S1446 Efficacy and Safety of Long-Term Mirikizumab Treatment in Patients With Moderate to Severe Crohn’s Disease

Introduction: Mirikizumab (miri), an anti-IL-23p19 antibody, was efficacious and safe as a treatment for moderately-to-severely active Crohn's disease (CD) over 104 weeks in a Phase 2 study (AMAG; NCT02891226). Here we show continued activity through an additional 3 years (up to 6.5 years total) in a long-term extension study, AMAX (NCT04232553). Methods: Data through Jan 20, 2024 are presented for all patients who enrolled in AMAX from AMAG; patients continued on open-label miri 300 mg subcutaneously every 4 weeks. Endoscopy was performed at 3 years in AMAX. Efficacy definitions were: endoscopic response, ≥50% reduction from AMAG baseline in Simple Endoscopic Score for Crohn’s Disease (SES-CD) Total Score; endoscopic remission, SES-CD Total Score ≤4 and ≥2-point reduction from baseline with no subscore >1 for any individual variable; Crohn’s Disease Activity Score (CDAI) response, CDAI decrease from baseline ≥100 points and/or < 150; CDAI remission, CDAI < 150. Data are presented as-observed. Results: 106 patients enrolled in AMAX; at database lock, median miri treatment duration (Q1, Q3) was 5.6 (5.3, 5.9) years. At Week 156 of AMAX, 18 patients (17.0%) had discontinued. For endoscopic results, 17 patients (16.0%) did not yet have data available for week 156. At Week 156 of AMAX, relative to AMAG baseline, the endoscopic response rate was 76.1% (n=54/71) and remission rate was 53.5% (n=38/71). For CDAI, 33 (31%) patients were ongoing but had missing data at Week 156; the CDAI response rate was 96.3% (n=52/54), and CDAI remission rate was 87.3% (n=48/55). Summary safety data in AMAX (see Table 1) showed that treatment emergent adverse events (TEAEs) were reported by 81.1% (n=86) of patients, with 9 (8.5%) patients reporting serious adverse events. Rates of TEAEs of special interest were as follows: any infection/infestation, 54.7% (n=58); opportunistic infections, 3.8% (n=4; 1 candidiasis; 3 herpes zoster [with concomitant azathioprine use in 2 of these cases]); malignancies, 0.9% (n=1 non-melanoma skin cancer [basal cell carcinoma]); and cerebro-cardiovascular events, 0.9% (n=1 bradycardia). Conclusion: Miri demonstrated durable efficacy up to >6 years in patients with moderately-to-severely active CD. Rates of endoscopic and clinical remission were generally maintained from the end of the AMAG maintenance period at Week 52. No unexpected safety events were reported and there were few discontinuations due to adverse events. Table 1. - Summary of Efficacy and Safety Through 156 Weeks in AMAX Endoscopic response 54/71 (76.1) Endoscopic remission 38/71 (53.5) CDAI response 52/54 (96.3) CDAI remission 48/55 (87.3) TEAEMildModerateSevere 86/106 (81.1)28/106 (26.4)50/106 (47.2)8/106 (7.5) Serious adverse events 9/106 (8.5) Deaths 0 Discontinuation due to AEs 2/106 (1.9) AE= adverse event; CDAI= Crohn’s Disease Activity Score; TEAE=treatment emergent adverse event. All data are shown as n/N (%), where N is the number of patients with data available at Week 156 for efficacy, and all patients enrolled from AMAG into AMAX for safety. See Methods for response and remission definitions.

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