Lilly's Mirikizumab Achieves Primary and All Key Secondary Endpoints in Phase 3 LUCENT-2 Maintenance Study for Ulcerative Colitis

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

Notably, 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 the p19 subunit of IL-23. It 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 comprises three studies: LUCENT-1, LUCENT-2, and LUCENT-3 (NCT03519945), with the final study conducted in patients who have already participated in mirikizumab's UC clinical trials. 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 colon lining and may 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. Globally, millions of people suffer from UC.

Inflammatory Bowel Disease: Therapeutic Targets (Image sourced from PMID30478416)

In the 12-week induction study LUCENT-1, patients who achieved a clinical response with mirikizumab treatment were re-randomized in the maintenance study LUCENT-2 to receive either mirikizumab maintenance therapy or placebo. Data showed that a statistically significantly higher proportion of patients in the mirikizumab maintenance group reached the primary endpoint of clinical remission after one year compared to the placebo group (p<0.001). Clinical remission is achieved when colon inflammation is controlled or resolved, leading to normalization or near-normalization of symptoms such as stool frequency and bleeding.

In addition, the 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 bowel 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 Lilly plans to submit a Biologics License Application (BLA) for mirikizumab to the U.S. FDA in the first half of 2022, followed by marketing applications to other global regulatory authorities.

Note: The original text has been abridged.

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

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