B0366 - Effect of Mirikizumab on Bowel Urgency Clinically Meaningful Improvement and Remission: Results From the Phase 3 LUCENT Induction and Maintenance Studies

Monday, October 24, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

David T. Rubin, MD, FACG

University of Chicago Medicine Inflammatory Bowel Disease Center
Chicago, IL

Simon Travis, DPhil¹, Toshifumi Hibi, MD, PhD², Tadakazu Hisamatsu, MD, PhD³, Deborah Fisher, MD, MHS⁴, Mingyang Shan, PhD⁴, Theresa Hunter Gibble, PhD⁴, David T. Rubin, MD, FACG⁵
¹Kennedy Institute, University of Oxford, Oxford, England, United Kingdom; ²Center for Advanced IBD Research and Treatment Kitasato, University Kitasato Institute Hospital, Minato-ku, Tokyo, Japan; ³Kyorin University School of Medicine, Tokyo, Tokyo, Japan; ⁴Eli Lilly and Company, Indianapolis, IN; ⁵University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL

Introduction: Bowel urgency (BU) was assessed in mirikizumab (miri) Phase 3 LUCENT studies in moderately-to-severely active ulcerative colitis (UC) using the validated Urgency Numeric Rating Scale (UNRS). UNRS measures BU severity in the past 24 hours from 0 (no urgency) to 10 (worst possible urgency). Psychometric evaluation of the UNRS showed Clinically Meaningful Improvement (CMI) is >3 point change; Remission is a score of 0 or 1. This analysis evaluated the proportions of patients in LUCENT studies achieving BU CMI and BU remission.

Methods: The modified intent-to-treat (mITT) population (patients receiving ≥1 dose of miri or placebo (PBO); N= 1281) was randomized at induction study baseline in a 3:1 ratio to IV doses of 300mg miri or PBO every 4 weeks (Q4W) during induction (W0, 4, and 8). Patients achieving Clinical Response, measured by Modified Mayo Score (MMS), to miri during induction were re-randomized at W0 of the maintenance study in a 2:1 ratio to subcutaneous (SC) 200mg miri or PBO Q4W through W40 (52 weeks of treatment). Patients recorded their UNRS score daily in an e-diary. Mean weekly UNRS scores were calculated from diary data if ≥4 days of data were available. Rates of BU CMI and BU remission in the miri v PBO groups were compared at W12 (induction) in the mITT population with a baseline UNRS score ≥3, and W52 (maintenance) among miri clinical responders at W12 with a baseline UNRS score ≥3. Cochran-Mantel-Haenszel tests with non-responder imputation for missing values were used for all treatment comparisons.

Results: Patient population: mean age 43 years, 60% male, disease duration 7 years; 63.0% left-sided colitis; 36.3% pancolitis; 46.7% moderate disease (MMS 4-6); 53.2% severe disease (MMS 7-9). Significantly higher proportions of miri versus PBO patients achieved BU CMI (48.7% v 32.2%) and BU remission (22.1% v 12.3%) at W12 (both p< 0.001; Table) in the induction study. Similarly, at W40 of maintenance, significantly greater proportion of miri patients achieved BU CMI (65.2% v 41.9%) and BU remission (42.9% v 25.0%) compared to PBO among miri induction responders (both p< 0.001; Table).

Discussion: Miri had a highly significant and clinically meaningful benefit on reducing bowel urgency, one of the most disruptive UC symptoms. The Urgency Numeric Rating Scale usefully quantified the baseline level and change in bowel urgency after treatment across a spectrum of severity.

