Omvoh (mirikizumab-mrkz) is the first and only IL-23p19 antagonist to show four years of sustained, corticosteroid-free comprehensive patient outcomes in ulcerative colitis – Eli Lilly

New data from Eli Lilly and Company showed Omvoh (mirikizumab-mrkz) is the first and only interleukin-23p19 (IL-23p19) to help patients with moderately to severely active ulcerative colitis (UC) achieve sustained, long-term outcomes through four years. The results were seen across multiple symptomatic, clinical, endoscopic, histologic and quality-of-life measures, including among patients who had previously failed a biologic or advanced therapy (27%). These data are the final results from the LUCENT-3 Phase III open-label extension study and will be presented at United European Gastroenterology (UEG) Week, taking place in Berlin.

“Helping people with ulcerative colitis achieve long-term comprehensive disease control is a major goal for gastroenterologists, as it has remained out of reach for many patients,” said Bruce Sands, M.D., M.S., 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. “These long-term findings reinforce mirikizumab as a highly effective biologic for UC management, showing sustained clinical, endoscopic and steroid-free remission over four years, and improvement in bowel urgency, which can present a significant burden on patients’ lives.”

In LUCENT-3, the following results were observed after four years of total treatment among those who achieved clinical remission with Omvoh at one year in the Phase III LUCENT-2 study:

i) 78% achieved corticosteroid-free clinical remission

ii) 78% sustained long-term clinical remission

iii) 81% sustained endoscopic remission, defined as an endoscopic subscore of 0 or 1 (excluding friability)

iv) 90% achieved remission on the Inflammatory Bowel Disease Questionnaire (IBDQ)

v) 66% achieved histological-endoscopic mucosal improvement, an important marker of deep inflammation resolution

vi) 93% achieved a 3 or more-point reduction on the Urgency Numeric Rating Scale (UNRS), and 74% achieved UNRS = 0 or 1. UNRS is the patient-centric scale of 0-10 that evaluates bowel urgency severity, with 0 being no bowel urgency and 10 being worst possible bowel urgency.

These data were also evaluated using a modified non-responder imputation (mNRI) – see below in the About the LUCENT Clinical Trial Program section. These results build upon previously disclosed first-of-their-kind long-term results for Omvoh in both UC and Crohn’s disease.

The long-term safety profile in patients with moderately to severely active UC was consistent with the known safety profile of Omvoh with no new safety signals observed. Of patients who completed one year of blinded Omvoh maintenance therapy in LUCENT-2 and continued on to LUCENT-3, 12% reported a serious adverse event, while 7% discontinued treatment due to an adverse event.

“With these results, Omvoh continues to set a high standard as the first and only IL-23p19 with evidence of sustained efficacy and consistent safety in ulcerative colitis over four years,” said Mark Genovese, M.D., senior vice president of Lilly Immunology development. “Lilly is shaping the future of IBD care to make life better for patients by redefining what’s possible in terms of steroid-free, long-lasting, comprehensive disease control, including durable clinical and endo-histologic remission and relief of disruptive symptoms like bowel urgency.”

Beyond ongoing UC studies, including in pediatric patients (NCT05784246), Lilly is advancing combination studies of mirikizumab aimed at delivering breakthrough induction efficacy while maintaining long-term remission and safety. These include studies with eltrekibart (NCT06598943), a monoclonal antibody that targets neutrophil-driven inflammation, and with LY4268989 (MORF-057) (NCT07186101), an oral α4β7 integrin inhibitor. Lilly is also advancing novel science to uncover the potential of incretins in immunology and has initiated the COMMIT-UC (NCT06937086) and COMMIT-CD (NCT06937099) trials evaluating the concomitant use of mirikizumab with an incretin-based therapy.

Omvoh has received regulatory approvals for the treatment of moderately to severely active UC and moderately to severely active Crohn’s disease in adults and has been approved in 44 countries around the world.

About the LUCENT Clinical Trial Program
Omvoh was studied in two Phase III randomized, double-blind and placebo controlled clinical trials that evaluated the efficacy and safety of mirikizumab in adults with moderately to severely active ulcerative colitis (UC) and included patients who had never tried a biologic (biologic-naïve) and harder-to-treat patients who had previously taken a biologic that failed. Patients (N=1279) were randomized 3:1 to receive Omvoh 300 mg IV or placebo IV Q4W at Weeks 0, 4, and 8 in the blinded induction study (LUCENT-1). Omvoh responders from LUCENT-1 (N=581) were re-randomized 2:1 to receive Omvoh 200 mg or placebo subcutaneous (SC) Q4W for 40 weeks in the blinded maintenance study (LUCENT-2) (52 weeks of continuous therapy). LUCENT-1 and LUCENT-2 studies included those who had inadequate response, loss of response, or failed to tolerate any of the following: corticosteroids, immunomodulators (6-mercaptopurine and azathioprine), biologic therapy (TNF blocker, vedolizumab) or Janus kinase inhibitors (JAKi, tofacitinib). Additionally, 41% of patients in LUCENT-1 had failed at least one biologic, 3% had failed a JAKi and 57% were biologic and JAKi-naïve.

LUCENT-3, the single-arm long-term Phase III open-label extension of LUCENT-1 and LUCENT-2, evaluated the efficacy and safety of mirikizumab in patients with UC for an additional three years of treatment (up to four years total). Using a mNRI analysis to handle discontinuation and missing data, response rates among Week 52 mirikizumab remitters for major efficacy endpoints included: corticosteroid-free remission (62%), clinical remission (62%), endoscopic remission (66%), IBDQ remission (73%), histologic-endoscopic mucosal improvement (53%), 3 or more-point reduction on UNRS (75%) and UNRS = 0 or 1 (60%).