Positive results were announced from a phase 3 study evaluating mirikizumab, an investigational anti-IL-23p19 monoclonal antibody, as maintenance therapy in patients with moderately to severely active ulcerative colitis (UC).
The multicenter, randomized, double-blind, placebo-controlled maintenance study LUCENT-2 (ClinicalTrials.gov Identifier: NCT03524092) evaluated the efficacy and safety of mirikizumab in UC patients who achieved clinical response in the 12-week LUCENT-1 induction study (ClinicalTrials.gov Identifier: NCT03518086). Patients were randomly assigned to mirikizumab maintenance dosing or placebo for 40 weeks. The primary endpoint was clinical remission based on modified Mayo Score at week 40.
Results showed that a statistically higher proportion of patients treated with mirikizumab achieved clinical remission at 1 year compared with those who received placebo (P <.001). Mirikizumab also met all key secondary endpoints with a significantly higher proportions of patients achieving endoscopic remission, corticosteroid-free remission, resolution or near-resolution of bowel urgency, improvement in endoscopic histologic intestinal inflammation and maintenance of remission, and greater reduction from baseline in bowel urgency symptoms at 1 year, compared with placebo (all P <.001).
The overall safety profile of mirikizumab was consistent with that seen in previous studies for UC. The most common adverse events reported were nasopharyngitis, arthralgia and exacerbation of UC.
“In this maintenance study, treatment with mirikizumab demonstrated clinically meaningful and statistically significant improvements in clinical, endoscopic and histologic measures, including reduction of bowel urgency – a novel endpoint in the LUCENT program,” said Bruce E. Sands, MD, MS, Dr. Burrill B. Crohn Professor of Medicine, Chief of the Dr Henry D. Janowitz Division of Gastroenterology at the Icahn School of Medicine at Mount Sinai. “Bowel urgency is one of the most bothersome and disruptive symptoms people living with ulcerative colitis experience, and the LUCENT program leveraged an innovative and systematic patient-centric approach to assess patients’ symptoms.”
Mirikizumab is also being evaluated in the LUCENT-3 trial (ClinicalTrials.gov Identifier: NCT03519945), an open-label extension study for eligible patients who have participated in the mirikizumab UC clinical development program.
The Company intends to submit a Biologics License Application to the Food and Drug Administration (FDA) for the UC indication in the first half of 2022. Phase 3 trials investigating mirikizumab as a treatment for Crohn disease are ongoing.
- Mirikizumab demonstrates superiority over placebo in phase 3 maintenance study in ulcerative colitis, supporting regulatory submissions in 2022. News release. Eli Lilly and Company. Accessed December 15, 2021. https://www.prnewswire.com/news-releases/mirikizumab-demonstrates-superiority-over-placebo-in-phase-3-maintenance-study-in-ulcerative-colitis-supporting-regulatory-submissions-in-2022-301444707.html.