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- EliLilly

Mirikizumab is an interleukin-23p19 (IL23p19) antagonist that selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. Inflammation due to the overactivation of the IL-23 pathway plays a critical role in pathogenesis of UC and Crohn's disease. Inflammation from UC and Crohn's disease can lead to disruptive symptoms, including bowel urgency, that can result in decreased health-related quality of life and potentially irreversible complications for patients if left untreated. Mirikizumab is approved in the United States (U.S.) for the treatment of moderately to severely active UC in adults and is under review with the FDA for moderately to severely active Crohn's disease.

"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," said Mark Genovese, M.D., senior vice president of Lilly Immunology development. "This achievement reflects our commitment to help people with immune system conditions sustain long-standing remission and relieve disease burden."

Long-Term Data in Adults with UC; In LUCENT-3, mirikizumab helped patients with moderately to severely active UC achieve long-term outcomes, including histologic-endoscopic mucosal remission, defined as mucosal healing. Mirikizumab also 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. Among those who achieved clinical remission with mirikizumab at one year in the LUCENT-2 study, the following results were achieved based upon observed case analysis after an additional two years of treatment (up to three years total):  i. 81% of patients maintained long-term clinical remission ii. 82% achieved long-term endoscopic remission iii. 72% had mucosal healing iv. 79% achieved corticosteroid-free clinical remission Patients demonstrated a sustained clinically meaningful improvement in symptom score reduction for bowel urgency (-4.72)

Among patients receiving mirikizumab in the LUCENT-3 study, 7.4% of patients reported a serious adverse event (AE), while 5.3% discontinued treatment due to an AE. The long-term safety profile in patients with moderately to severely active UC was consistent with the already known safety profile of mirikizumab. These data were recently published in Inflammatory Bowel Diseases. 

Long-Term Data in Adults with Crohn's Disease; New data from patients in the Phase II program who enrolled into the VIVID-2 long-term extension study showed that patients with moderately to severely active Crohn's disease treated with mirikizumab maintained high rates of clinical and endoscopic remission over time. The following results were achieved based upon observed case analysis after an additional three years of treatment (up to five years total): i. 96% of patients had clinical response as measured by the Crohn's Disease Activity Index (CDAI)ii. 87% were in clinical remission as measured by CDAI iii. 76% had endoscopic response, iv. 54% of patients were in endoscopic remission

"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," 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 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." 

Among these patients who enrolled into the VIVID-2 long-term extension study, 8.5% reported a serious AE and 1.9% discontinued treatment due to an AE. The long-term safety profile in patients with moderately to severely active Crohn's disease was consistent with the already known safety profile of mirikizumab.  

Omvoh (mirikizumab-mrkz) was approved by the FDA in October 2023 as the first IL23p19 antagonist for the treatment of moderately to severely active UC in adults and is also approved in 44 countries around the world. Lilly submitted marketing applications for mirikizumab in Crohn's disease around the globe, including in the U.S., Canada, Europe, Japan and China. Additional global regulatory submissions are planned.

Additionally, Lilly has a combination study in UC with mirikizumab and eltrekibart, a humanized monoclonal antibody that binds to the seven ligands that signal through the CXCR1 and CXCR2 chemokine receptors involved in neutrophil movement to sites of inflammation (NCT06598943). There are also ongoing studies in both UC (NCT05611671) and Crohn's disease (NCT06226883) with MORF-057, a selective oral small molecule alpha-4/beta-7 integrin inhibitor that may improve outcomes and expand treatment options for people with IBD.

  About the Mirikizumab Ulcerative Colitis Program; Mirikizumab was studied in two, Phase III clinical trials which 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. The induction LUCENT-1 and maintenance LUCENT-2 studies were randomized, double-blind, and placebo-controlled and 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 ongoing long-term Phase III extension of LUCENT-1 and LUCENT-2 evaluated the efficacy and safety of mirikizumab in patients with UC for up to three years. Using a modified non-responder imputation analysis to handle discontinuation and missing data, among Week 52 mirikizumab remitters, 70% maintained long-term clinical remission at Week 152, and response rates for major efficacy endpoints (including endoscopic remission, histologic-endoscopic mucosal remission, corticosteroid-free remission and clinical response) ranged from 63% to 85%.

About the Mirikizumab Crohn's Disease Program ;VIVID-1 was a Phase III, randomized, double-blind, treat-through study that evaluated the safety and efficacy of mirikizumab compared with placebo and an active control (ustekinumab) in adults with moderately to severely active Crohn's disease. Patients randomized to mirikizumab were administered 900 mg of mirikizumab intravenously every four weeks from Week 0-12, then 300 mg subcutaneously every four weeks from Weeks 12-52. In this study, 49% of patients taking mirikizumab or placebo had experienced a prior biologic failure.

SERENITY, the Phase II, multi-center, randomized, parallel-arm, double-blind, placebo-controlled trial was designed to assess the safety and efficacy of mirikizumab in patients with moderately to severely active Crohn's disease. At baseline, participants were randomized with a 2:1:1:2 allocation across four treatment arms (placebo, mirikizumab 200 mg, mirikizumab 600 mg and mirikizumab 1000 mg). The primary endpoint was endoscopic response as determined by the proportion of participants achieving at least 50% reduction from baseline on the Simple Endoscopic Score for Crohn's Disease (SES-CD) at Week 12. In May 2019, Lilly reported Phase 2 results showing more patients with moderate to severe Crohn's disease receiving mirikizumab compared with placebo achieved clinical response and remission at 12 weeks. Overall, the safety profile at 12 weeks was consistent with that of mirikizumab in studies of ulcerative colitis and with the IL23p19 class.

VIVID-2, the ongoing long-term Phase III extension of SERENITY and the VIVID-1 study, evaluated the efficacy and safety of mirikizumab in patients with Crohn's disease for up to five years. Using a modified non-responder imputation analysis to handle discontinuation and missing data, 61% and 44% achieved endoscopic response and endoscopic remission, respectively, at Week 156. In addition, 79% and 72% achieved clinical response and clinical remission, respectively, at Week 156.

Citation: "Three-Year Efficacy and Safety of Mirikizumab Following 152 Weeks of Continuous Treatment for Ulcerative Colitis: Results From the LUCENT-3 Open-Label Extension Study"- Bruce E Sands, MD, Geert D’Haens, MD, PhD, David B Clemow, PhD, Peter M Irving, MA, MD, FRCP, Jordan T Johns, PhD, Theresa Hunter Gibble, PhD, Maria T Abreu, MD, Scott D Lee, MD, Tadakazu Hisamatsu, MD, PhD, Taku Kobayashi, MD, PhD et al., Inflammatory Bowel Diseases, izae253, https://doi.org/10.1093/ibd/izae253.