Two-Year Efficacy and Safety of Mirikizumab Following 104 Weeks of Continuous Treatment: Interim Results From the LUCENT-3 Open-Label Extension Study

Introduction: Here we present results from the ongoing open-label LUCENT-3 extension study evaluating long-term efficacy and safety of mirikizumab (miri) in patients with moderately-to-severely active ulcerative colitis (UC). Methods: In LUCENT-3, patients received 200mg miri Q4W subcutaneously. Following 104W of continuous miri treatment, we report clinical response and remission, corticosteroid-free (CSF) remission, endoscopic remission, histologic-endoscopic mucosal improvement (HEMI) and histologic-endoscopic mucosal remission (HEMR), symptomatic remission, bowel urgency clinical meaningful improvement (CMI) and remission scores for patients who were W52 responders and remitters, including induction baseline biologic failure status. Symptom scores for abdominal pain, bowel urgency, stool frequency (SF), and rectal bleeding (RB) from induction baseline were recorded for all patients completing W52. Biologic Failed was defined as prior inadequate response, loss of response, or intolerance to biologic therapy or Janus kinase inhibitors; otherwise, patients were categorized as Not Biologic Failed. Safety data were assessed. Results: Among W52 miri responders (N=239), 74.5% demonstrated clinical response at W104. Remission rates at W104 for W52 clinical responders were: 54.0% clinical, 52.7% CSF, 65.3% endoscopic, 47.7% HEMR, 67.8% symptomatic, and 50.2% bowel urgency. Patients achieving HEMI and bowel urgency CMI at W104 were 53.1% and 67.0%, respectively. For W52 miri remitters, 76.6% demonstrated clinical response at W104. Remission rates at W104 for W52 clinical remitters (N=154) were: 65.6% clinical, 64.3% CSF, 77.3% endoscopic, 59.1% HEMR, 74.0% symptomatic, and 51.3% bowel urgency. Patients achieving HEMI and bowel urgency CMI at W104 were 66.2% and 67.3%, respectively. Biologic Failed/Non-failed subgroup data were generally similar (Table 1). Symptom score reductions from induction baseline at W52 were sustained through W104; W52 and W104 scores were respectively: SF: -1.68, -1.79; RB: -1.45, -1.45; bowel urgency: -4.03, -4.44; and abdominal pain: -3.74, -3.91. Severe TEAEs were reported in 4.5% of patients, while 5.2% experienced serious AEs, and 2.8% discontinued treatment due to an AE. Conclusion: These data support the long-term benefit of continuous miri treatment through W104 on clinical, endoscopic, histologic, and symptomatic endpoints, including biologic-failed patients, with no new safety signals identified or deaths reported. Table 1. - LUCENT-3 Response and Remission at 104 Weeks of Continuous Treatment in LUCENT-2 Responders1 and Remitters2 - mITT Population, NRI In Week 52 Responders In Week 52 Remitters Endpoints W104 n=239 % All (95% CI3) n=166 % NBF (95% CI3) n=73 % BF (95% CI3) n=154 % All (95% CI3) n =107 % NBF (95% CI3) n=47 % BF (95% CI3) Clinical Response4 74.5 (68.6, 79.6) 77.1 (70.1, 82.8) 68.5 (57.1, 78.0) 76.6 (69.3, 82.6) 75.7 (66.8, 82.8) 78.7 (65.1, 88.0) Clinical Remission5 54.0 (47.6, 60.2) 