Eli Lilly's mirikizumab, already FDA-approved for ulcerative colitis, has shown promising long-term efficacy in both ulcerative colitis and Crohn's disease. Data from the LUCENT-3 and VIVID-2 clinical trials, presented at the 2024 American College of Gastroenterology (ACG) Annual Meeting, highlight the drug's ability to maintain remission and provide sustained benefits over several years.
Long-Term Remission in Ulcerative Colitis
The LUCENT-3 trial, a continuation of the LUCENT clinical trial program, evaluated the long-term effects of mirikizumab in patients with ulcerative colitis. The study found that among participants who achieved clinical remission with mirikizumab at one year in the LUCENT-2 trial, 81% maintained long-term clinical remission after an additional two years of treatment, totaling up to three years. These findings, published in the journal Inflammatory Bowel Diseases, suggest that mirikizumab can provide durable intestinal healing and relief from key symptoms.
Anabela Cardoso, MD, senior vice president for Lilly Immunology Medical Affairs, noted that mirikizumab provided sustained benefit across symptomatic, clinical, endoscopic, and histologic endpoints for up to three years, regardless of previous failure to TNF inhibitors, tofacitinib, or other biologics. This is particularly significant as current therapies often fail to achieve or maintain clinical remission, leaving patients with difficult-to-manage symptoms.
Sustained Remission in Crohn's Disease
Data from the VIVID-2 clinical trial, presented at ACG 2024, demonstrated the long-term efficacy of mirikizumab in treating moderately to severely active Crohn's disease. The study showed that 96% of participants treated with mirikizumab had a clinical response measurable by the Crohn's Disease Activity Index (CDAI), and 87% were in clinical remission based on the CDAI for up to five years.
Cardoso explained that achieving and sustaining CDAI remission is a key goal for healthcare providers treating Crohn's disease. The VIVID-2 trial results reinforce the efficacy and safety of mirikizumab, demonstrating that patients who achieve remission with the drug can sustain long-term endoscopic remission for up to five years.
Mechanism of Action and Clinical Significance
Mirikizumab is an interleukin-23p19 (IL-23p19) antagonist, selectively binding to the p19 subunit of the IL-23 protein and inhibiting its interaction with the IL-23 receptor. This mechanism reduces the effects of IL-23, a protein that can activate the immune system, thereby reducing inflammation in ulcerative colitis and Crohn's disease.
Inflammation from these conditions can lead to disruptive symptoms, including bowel urgency, which can significantly decrease health-related quality of life. Mirikizumab offers a potential solution by providing long-standing remission and relieving disease burden without the need for corticosteroids.
Expert Commentary
Rudolph Bedford, MD, a board-certified gastroenterologist at Providence Saint John's Health Center, emphasized the importance of having more drugs available for treating IBD. He noted that while tumor necrosis factors (TNFs) have been used, they often lose effectiveness over time. Bedford also expressed interest in seeing more head-to-head trials of IL-23 drugs to determine the best-in-class medications for patients.
