Mirikizumab Demonstrates Superiority over Placebo in Phase 3 Maintenance Study in Ulcerative Colitis, Supporting Regulatory Submissions in 2022

December 16, 2021 /BioValleyBIOON/ --Eli Lilly(Eli Lilly) recently announced that the randomized, double-blind, placebo-controlled Phase 3 maintenance study LUCENT-2 (NCT03524092) evaluating the novel anti-inflammatory drug mirikizumab for the treatment of moderate to severe active ulcerative colitis (UC) has reached the one-year time point (52 weeks).Achieved the primary endpoint and all key secondary endpointsThe LUCENT-2 study enrolled patients who had completed another 12-week, Phase 3 induction study, LUCENT-1 (NCT03518086). The LUCENT-1 study was conducted in patients with moderate to severe UC who had failed treatment with conventional and/or biologic therapies, and its positive top-line results were announced in March 2021.

It is worth mentioning that,Mirikizumab is the first and only anti-IL23p19 antibody to demonstrate maintenance of clinical remission in Phase 3 studies for the treatment of UC.Mirikizumab is a humanized IgG4 monoclonal antibody that targets and binds to the p19 subunit of IL-23. This drug is currently under development for various immune-mediated diseases, including plaque psoriasis (PsO), ulcerative colitis (UC), and Crohn's disease (CD). UC and CD are two types of inflammatory bowel disease that can cause severe and debilitating symptoms, interfering with daily life.

The Phase 3 clinical program LUCENT for mirikizumab in the treatment of UC includes three studies: LUCENT-1, LUCENT-2, and LUCENT-3 (NCT03519945). The last study involved participants who had already been treated with mirikizumab for UC.Clinical Trialin patients. The program was initiated in 2018, and complete results from the induction and maintenance studies are expected to be released in early 2022.

UC is a chronic inflammatory disease of the large intestine (also known as the colon), which affects the lining of the colon and can lead to the formation of small sores or ulcers. This inflammation can cause abdominal pain, frequent and urgent bowel movements, bloody stools, and incontinence. UC can result in severe and debilitating disruptions in daily life. Millions of people worldwide are affected by UC.

Bruce E. Sands, Chief of Gastroenterology at the Icahn School of Medicine at Mount Sinai, stated: "In this maintenance study, mirikizumab treatment demonstrated clinically meaningful and statistically significant improvements in clinical, endoscopic, and histologic aspects, includingReducing Bowel Urgency – A Novel Endpoint in the LUCENT ProgramIntestinal urgency is one of the most bothersome and disruptive symptoms experienced by patients with ulcerative colitis. The LUCENT program leverages innovative, systematic approaches.A Patient-Centered Approach to Assessing Patients' Symptoms。”

Patients who achieved a clinical response to mirikizumab treatment in the 12-week induction study LUCENT-1 were re-randomized in the maintenance study LUCENT-2 to receive either mirikizumab maintenance therapy or placebo. The data showed,Compared with the placebo group, a statistically significantly higher proportion of patients in the mirikizumab maintenance therapy group reached the primary endpoint of clinical remission after one year (p＜0.001).When the inflammation of the colon is controlled or alleviated, leading to normalization or near-normalization of symptoms such as bowel frequency and bleeding, clinical remission can be achieved.

In addition,LUCENT-2 study also met all key secondary endpoints (p<0.001).Compared with the placebo group, a significantly higher proportion of patients in the mirikizumab maintenance therapy group achieved endoscopic remission, corticosteroid-free remission, complete or near-complete elimination of bowel urgency, improvement in endoscopic and histologic intestinal inflammation, sustained remission, and greater reduction in bowel urgency symptoms from baseline after one year.

In the placebo-controlled maintenance cohort, patients treated with mirikizumab had a numerically lower frequency of serious adverse events compared to placebo. The overall safety profile was consistent with previous studies of mirikizumab in UC and other studies of the anti-IL-23p19 antibody class. The most common treatment-emergent adverse events in patients receiving mirikizumab were nasopharyngitis, arthralgia, and ulcerative colitis worsening. Other adverse events reported in patients receiving mirikizumab included hypersensitivity, injection site reactions, depression, elevated liver enzymes, herpes zoster, and oral candidiasis.

Based on these data,Eli LillyPlanned for the first half of 2022 in the United StatesFDASubmit the Biologics License Application (BLA) for mirikizumab, and subsequently file marketing applications with other regulatory agencies worldwide.

Eli LillyGlobalImmunology"Current treatments do not fully meet the needs of patients with ulcerative colitis, who still experience unresolved symptoms that impact their health and quality of life. These positive long-term results provide evidence that mirikizumab has the potential to be an effective treatment option and the first anti-IL23p19 antibody for treating patients with ulcerative colitis, including those with urgency." (Bioon.com)

Source of the original text:Mirikizumab Demonstrates Superiority over Placebo in Phase 3 Maintenance Study in Ulcerative Colitis, Supporting Regulatory Submissions in 2022