Mirikizumab Sustains CDAI, PRO Remission for Crohn Disease, Shown in Phase 2 Data at ACG 2023

Monika Fisher, MD, MSc

Credit: Indiana University Health

New phase 2 data are shining light on the safety and efficacy of mirikizumab in patients with moderately to severely active Crohn disease (CD), highlighting its ability to sustain Crohn Disease Activity Index (CDAI) and patient-reported outcome (PRO) remission through week 104.

Presented in an abstract at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting in Vancouver, presenter Monika Fisher, MD, MSc, professor of medicine at Indiana University, reported on data from the phase 2 SERENITY trial, which showed sustained CDAI and PRO remission among participants treated with mirikizumab during the maintenance and extension periods, regardless of treatment or achievement of endoscopic response at week 12.¹

Data through 12 weeks were presented at ​the Digestive Disease Week medical conference in San Diego, California on May 21, 2019, which showed rates of endoscopic response and remission were significantly greater among patients receiving mirikizumab compared to those receiving placebo.² The 104-week extension of the randomized, controlled, phase 2 trial further assessed the safety and efficacy of mirikizumab in patients with moderately to severely active CD.¹

Investigators enrolled patients with a diagnosis of CD > 3 months before the start of the study who demonstrated an inadequate response or intolerance to at least 1 conventional treatment or prior exposure to at least 1 biologic agent. Patients were required to have moderately to severely active disease, defined as stool frequency ≥ 4 per day and/or abdominal pain ≥ 2, and a Simple Endoscopic Score for Crohn’s Disease (SES-CD) score ≥ 7 for patients with ileal-colonic disease or ≥ 4 for patients with isolated ileal disease.¹

In total, 191 participants were enrolled in the study and randomized in a 2:1:1:2 ratio to receive mirikizumab 1000 mg (n = 64), mirikizumab 600 mg (n = 32), mirikizumab 200 mg (n = 31), or placebo (n = 64) intravenously every 4 weeks for a total of 8 weeks. At week 12, 68.5% of patients who received mirikizumab achieved ≥1 point improvement in SES-CD and were rerandomized 1:1 into double-blind maintenance to continue intravenous treatment (n = 41) or switch to 300mg mirikizumab subcutaneous treatment (n = 46) through week 52 during the study’s maintenance period. Mirikizumab endoscopic non improvers and placebo patients received mirikizumab 1000 mg intravenous dosing.¹

Clinical endpoints for CDAI remission, defined as CDAI score < 150, and PRO remission, defined as stool frequency < 2.5 and abdominal pain < 1, were assessed at weeks 52 and 104. At week 52, 74 patients experiencing clinical benefit were assigned to mirikizumab 300 mg subcutaneous during the extension period through week 104. Of this group, 6 discontinued between week 52 and week 104 due to adverse events (n = 1), lack of efficacy (n = 2), loss of follow-up (n = 1), and withdrawal by subject (n = 2), with 68 participants completing treatment.¹

Upon analysis, CDAI remission was maintained from week 52 through week 104 in both week 12 endoscopic improvers and non improvers. Among patients who received intravenous mirikizumab treatment, 39% achieved CDAI remission at week 52 and 66.7% achieved CDAI remission at week 104. In the subcutaneous cohort, 56.5% of patients achieved CDAI remission at week 52 compared to 61.0% at week 104.¹

Investigators pointed out PRO remission was also maintained from week 52 through week 104 in both endoscopic improvers and non improvers. PRO remission was achieved by 46.3% of patients receiving intravenous mirikizumab treatment at week 52 and 63.6% at week 104. In the subcutaneous cohort, 45.7% of patients achieved PRO remission at week 52 compared to 46.3% at week 104.¹

“CDAI and PRO remission were sustained through W104, with no differences observed in patients who received either IV-C and SC mirikizumab treatments during maintenance and continued into the extension period,” concluded investigators.¹

References:

1. Kaser A, Sands B, Protic M, et al. P2109 - Efficacy and Safety of Mirikizumab in Patients With Crohn’s Disease: 104-Week Extension Results From a Phase 2 Randomized Controlled Trial. Paper presented at: ACG 2023 Annual Scientific Meeting. Vancouver, BC, Canada. October 20 – 25, 2023.
2. Eli Lilly and Company. Lilly's Mirikizumab Met Primary Endpoint and Key Secondary Endpoints in Phase 2 Study, Including Reductions of Gastrointestinal Lesions. News Release. May 21, 2019. Accessed October 24, 2023. https://investor.lilly.com/news-releases/news-release-details/lillys-mirikizumab-met-primary-endpoint-and-key-secondary