LUCENT-3: Mirikizumab benefits sustained for 4 years in ulcerative colitis

Eli Lilly and Company announced data from the Phase 3 open-label extension study of LUCENT-3, which combines Mirikizumab (Mirikizumab Established as the first and only interleukin-23p19 (IL-23p19) to help patients with moderately to severely active ulcerative colitis (UC) achieve sustained long-term results over 4 years. According to the company's October 7, 2025 press release, these results spanned multiple symptomatic, clinical, endoscopic, histological and quality-of-life measures and included patients who had failed prior biologic or advanced therapies (27%). These data represent the final results from the LUCENT-3 Phase 3 open-label extension study.

Helping patients with ulcerative colitis achieve long-term comprehensive disease control is a major goal because it remains out of reach for many patients. These long-term findings further confirm that militizumab is a highly effective biologic for the treatment of UC, demonstrating sustained clinical, endoscopic and steroid-free remission over four years, as well as improvement in bowel emergencies, which can place a significant burden on patients' lives.

In January 2025, interleukin-23p19 antagonists were approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with moderately to severely active Crohn's disease (CD), expanding the indications for the treatment of UC in 2023. Milizumab approval in CD was based on positive results from the Phase 3 VIVID-1 study in adults with moderately to severely active CD who had an inadequate response, loss of response, or intolerance to corticosteroids, immunomodulators, and/or biologics.

Milizumab in UC was studied in 2 Phase 3 randomized, double-blind, placebo-controlled clinical trials that evaluated the efficacy and safety of militizumab in adults with moderately to severely active UC, including patients who had never tried biologics and refractory patients who had previously failed biologics. LUCENT-3 is a single-arm, long-term Phase 3 open-label extension of LUCENT-1 and LUCENT-2, evaluating the efficacy and safety of militizumab in patients with UC for an additional 3 years of treatment, for a total of 4 years.

As noted in Eli Lilly's press release, inLUCENT-3, the following results were observed after 4 years of full treatment in patients who achieved clinical response within 1 year with milikumab in the Phase 3 LUCENT-2 study:

1. 78% of patients achieved clinical remission without corticosteroids;

2. 78% sustained long-term clinical remission;

3. 81% of endoscopically sustained remissions, defined as an endoscopic score of 0 or 1 (excluding fragility);

4. Inflammatory bowel disease questionnaire shows90% of patients are in remission;

5. 66% of patients achieved histological endoscopic mucosal improvement, which is an important sign of resolution of deep inflammation.

6. 93% reduced the Urgency Numerical Rating Scale (UNRS) by 3 points or more, and 74% achieved UNRS=0 or 1

The researchers noted that the long-term safety profile in patients with moderately to severely active UC was consistent with the known safety profile of militizumab, and no new safety signals were observed. Among patients who completed 1 year of blinded milizumab maintenance therapy in LUCENT-2 and continued in LUCENT-3, 12% reported serious adverse events and 7% discontinued treatment due to adverse events.

With these results, militizumab continues to set the bar high as the first and onlyIL-23p19 with evidence of sustained efficacy and consistent safety in ulcerative colitis over four years.

References:https://www.hcplive.com/view/lucent-3-mirikizumab-omvoh-shows-sustained-benefit-ulcerative-colitis-through-4-years