19 antagonist for the treatment of moderately to severely active UC in adults and is approved in 44 countries worldwide. Lilly has filed applications to market mirikizumab for the treatment of Crohn’s disease worldwide, including the United States, Canada, Europe, Japan and China. There are plans to submit more authorization applications worldwide.

Except, Lilly is conducting a combination study in UC with mirikizumab and eltrekibart, a humanized monoclonal antibody that binds to seven ligands signaling through the chemokine receptors CXCR1 and CXCR2. is involved in the movement of neutrophils to sites of inflammation (NCT06598943). Studies are also ongoing in UC (NCT05611671) and Crohn’s disease (NCT06226883) using MORF-057, a selective oral small molecule inhibitor of alpha-4/beta-7 integrins that may improve outcomes and expand treatment options for patients with IBD.

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