P4357 - Early Symptomatic Improvement With Mirikizumab Induction Therapy in Patients With Moderately to Severely Active Crohn’s Disease: Results From the Phase 3 VIVID-1 Study

Bruce E.. Sands, MD, FACG¹, Minhu Chen, ², Silvio Danese, MD, PhD³, Monika Fischer, MD, MS⁴, Tadakazu Hisamatsu, MD, PhD⁵, Sami Hoque, MD⁶, Laurent Peyrin-Biroulet, MD, PhD⁷, Frank Seibold, ⁸, Frederick Durand, ⁹, Zhantao Lin, PhD⁹, Michelle Lopes, ⁹, Nathan Morris, ⁹, Emily Hon, ⁹, Geert R. D'Haens, MD, PhD^10
1Icahn School of Medicine at Mount Sinai, New York, NY; ²First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China; ³Humanitas Clinical and Research Center - IRCCS, Rozzano and Humanitas University, Pieve Emanuele, Milan, Lombardia, Italy; ⁴Indiana University, Indianapolis, IN; ⁵Kyorin University School of Medicine, Tokyo, Tokyo, Japan; ⁶Barts Health NHS Trust, London, England, United Kingdom; ⁷INFINY Institute, FHU-CURE, INSERM NGERE, Nancy University Hospital, Vandœuvre-lès-Nancy, Lorraine, France; McGill University Health Centre, Montreal, QC, Canada, Nancy, Lorraine, France; ⁸Crohn-Colitis Zentrum, Hochhaus Lindenhofspital, Canton, Bern, Switzerland; ⁹Eli Lilly and Company, Indianapolis, IN; ¹⁰Amsterdam University Medical Center, Amsterdam, Limburg, Netherlands

Introduction: Mirikizumab (miri), an anti-IL-23p19 antibody, demonstrated robust efficacy in improving clinical, endoscopic, and inflammatory biomarker endpoints, and an acceptable safety profile for patients (pts) with Crohn’s disease (CD) in the Phase 3 VIVID-1 study. We investigated the onset of symptomatic improvement and safety of miri as induction therapy through Week 12 (W12) for pts with CD.

Methods: In VIVID-1, 1065 pts had moderately to severely active CD (unweighted daily average stool frequency (SF) ≥4 [loose and watery stools defined as Bristol Stool Scale Category 6 or 7] AND/OR unweighted daily average abdominal pain (AP) ≥2 at baseline) and prior failure to biologic and/or conventional therapy. Pts were randomized in a 6:3:2 ratio to receive miri (single 900mg intravenous (IV) dose at W0, W4, and W8 followed by a subcutaneous (SC) dose of 300mg at W12 and then every 4 weeks), ustekinumab (uste) (6mg/kg IV at W0 and 90mg SC dose at W8 and then every 8 weeks), or placebo (PBO). This analysis compared clinical response by Patient Reported Outcome (PRO) (30% decrease in SF and/or AP with neither score worse than W0), clinical remission by PRO (SF≤3 and not worse than W0 and AP ≤1 and no worse than W0), change from baseline (CFB) in SF, and in AP up to W12 in miri/PBO randomized patients.

Results: Baseline characteristics were balanced across the miri (N=579) and PBO (n=199) treatment groups. A greater proportion of the pts on miri achieved clinical response by PRO at W4, W6, W8, and W12, and clinical remission by PRO at W6, W8, and W12 vs PBO. Miri resulted in significant improvements in SF at W6, W8, and W12, and in AP at W4, W6, W8, and W12 vs PBO (Table). The overall safety was consistent with the known safety profile of miri. Most common treatment-emergent adverse events (TEAEs) during induction period in miri-treated pts: COVID-19, anemia, and headache. There were lower frequencies of SAEs (miri: 5.9%, PBO: 9.0%) and discontinuations due to adverse events (miri: 2.4%, PBO:4.7%) in miri-treated pts vs PBO. There were no malignancies, no major adverse cardiovascular events (MACEs), no Hy’s law cases or deaths in the miri arm up to W12. One death was reported in the induction period in the PBO group.

Discussion: In pts with moderately to severely active CD, miri induction was associated with higher rates of clinical response, clinical remission and greater improvement in AP as early as W4, SF as early as W6 vs PBO. Increasing treatment effect was observed through W12.


Disclosures:


Bruce E.. Sands, MD, FACG¹, Minhu Chen, ², Silvio Danese, MD, PhD³, Monika Fischer, MD, MS⁴, Tadakazu Hisamatsu, MD, PhD⁵, Sami Hoque, MD⁶, Laurent Peyrin-Biroulet, MD, PhD⁷, Frank Seibold, ⁸, Frederick Durand, ⁹, Zhantao Lin, PhD⁹, Michelle Lopes, ⁹, Nathan Morris, ⁹, Emily Hon, ⁹, Geert R. D'Haens, MD, PhD¹⁰. P4357 - Early Symptomatic Improvement With Mirikizumab Induction Therapy in Patients With Moderately to Severely Active Crohn’s Disease: Results From the Phase 3 VIVID-1 Study, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.