Eli Lilly and Company have announced that mirikizumab met the primary and all key secondary endpoints in LUCENT-1, a 12-week Phase 3 induction study evaluating the efficacy and safety of mirikizumab for the treatment of patients with moderate to severe ulcerative colitis (UC). LUCENT-2, a multicenter, randomised, double-blind, placebo-controlled maintenance study of mirikizumab in patients who have completed the 12-week LUCENT-1 induction study is ongoing.
UC is a chronic inflammatory disease of the large intestine, also referred to as the colon, that affects the lining of the colon and may cause small sores, or ulcers, to form.i This inflammation can cause abdominal pain, frequent and urgent trips to the bathroom, bloody stools and incontinence.1 UC can cause significant and debilitating disruptions in daily life. Millions of people live with UC globally.2
“There is a continued need for additional treatments that can provide people living with ulcerative colitis relief from their most challenging symptoms. Results of this study provide further clinical evidence of the potential for mirikizumab to become the first anti-IL-23p19 biologic for the treatment of ulcerative colitis.”William J. Sandborn, MD, Professor of Medicine, and Chief, Division of Gastroenterology, University of California San Diego
In LUCENT-1, mirikizumab met the primary endpoint of clinical remission at Week 12 compared to placebo (p<0.0001). Clinical remission is met when inflammation of the colon is controlled or resolved, leading to normalization or near-normalization of symptoms such as stool frequency and bleeding.
Mirikizumab also achieved all key secondary endpoints compared to placebo at Week 12 in patients with UC with highly statistically significant p-values, including reduced bowel urgency, clinical response, endoscopic remission, symptomatic remission and improvement in endoscopic histologic inflammation. In addition, mirikizumab demonstrated rapid improvement in patient symptoms as early as four weeks after initiating treatment. Mirikizumab also reduced symptoms among patients who had previously not responded to or stopped responding to biologic and/or Janus kinase (JAK) inhibitor therapies.
In the 12-week placebo-controlled induction study of LUCENT-1, the incidence of treatment-emergent adverse events (AEs) and serious AEs among patients treated with mirikizumab was consistent with that of the previous Phase 2 mirikizumab study in UC and studies with the anti-IL-23p19 antibody class. The most common AEs included nasopharyngitis, anemia and headache for both placebo and mirikizumab-treated patients.
“People living with UC often struggle to effectively manage recurring flare ups of the disease,” said Lotus Mallbris, M.D., Ph.D., vice president of immunology development at Lilly. “With these positive results, we look forward to the continuation of the maintenance study through 52 weeks in hopes of providing a new option to people living with UC.”
The full LUCENT study results, including data from LUCENT-2 and LUCENT-3, will be disclosed at a future congress or publication.
“Ulcerative colitis can be debilitating and unpredictable for the hundreds of thousands of people living with this chronic disease,” said Dr. Caren Heller, Chief Scientific Officer for the Crohn’s & Colitis Foundation. “We’re encouraged by these promising results for a potential new treatment that may help provide symptom relief and remission.”
Mirikizumab is a humanized IgG4 monoclonal antibody that binds to the p19 subunit of interleukin 23. Mirikizumab is being studied for the treatment of immune diseases, including psoriasis, ulcerative colitis and Crohn’s disease.
About the LUCENT Clinical Trial Program
The LUCENT Phase 3 clinical development program for mirikizumab includes LUCENT-1, LUCENT-2 and LUCENT-3. LUCENT-1 (NCT03518086) is a multicenter, randomized, double-blind, placebo-controlled, Phase 3 induction study of mirikizumab in patients with moderate to severe UC who had failed conventional and/or biologic treatments. LUCENT-2 (NCT03524092) is a multicenter, randomized, double-blind, placebo-controlled maintenance study of mirikizumab in patients who have completed the 12-week LUCENT-1 induction study. LUCENT-3 (NCT03519945) is an open label extension study for eligible patients who have participated in mirikizumab UC trials.
The program began in 2018, with full results from the induction and maintenance studies anticipated in early 2022.
- Overview of Ulcerative Colitis. Crohn’s and Colitis Foundation Website. https://www.crohnscolitisfoundation.org/what-is-ulcerative-colitis/overview. Accessed February 2021.
- Adelphi Data 2017.
- What is Ulcerative Colitis? Crohn’s and Colitis Foundation Website. http://www.crohnscolitisfoundation.org/what-are-crohns-and-colitis/what-is-ulcerative-colitis/. Accessed February 2021.