P3231 - 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

Silvio Danese, MD, PhD¹, Axel Dignass, MD, PhD², David Laharie, ³, Jimmy Limdi, MD⁴, Radoslaw Kempinski, MD, PhD⁵, James D. Lewis, MD⁶, Ziad Younes, MD⁷, Erica R. Cohen, MD⁸, Karla Alaka, ⁹, William J. Eastman, ⁹, Tian Tian, ⁹, Isabel Redondo, MD⁹, David T. Rubin, MD¹⁰, Marla C. Dubinsky, MD¹¹
1Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, Milan, Lombardia, Italy; 2Agaplesion Markus Hospital, Frankfurt, Hessen, Germany; 3CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology Department; Université de Bordeaux, Pessac, Aquitaine, France; 4Northern Care Alliance NHS Foundation Trust and University of Manchester, Manchester, England, United Kingdom; 5Wrocław Medical University, Wrocław, Lubelskie, Poland; 6Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; 7Gastroenterology Center of the MidSouth PC, Germantown, Germantown, TN; 8Capital Digestive Care, Chevy Chase, Maryland, MD, USA, Chevy Chase, MD; 9Eli Lilly and Company, Indianapolis, IN; 10University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA, Chicago, IL; 11Susan and Leonard Feinstein IBD Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA, New York, NY

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 (Table). 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%).

Discussion: 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.


Figure: Change in Bowel Urgency Measures from Baseline at Week 12 and Week 28, BOCF

