LUCENT-3 trial open-label extension data show 63.5% of adults with ulcerative colitis administered mirikizumab (Omvoh) who achieved disease clearance at one year maintained composite disease clearance through four years of treatment.
New long-term extension results from Lilly’s phase 3 LUCENT program suggest that a subset of adults with moderately to severely active ulcerative colitis (UC) who reached deep remission on
For clinical trial teams and investigators, the update adds longer-horizon durability data to a treat-to-target discussion that has increasingly shifted from symptom control alone toward composite endoscopic and histologic outcomes.
The data, scheduled for presentation at Digestive Disease Week 2026, come from the open-label LUCENT-3 extension study (NCT03519945) and focus on “disease clearance,” defined as simultaneous symptomatic, endoscopic, and histologic remission.1
“Ulcerative colitis is a lifelong disease, and every person living with the condition deserves a treatment that can deliver strong and durable disease control, not just symptom relief,” Adrienne Brown, executive vice president and president of Lilly Immunology, said in the company statement. "Disease clearance sets that bar higher, and these data show Omvoh-treated patients achieved and sustained it over four years with consistent monthly dosing."
According to Lilly, 63.5% of patients treated with mirikizumab who had achieved disease clearance at 1 year maintained that composite outcome at 4 years in an observed-cases, post hoc analysis.1 At a more stringent threshold requiring endoscopic normalization in addition to symptomatic and histologic remission, 61.3% maintained that status through year 4.
The company also reported more conservative modified nonresponder imputation rates of 49.7% for disease clearance and 42.8% for stringent disease clearance among year-1 responders who sustained those outcomes at year 4.
The broader LUCENT program included LUCENT-1, a randomized, double-blind, placebo-controlled induction trial, and LUCENT-2, a randomized maintenance trial in responders from induction.2 LUCENT-3 is a single-arm, open-label extension that followed patients for an additional 3 years, for up to 4 years of total treatment exposure.1,2
The original phase 3 program enrolled both biologic-naive patients and those with prior biologic or Janus kinase inhibitor failure, reflecting the heterogeneity commonly seen in contemporary UC trial populations.1,2
Mirikizumab is an interleukin-23p19 (IL23p19) antagonist that 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.
In the pivotal phase 3 UC program, the agent improved clinical and endoscopic outcomes compared with placebo, findings that supported subsequent regulatory approvals.2 The drug is now approved in the US for adults with moderately to severely active UC and Crohn disease, and Lilly says it has approvals in 47 countries.1
In the US, labeling includes intravenous induction followed by subcutaneous maintenance, including a single-injection maintenance option for UC.3
Clinically, the emphasis on disease clearance reflects a broader shift in inflammatory bowel disease management. Histologic improvement and endoscopic healing have been associated with better long-term outcomes, although the exact role of composite “disease clearance” endpoints in routine practice and registrational development remains evolving.4
For operations teams, that may have implications for protocol complexity, central reading, biopsy handling, and long-term retention in extension studies, particularly when composite remission requires concordant symptom, endoscopic, and pathology assessments.
Safety findings in LUCENT-3 were described by Lilly as consistent with the established profile of mirikizumab, with no new safety signals observed.1 Among patients who completed 1 year of blinded mirikizumab maintenance in LUCENT-2 and rolled over into LUCENT-3, 12% reported a serious adverse event and 7% discontinued because of an adverse event.
The company said the most common adverse reactions seen across LUCENT-1 and LUCENT-2 were upper respiratory tract infections, injection-site reactions, arthralgia, rash, headache, and herpes viral infection.1 US prescribing information also warns about serious hypersensitivity reactions, infections including tuberculosis risk, and hepatotoxicity.3
The findings should be interpreted cautiously. The disease-clearance analysis was post hoc, and LUCENT-3 was open label without a long-term control arm.1
Observed-case analyses can overestimate durability because they exclude patients who discontinue treatment or have missing data, although Lilly also provided modified nonresponder imputation results that were lower.
Even with those caveats, the dataset adds to the long-term evidence base for IL-23 blockade in UC. Next steps will likely include peer-reviewed publication of the 4-year analyses, further assessment of how disease-clearance endpoints correlate with hospitalization and surgery in prospective cohorts, and results from Lilly’s ongoing combination and pediatric studies listed in the company update.1
