P0775Efficacy and safety of mirikizumab as maintenance therapy in East Asian patients with moderately to severely active ulcerative colitis: subpopulation results from the phase 3 Lucent-2 study

Background Mirikizumab (miri), a humanized IgG4-variant monoclonal antibody that specifically binds to IL-23p19 subunit, demonstrated benefits in patients (pts) with ulcerative colitis (UC) in phase (Ph)3 induction (LUCENT-1) and maintenance (LUCENT-2) studies.1 Here we report the efficacy and safety results of the East Asian (EA) subpopulation (China, Japan and South Korea) from the Ph3 LUCENT-2 study (NCT03524092, a double-blind, randomized withdrawal maintenance study enrolling pts who responded to miri induction therapy from LUCENT-1). Methods After 12-week induction therapy, miri clinical responders were re-randomized in a 2:1 ratio to receive blinded miri 200 mg or placebo (PBO) subcutaneously every four weeks for 40 weeks (EA primary efficacy population N = 165). Randomization was stratified by biologic agent/tofacitinib failed status, induction remission status, and baseline glucocorticoid (GC) use. The primary objective was to test the hypothesis that miri was superior to PBO in achieving clinical remission at Week 40 (W40). Key secondary endpoints included alternate clinical remission, GC-free remission, endoscopic remission, histologic-endoscopic mucosal remission (HEMR), improvement in bowel urgency, bowel urgency remission (BUR), and maintenance of clinical remission. Analyses in the EA subpopulation were descriptive. Results Baseline characteristics were generally balanced across groups, including the proportion of baseline GC/immunomodulator use, biologic agent/tofacitinib failure status, and pancolitis. At W40, a greater proportion of pts treated with miri achieved clinical remission (50.9% vs. 18.9%; Δ = 31.6 [95% confidence interval (CI) 17.3, 46.0]) and alternate clinical remission (54.5% vs. 18.9%; Δ = 35.3 [95%CI 21.0, 49.7]). Miri also demonstrated improvements in other key secondary endpoints compared to placebo at W40, including endoscopic remission (58.9% vs. 20.8%; Δ = 38.1 [95%CI: 23.9, 52.4]), GC-free remission (46.4% vs. 17.0%; Δ = 28.6 [95%CI: 14.7, 42.5]), HEMR (45.5% vs. 15.1%; Δ = 31.2 [95%CI: 18.0, 44.3]), improvement in bowel urgency (-3.92 vs. -2.39; Δ = -1.52 [95%CI: -2.21, -0.84]), BUR (45.0% vs. 18.0%; Δ = 24.8 [95%CI: 10.1, 39.6]), and maintenance of clinical remission (62.8% vs. 25.0%; Δ = 36.9 [95%CI: 12.5, 61.4]). The frequencies of treatment-emergent adverse events (AE) were similar between groups, with fewer serious AE and discontinuations due to AE in the miri group. Conclusion Miri demonstrated favorable efficacy and safety profile for maintenance in EA pts who responded to miri induction therapy, aligning with outcomes observed in the overall LUCENT-2 population and supporting benefits of miri treatment in the EA UC pts. Reference: 1. Geert D’Haens, Marla Dubinsky, Taku Kobayashi, et al. Mirikizumab as Induction and Maintenance Therapy for Ulcerative Colitis. N Engl J Med. 2023 Jun 29;388(26):2444-2455. Conflict of interest: Ran, Zhihua: No conflict of interest Miao, Yinglei: No conflict of interest Wang, Yufang: No conflict of interest Ding, Xueli: No conflict of interest Zhong, Jie: No conflict of interest Chen, Chunxiao: No conflict of interest Kobayashi, Taku: Grant: AbbVie, Alfresa Pharma, Bristol Myers Squibb, Celtrion, EA Pharma, Gilead Sciences, Kyorin Pharmaceutical, Miyarisan, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Pfizer, Sekisui Medical, Takeda, Zeria Pharmaceutical Personal Fees: AbbVie, Alfresa Pharma, Alimentiv, Bristol Myers Squibb, Celltrion, Covidien, EA Pharma, Eli Lilly, Ferring Pharmaceuticals, Galapagos, Gilead Sciences, Janssen, JIMRO, Kissei Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, MSD, Nippon Kayaku, Pfizer, Sekisui Medical, Takeda Pharmaceutical, Zeria Pharmaceutical Tang, Dan: Employee and stockholder of Eli Lilly and Company Qian, Chenxi: Employee and stockholder of Eli Lilly and Company Yu, Jiao: Employee and stockholder of Eli Lilly and Company