Disclosures:
Silvio Danese: AbbVie – Consultant, Lecture fees. Alimentiv – Consultant. Allergan – Consultant. Amgen – Consultant, Lecture fees. AstraZeneca – Consultant. Athos Therapeutics – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Celgene – Consultant. Celltrion – Consultant. Eli Lilly – Consultant. Enthera – Consultant. F. Hoffmann-La Roche Ltd – Consultant. Ferring Pharmaceuticals Inc. – Consultant, Lecture fees. Gilead – Consultant, Lecture fees. Hospira – Consultant. Inotrem – Consultant. Johnson & Johnson – Consultant, Lecture fees. MSD – Consultant. Mundipharma – Consultant. Mylan – Consultant, Lecture fees. Pfizer – Consultant, Lecture fees. Sandoz – Consultant. Sublimity Therapeutics – Consultant. Takeda – Consultant, Lecture fees. TiGenix – Consultant. UCB Inc. – Consultant. Vifor (International) Ltd. – Consultant.
Axel Dignass: Abbvie – Consultant, fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and endpoint committees; manuscripts, Speakers Bureau. Abivax – fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees. Amgen – Consultant. Arena Pharmaceuticals – Consultant. Biogen – Consultant, Speakers Bureau. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant. CED Service GmbH – Speakers Bureau. Celltrion – Consultant, Speakers Bureau. Dr Falk Foundation – Consultant, fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and endpoint committees; manuscripts, Speakers Bureau. Ferring – Consultant, Speakers Bureau. Fresenius Kabi – Consultant. Galapagos – Consultant, fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees, Speakers Bureau. Gilead – fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees, Speakers Bureau. High5MD – Speakers Bureau. Johnson & Johnson – Consultant, fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and endpoint committees; manuscripts, Speakers Bureau. Lilly – Consultant. Materia – Speakers Bureau. MedToday – Speakers Bureau. MSD – Consultant, Speakers Bureau. Pfizer – Consultant, fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees, Speakers Bureau. Pharmacosmos – Consultant. Prima – Speakers Bureau. Roche – Consultant. Sandoz – Consultant. Stada – Consultant. Takeda – Consultant, manuscript preparation, Speakers Bureau. Thieme – manuscript preparation. Tilliots – Consultant, Speakers Bureau. UniMed Verlag – manuscript preparation. Vifor Pharma – Consultant, Speakers Bureau.
David Laharie: AbbVie – Advisory Committee/Board Member, Consultant, Transport, Fees.. Alfasigma – Advisory Committee/Board Member, Consultant, Transport or Fees. Amgen – Advisory Committee/Board Member, Consultant, Transport, Fees.. Celltrion – Advisory Committee/Board Member, Consultant, Transport, Fees.. Eli Lilly and Company – Advisory Committee/Board Member, Consultant, Transport, Fees.. Ferring Pharmaceuticals – Advisory Committee/Board Member, Consultant, Transport, Fees.. Janssen – Advisory Committee/Board Member, Consultant, Transport, Fees.. Medac – Advisory Committee/Board Member, Consultant, Transport or Fees. Merck Sharp & Dohme – Advisory Committee/Board Member, Consultant, Transport, Fees.. Pfizer – Advisory Committee/Board Member, Consultant, Transport, Fees.. Prometheus – Advisory Committee/Board Member, Consultant, Transport, Fees.. Takeda – Advisory Committee/Board Member, Consultant, Transport, Fees.. Theradiag – Advisory Committee/Board Member, Consultant, Transport, Fees..
Jimmy Limdi: AbbVie – Consultant, Grant/Research Support, Speakers Bureau. Abivax – Consultant, Speakers Bureau. AlfaSigma – Consultant, Speakers Bureau. Biohit – Consultant, Speakers Bureau. Bristol Myers Squibb – Consultant, Speakers Bureau. Celltrion – Consultant, Speakers Bureau. Eli Lilly and Company – Consultant, Speakers Bureau. Ferring – Consultant, Speakers Bureau. Galapagos – Consultant, Grant/Research Support, Speakers Bureau. Johnson & Johnson – Advisor or Review Panel Member, Speakers Bureau. MSD – Consultant, Speakers Bureau. Pfizer – Consultant, Speakers Bureau. Takeda – Consultant, Grant/Research Support, Speakers Bureau.
Radoslaw Kempinski: AbbVie – Lecture fees. Aboca S.p.A. Società Agricola – Lecture fees. Eli Lilly and Company – Lecture fees. Ferring – Lecture fees. Takeda – Grant/Research Support.
James D. Lewis: AbbVie – Grant/Research Support. Amgen – Advisory Committee/Board Member, Consultant, Data monitoring committee. Crohn’s & Colitis Foundation – Advisory Committee/Board Member, Consultant, Data monitoring committee. Dark Canyon Labs – Stock Options. Eli Lilly and Company – Advisory Committee/Board Member, Consultant, Grant/Research Support, Data monitoring committee. Galapagos – Advisory Committee/Board Member, Consultant, Data monitoring committee. Janssen Pharmaceuticals (Johnson & Johnson) – Advisory Committee/Board Member, Consultant, Grant/Research Support, Data monitoring committee, Educational grant. Merck – Advisory Committee/Board Member, Consultant, Data monitoring committee. Nestle Health Science – Grant/Research Support. Odyssey Therapeutics – Advisory Committee/Board Member, Consultant, Data monitoring committee. Pfizer – Advisory Committee/Board Member, Consultant, Data monitoring committee. Protagonist Therapeutics – Advisory Committee/Board Member, Consultant, Data monitoring committee. Sanofi – Advisory Committee/Board Member, Consultant, Data monitoring committee. Spyre Pharmaceuticals – Advisory Committee/Board Member, Consultant, Data monitoring committee. Takeda – Grant/Research Support.
Ziad Younes: AbbVie – Grant/Research Support, Speakers Bureau. Axcella – Grant/Research Support. Bristol Myers Squibb – Grant/Research Support, Speakers Bureau. CymaBay – Grant/Research Support. Galectin – Grant/Research Support. Intercept – Consultant, Grant/Research Support, Speakers Bureau. Inventiva – Grant/Research Support. Madrigal – Consultant, Grant/Research Support. NGM – Grant/Research Support. Novo Nordisk – Grant/Research Support. NST – Grant/Research Support. Poxel – Grant/Research Support. Sagimet – Grant/Research Support.
Erica Cohen: AbbVie – Speakers Bureau. Eli Lilly and Company – Speakers Bureau. Janssen – Speakers Bureau. Pfizer – Advisory Committee/Board Member, Consultant. PRIME Education – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau.
Karla Alaka: Eli Lilly and Company – Employee, Stock Options.
William Eastman: Eli Lilly and Company – Employee, Stock Options.
Tian Tian: Eli Lilly and Company – Employee, Stock Options.
Isabel Redondo: Eli Lilly and Company – Employee, Stock Options.
David Rubin: AbbVie – Advisory Committee/Board Member, Consultant, Speaker fees. Abivax SA – Consultant. Altrubio – Advisory Committee/Board Member, Consultant, Speaker feees, Stock Options. Avalo – Advisory Committee/Board Member, Consultant, Speaker fees. Bausch Health – Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant, Speaker fees. Buhlmann Diagnostics – Advisory Committee/Board Member, Consultant, Speaker fees. Celltrion – Consultant. ClostraBio – Consultant. Connect BioPharma – Consultant. Cornerstones Health, Inc – Board of Directors membership. Douglas Pharmaceuticals – Consultant. Eli Lilly & Co. – Consultant. Foresee, Genentech (Roche) Inc. – Consultant. Image Analysis Group – Consultant. InDex Pharmaceutical – Consultant. Intouch Group – Advisory Committee/Board Member, Consultant, Speaker fees. Iterative Health – Advisory Committee/Board Member, Consultant, Speaker fees. Iterative Health – Stock Options. Janssen Pharmaceuticals – Consultant. Lilly – Advisory Committee/Board Member, Consultant, Speaker fees. Odyssey Therapeutics – Consultant. Pfizer – Advisory Committee/Board Member, Consultant, Speaker fees. Sanofi – Consultant. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speaker fees. Throne – Consultant. Vedanta – Consultant.
Marla Dubinsky: AbbVie – Consultant, Grant/Research Support. Arena – Consultant. Astra Zeneca – Consultant. Boehringer Ingelheim – Consultant. Celgene – Consultant. Eli Lilly – Consultant. Gilead – Consultant. Janssen – Consultant, Grant/Research Support. Merck – Consultant. Pfizer – Consultant. Prometheus Laboratories – Consultant, Grant/Research Support. Sanofi – Consultant. Spyre – Consultant. Takeda – Consultant. Trellus Health – Stock Options, Stock-publicly held company(excluding mutual/index funds). UCB – Consultant.

Silvio Danese, MD, PhD¹, Axel Dignass, MD, PhD², David Laharie, ³, Jimmy Limdi, MD⁴, Radoslaw Kempinski, MD, PhD⁵, James D. Lewis, MD⁶, Ziad Younes, MD⁷, Erica R. Cohen, MD⁸, Karla Alaka, ⁹, William J. Eastman, ⁹, Tian Tian, ⁹, Isabel Redondo, MD⁹, David T. Rubin, MD¹⁰, Marla C. Dubinsky, MD¹¹. P3231 - 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, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.