	Induction (W12 Analysis)			Maintenance (W40 Analysis)
	300mg miri IV N= 868	PBO IV N= 294	p-value	200mg miri SC N= 365	PBO SC N= 179	p-value
Baseline bowel urgency W0 UNRS Score (Mean ± SD)	6.1 ± 2.2	6.2 ± 2.2	─	6.0 ± 2.2	6.2 ± 1.9	─
UNRS change from baseline (LSM ± SE)	-2.6 ± 0.083^a	-1.63 ± 0.141^a	p< 0.00001^a	-3.8 ± 0.139^h	-2.7± 0.202^h	p< 0.001^{b, h}
Bowel urgency clinically meaningful improvement (N [%])^c	395 [48.7%]^e	89 [32.2%]^e	p< 0.001^g	219 [65.2%]^f	72 [41.9%]^f	p< 0.001^g
Bowel Urgency Remission^d (N [%])	179 [22.1%]^e	34 [12.3%]^e	P< 0.001^g	144 [42.9%]^{f, h}	43 [25.0%]^{f, h}	P< 0.001^g,h
Abbreviations: IV = intravenous; LSM = least squares mean; PBO = placebo; SC = subcutaneous; SD = standard deviation’ UNRS = Urgency Numeric Rating Scale. ^aResults previously disclosed at ECCO 2022; D’Haens et al. J Crohn’s Colitis. 2022;16(Supplement 1): i028-i029. ^bTreatment comparison is from a mixed model for repeated measures model that contains treatment, baseline value, visit, interaction of baseline value by visit, interaction of treatment by visit, and stratification factors. ^cBowel urgency clinically meaningful improvement is defined as a reduction in the UNRS of ≥3 points. ^dBowel urgency remission is an UNRS score of ‘0’ or ‘1’. ^eComparisons between miri and PBO at W12 are shown for patients with a baseline UNRS score ≥3; N=811 for 300mg miri and N= 276 for PBO. ^fComparisons between miri and PBO at W40 are shown for miri induction responders with a UNRS score ≥3 at baseline; N= 336 for 200mg miri and N=172 for PBO. ^gCochran-Mantel-Haenszel tests with non-responder imputation were used for treatment comparisons. ^hResults previously disclosed at DDW 2022.

Table: Table: Assessment Bowel Urgency Clinically Meaningful Improvement and Remission in Patients Treated with Mirikizumab v Placebo at Weeks 12 and 40

Disclosures:

Simon Travis: Abacus – Consultant. Abbvie – Consultant, Grant/Research Support. Actial – Consultant. ai4gi – Consultant. Alcimed – Consultant. Allergan – Consultant. Amgen – Consultant. Apexian – Consultant. Aptel – Consultant. Arena – Consultant. Asahi – Consultant. Aspen – Consultant. Astellas – Consultant. AstraZeneca – Consultant. Atlantic – Consultant. Barco – Consultant. Biocare – Consultant. Biogen – Consultant. BLPharma – Consultant. BMS – Consultant. Boehringer Ingelheim – Consultant. Buhlmann – Consultant, Grant/Research Support. Calcico – Consultant. Celgene – Consultant, Grant/Research Support. Cellerix – Consultant. Cerimon – Consultant. ChemoCentryx – Consultant. Chiesi – Consultant. Cisbio – Consultant. ComCast – Consultant. Coronado – Consultant. Cosmo – Consultant. Ducentis – Consultant. Dynavax – Consultant. ECCO – Grant/Research Support. Elan – Consultant. Enterome – Consultant. EQrX – Consultant. Equillium – Consultant. Falk – Consultant. Ferring – Consultant. FPRT Bio – Consultant. Galapagos – Consultant. Genentech/Roche – Consultant. Genzyme – Consultant. Gilead – Consultant. Glenmark – Consultant. Grunenthal – Consultant. GSK – Consultant. GW Pharmaceuticals – Consultant. Helmsley Trust – Grant/Research Support. Immunocore – Consultant. Immunometabolism – Consultant. Indigo – Consultant. IOIBD – Grant/Research Support. Janssen – Consultant, Grant/Research Support. Lexicon – Consultant. Lilly – Consultant, Grant/Research Support. Medarex – Consultant. Medtrix – Consultant. Merck – Consultant. Merrimack – Consultant. Mestag – Consultant. Millenium – Consultant. Neovacs – Consultant. Norman Collisson Foundation – Grant/Research Support. Novartis – Consultant. Novo Nordisk – Consultant. NPS-Nycomed – Consultant. Ocera – Consultant. Optima – Consultant. Origin – Consultant. Otsuka – Consultant. P&G – Consultant. Palau – Consultant. Pentax – Consultant. Pfizer – Consultant, Grant/Research Support. Pharmaventure – Consultant. Phesi – Consultant. Phillips – Consultant. Pronota – Consultant. Protagonist – Consultant. Proximagen – Consultant. Resolute – Consultant. Robarts – Consultant. Sandoz – Consultant. Santarus – Consultant. Satisfai – Consultant. Sensyne Health – Consultant. Shire – Consultant. SigmoidPharma – Consultant. Sorriso – Consultant. Souffinez – Consultant. Syndermix – Consultant. Synthon – Consultant. Takeda – Consultant, Grant/Research Support. Theravance – Consultant. Tigenix – Consultant. Tillotts – Consultant. Topivert – Consultant. Trino Therapeutics with Wellcome Trust – Consultant. TxCell – Consultant. UCB Pharma – Consultant, Grant/Research Support. UKIERI – Grant/Research Support. Vertex – Consultant. VHsquared – Consultant. Vifor – Consultant, Grant/Research Support. Warner Chilcott and Zeria – Consultant.