56.0 (48.4, 63.4) 49.3 (38.2, 60.5) 65.6 (57.8, 72.6) 67.3 (57.9, 75.4) 61.7 (47.4, 74.2) Symptomatic Remission6 67.8 (61.6, 73.4) 69.9 (62.5, 76.3) 63.0 (51.5, 73.2) 74.0 (66.6, 80.3) 73.8 (64.8, 81.2) 74.5 (60.5, 84.7) Corticosteroid-free Remission7 52.7 (46.4, 59.0) 54.8 (47.2, 62.2) 47.9 (36.9, 59.2) 64.3 (56.5, 71.4) 66.4 (57.0, 74.6) 59.6 (45.3, 72.4) HEMI8 53.1 (46.8, 59.4) 54.2 (46.6, 61.6) 50.7 (39.5, 61.8) 66.2 (58.5, 73.2) 67.3 (57.9, 75.4) 63.8 (49.5, 76.0) HEMR9 47.7 (41.5, 54.0) 48.2 (40.7, 55.7) 46.6 (35.6, 57.9) 59.1 (51.2, 66.5) 59.8 (50.3, 68.6) 57.4 (43.3, 70.5) Endoscopic Remission10 65.3 (59.0, 71.0) 68.7 (61.3, 75.2) 57.5 (46.1, 68.2) 77.3 (70.0, 83.2) 80.4 (71.9, 86.8) 70.2 (56.0, 81.3) Bowel Urgency Remission11 50.2 (43.9, 56.5) 54.2 (46.6, 61.6) 41.1 (30.5, 52.6) 51.3 (43.5, 59.1) 55.1 (45.7, 64.2) 42.6 (29.5, 56.7) Bowel Urgency CMI12 n=224 13 67.0 (60.6, 72.8) n=155 13 71.0 (63.4, 77.5) n=69 13 58.0 (46.2, 68.9) n=147 13 67.3 (59.4, 74.4) n=102 13 68.6 (59.1, 76.8) n=45 13 64.4 (49.8, 76.8) BF=Biofailed; CI=Confidence Interval; ES=Endoscopic Subscore; HEMI=Histologic-endoscopic Mucosal Improvement; HEMR=Histologic-endoscopic Mucosal Remission; mITT=Modified Intent-to-Treat; NBF=Not Biofailed; NRI=Nonresponder Imputation; Not Biologic Failed: failed conventional treatments (i.e., immunomodulators/corticosteroids); may include some participants who were exposed to but did not fail biologic treatment; Biologic Failed: Inadequate response, loss of response, or intolerant to a biologic therapy or the Janus kinase inhibitors for UC. CMI = Clinical Meaningful Improvement, NRS = Numeric Rating Scale.1Responders = (≥30% and 2-point decrease from baseline in the composite clinical endpoint of the sum of endoscopic (ES), stool frequency (SF) and rectal bleeding (RB) subscores, and RB = 0 or 1, or ≥1 pt decrease from baseline).2Remitters = (Mayo Modified Score [MMS] SF = 0 or SF = 1 with ≥ 1-point decrease from baseline; RB = 0; ES = 0 or 1) cohort of LUCENT-2 at W52.3Response confidence intervals are constructed using Wilson method, without continuity correction.4Clinical response: ≥2-point and ≥30% decrease in MMS from baseline; RB=0 or 1 or, RB ≥1-point decrease from baseline.5Clinical remission: SF=0 or SF=1 with ≥1-point decrease in MMS from baseline; RB=0; and ES=0 or 1 (excluding friability).6Symptomatic remission: SF=0 or SF=1 with ≥1-point decrease in MMS from baseline; RB=0.7Corticosteroid-free remission: Defined as clinical remission, and no corticosteroid use for at least 12 weeks prior to Week 52; SF = 0, or SF = 1 with a ≥1-point decrease from induction baseline; RB = 0; ES = 0 or 1 (excluding friability).8HEMI: Endoscopic subscore=0 or 1 (excluding friability) + Geboes≤3.1.9HEMR: Endoscopic subscore=0 or 1 (excluding friability) + Geboes≤2B.0.10Endoscopic remission: ES=0 or 1 (excluding friability); score ranges 0 to 4; a lower score indicates less mucosal damage.11Bowel urgency remission: UNRS=0 or 1.12Bowel urgency CMI: Change from baseline in UNRS≥3 in patients with UNRS≥3 at induction baseline.13In patients who had BU NRS≥3 at induction baseline.