S1727 Mirikizumab Demonstrates Rapid and Sustained Improvements in Bowel Urgency Measures and Clinical Measures in Moderately-to-Severely Active Ulcerative Colitis: 28-Week Results from the Phase 3b LUCENT-URGE Trial

Introduction: LUCENT-URGE is a Phase 3b, open-label, single-arm 28-week (W) study in adults with moderately-to-severely active ulcerative colitis (UC) and bowel urgency (BU, Urgency Numeric Rating Scale [UNRS] ≥3) at baseline treated with mirikizumab (MIRI). Here, we report W28 results from LUCENT-URGE. Methods: Patients (pts) received intravenous MIRI 300 mg at W0, 4 and 8, followed by 200 mg subcutaneous at W12, 16, 20, and 24. Primary objective: UNRS improvement at W12. Secondary objectives: UNRS improvement at W28, Stool Deferral Time (SDT) and Bowel Urgency Frequency (BUF) improvement at W12 and W28, proportion of participants achieving clinical remission and an UNRS score of ≤1 (BU remission) at W12 and W28, and those achieving clinical response and an improvement in UNRS score ≥3 (clinically meaningful improvement [CMI] of UNRS) at W12 and W28. UNRS and BUF were measured using a daily diary where pts recorded the number of times they experienced BU in the past 24 hours, averaged over a 7-day period. The shortest weekly SDT was used. Results: 172 pts were enrolled from 8 countries. Baseline modified Mayo score (MMS; mean ± standard deviation [SD]) was 6.8 ± 1.3, and 64.0% pts had severe disease activity (MMS 7-9). Baseline mean duration of UC was 8.0 years, mean UNRS score was 6.9 and mean BUF was 6.9 times/day. Mean UNRS and BUF improved from baseline (3.6) to W28 (3.8). The proportion of pts with SDT defined as “≥15 minutes or no urgency” was 4.1% at baseline and improved to 29.7% at W28. W12: 36 (20.9%) pts achieved clinical remission, 54 (31.4%) achieved endoscopic remission, and 92 (53.5%) achieved CMI of UNRS. W28: 62 (36.1%) pts achieved clinical remission, 76 (44.2%) achieved endoscopic remission, and 100 (58.1%) achieved CMI of UNRS. 76 (44.2%) pts achieved both clinical response and CMI of UNRS at W12, and 86 (50.0%) pts at W28. W12 and W28: 8 patients (4.7%) and 28 patients (16.3%) achieved both clinical remission and BU remission, respectively. The safety profile of MIRI in LUCENT-URGE was consistent with previous studies, with no death reported and similar frequency of treatment-emergent adverse events (TEAEs). Most common TEAEs: ulcerative colitis exacerbation (5.2%) and upper respiratory tract infection (5.2%). Conclusion: MIRI showed an early and sustained improvement on BU severity, frequency and stool deferral time through W28 in LUCENT-URGE. MIRI consistently improved clinical outcomes in pts with moderately-to-severely active UC.