Toshifumi Hibi: Abbvie GK – Consultant, Grant/Research Support. Activaid – Grant/Research Support. Alfresa Pharma Corporation – Grant/Research Support. Apo Puls Station – Consultant. Bristol-Myaers Squibb – Consultant, Grant/Research Support. Celltrion – Consultant. EA Pharma – Consultant. Eli Lilly and Company – Consultant, Grant/Research Support. Ferring Pharmaceuticals – Grant/Research Support. Gilead Sciences – Consultant, Grant/Research Support. Janssen – Consultant, Grant/Research Support. JMDC Inc – Grant/Research Support. Kyorin – Consultant. Mitsubishi-TanabePharma – Consultant. Mochida Pharmaceutical Co – Grant/Research Support. Nichi-IkoPharmaceutical – Consultant. Nippon Kayaku Co. – Grant/Research Support. Pfizer – Consultant, Grant/Research Support. Takeda Pharmaceutical – Consultant, Grant/Research Support. Zeria Pharmaceutical – Consultant.

Tadakazu Hisamatsu: AbbVie – Consultant, Grant/Research Support, Lecture fees. Celgene – Consultant. Daiichi-Sankyo – Grant/Research Support. EA Pharma Co, Ltd – Consultant, Grant/Research Support, Lecture fees. Janssen Research & Development, LLC – Consultant, lecture fees. JIMRO – Grant/Research Support. JIMRO Co – Consultant, Grant/Research Support. Kyorin Pharmaceutical Co. Ltd – Consultant, Grant/Research Support. Mitsubishi Tanabe Pharma Corporation – Grant/Research Support, Lecture fees. Mochida Pharmaceutical Co., Ltd – Grant/Research Support, lecture fees. Nichi-Iko Pharmaceutical Co., Ltd – Consultant. Nippon Kayaku Co., Ltd – Grant/Research Support. Pfizer Inc – Consultant, Grant/Research Support, lecture fees. Takeda Pharmaceutical Co., Ltd – Grant/Research Support, Lecture fees. Zeria Pharmaceutical Co. Ltd – Grant/Research Support.

Deborah Fisher: Eli Lilly and Company – Employee, Stock-publicly held company(excluding mutual/index funds).

Mingyang Shan: Eli Lilly and Company – Employee, Stock-publicly held company(excluding mutual/index funds).

Theresa Hunter Gibble: Eli Lilly and Company – Employee.

David Rubin: AbbVie – Consultant. Alimentiv Inc. – Consultant. AltruBio – Consultant. Arena Pharmaceuticals – Consultant. Aslan Pharmaceuticals – Consultant. Athos Therapeutics – Consultant. Bellatrix Pharmaceuticals – Consultant. Boehringer Ingelheim, Ltd. – Consultant. Bristol Myers Squibb – Consultant. Celgene Corp/Syneos – Consultant. ClostraBio – Consultant. Connect BioPharma – Consultant. EcoR1 – Consultant. Genentech/Roche – Consultant. Gilead Sciences – Consultant. Ironwood Pharmaceuticals – Consultant. Iterative Scopes – Consultant. Janssen – Consultant. Kaleido Biosciences – Consultant. Lilly, Eli & Co – Consultant. Materia Prima – Consultant. Pfizer – Consultant. Prometheus Biosciences – Consultant. Reistone Biopharma – Consultant. Seres Therapeutics, Inc – Consultant. Takeda – Consultant, Grant/Research Support. Target RWE – Consultant. Techlab – Consultant. Trellus Health – Consultant.

Simon Travis, DPhil¹, Toshifumi Hibi, MD, PhD², Tadakazu Hisamatsu, MD, PhD³, Deborah Fisher, MD, MHS⁴, Mingyang Shan, PhD⁴, Theresa Hunter Gibble, PhD⁴, David T. Rubin, MD, FACG⁵. B0366 - Effect of Mirikizumab on Bowel Urgency Clinically Meaningful Improvement and Remission: Results From the Phase 3 LUCENT Induction and Maintenance Studies, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.