Omvoh Achieves Long-Term Remission, Symptom Improvement for Ulcerative Colitis, Crohn Disease in Phase III Trials

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A pair of multiyear Phase III trials show that Eli Lilly's Omvoh (mirikizumab) produced stable, long-term remission and improved symptoms in patients with ulcerative colitis (UC) and Crohn disease (CD) with consistent safety profiles, according to data presented at the American College of Gastroenterology Annual Meeting.^1-3

Omvoh, an interleukin-23p19 (IL23p19) antagonist, selectively attaches to the p19 subunit of IL-23 to interfere with its interaction with the IL-23 receptor. The drug was approved in October 2023 as the first and only IL23p19 antagonist indicated to treat adults with moderately to severely active UC.⁴

"Mirikizumab is the first and only IL23p19 antagonist to report multi-year, long-term sustained efficacy data in both ulcerative colitis and Crohn's disease," Mark Genovese, MD, senior vice president of Lilly Immunology development, said in a press release. "This achievement reflects our commitment to help people with immune system conditions sustain long-standing remission and relieve disease burden."¹

The ongoing, long-term, open-label, Phase III LUCENT-3 (NCT03519945) trial is an extension of the LUCENT-1 and LUCENT-2 trials, and is analyzing the efficacy and safety of Omvoh in patients with UC for up to three years.² The induction LUCENT-1 trial and maintenance LUCENT-2 trial were both randomized, double-blind, placebo-controlled studies that enrolled patients who showed inadequate response, loss of response, or who failed to tolerate corticosteroids, immunomodulators, biologic therapies, or Janus kinase inhibitors. Patients administered Omvoh showed a sustained benefit across symptomatic, clinical, endoscopic, and histologic endpoints for up to three years, regardless of prior treatment failure with TNF inhibitors, tofacitinib, or other biologic therapies.

An analysis following two additional years of treatment for up to three years total showed that among patients who achieved clinical remission with Omvoh after one year in the LUCENT-2 trial, 81% maintained long-term clinical remission; 82% achieved long-term endoscopic remission; 72% experienced mucosal healing; 79% achieved corticosteroid-free clinical remission; and patients showed sustained, clinically meaningful improvements in symptom score decrease for bowel urgency (-4.72). In terms of safety, 7.4% of patients experienced serious adverse events (AEs), with 5.3% discontinuing treatment as a result. The long-term safety profile in the trial was consistent with the previously established profile of Omvoh with no new safety signals reported.

The ongoing, multicenter, open-label, Phase III VIVID-2 trial (NCT04232553)³ is a long-term extension of the SERENITY (NCT02891226)⁵ and VIVID-1 (NCT03926130)⁶ clinical trials. Investigators analyzed the efficacy and safety of Omvoh in patients with CD for up to five years. The Phase II, multicenter, randomized, parallel-arm, double-blind, placebo-controlled SERENITY trial evaluated the safety and efficacy of Omvoh in patients with moderately to severely active CD. The Phase III, randomized, double-blind, treat-through VIVID-1 trial compared the safety and efficacy of Omvoh vs. placebo and active control Stelara (ustekinumab) in adult patients with moderately to severely active CD.

Results from VIVID-2 show that patients with moderately to severely active CD administered Omvoh were able to maintain high rates of clinical and endoscopic remission over time. An observed case analysis following an additional three years of treatment for up to five years total show 96% of patients administered Omvoh achieved clinical response as per the Crohn's Disease Activity Index (CDAI); 87% were in clinical remission as measured by CDAI; 76% achieved endoscopic response; and 54% achieved endoscopic remission.

In terms of safety, 8.5% of patients enrolled in VIVID-2 reported a serious AE and 1.9% discontinued treatment because of an AE. The long-term profile of Omvoh was found consistent with the previously established profile of the drug in patients with moderately to severely active CD.

"Despite continued advances, people living with ulcerative colitis and Crohn's disease are still seeking treatments that can address difficult-to-manage symptoms such as bowel urgency, and provide lasting results over time," Bruce Sands, MD, MS, Dr. Burrill B. Crohn Professor of Medicine and chief of the Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, said in a press release. "These multi-year data show mirikizumab is a targeted therapy that can provide intestinal healing over time and improvement in key symptoms that matter most to patients."¹

References

1. Lilly's mirikizumab is first and only IL23p19 antagonist to report long-term, multi-year, sustained efficacy and safety data for both ulcerative colitis and Crohn's disease. News release. Eli Lilly. October 28, 2024. Accessed October 28, 2024. https://investor.lilly.com/news-releases/news-release-details/lillys-mirikizumab-first-and-only-il23p19-antagonist-report-long

2. A Study to Evaluate the Long-Term Efficacy and Safety of Mirikizumab in Participants With Moderately to Severely Active Ulcerative Colitis (LUCENT 3). ClinicalTrials.gov. Updated October 15, 2024. Accessed October 28, 2024. https://clinicaltrials.gov/study/NCT03519945

3. A Long-term Extension Study of Mirikizumab (LY3074828) in Participants With Crohn's Disease (VIVID-2). ClinicalTrials.gov. Updated October 15, 2024. Accessed October 28, 2024. https://clinicaltrials.gov/study/NCT04232553

4. FDA Approves Lilly's Omvoh™ (mirikizumab-mrkz), A First-in-Class Treatment for Adults with Moderately to Severely Active Ulcerative Colitis. News release. Eli Lilly. October 26, 2023. Accessed October 28, 2024. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-omvohtm-mirikizumab-mrkz-first-class

5. A Study of Mirikizumab (LY3074828) in Participants With Active Crohn's Disease (SERENITY). ClinicalTrials.gov. Updated August 30, 2022. Accessed October 28, 2024. https://clinicaltrials.gov/study/NCT02891226

6. A Study of Mirikizumab (LY3074828) in Participants With Crohn's Disease (VIVID-1). ClinicalTrials.gov. Updated December 8, 2023. Accessed October 28, 2024. https://clinicaltrials.gov/study/NCT03926130