A0393 - Mirikizumab Improves Quality of Life in Moderately-to-Severely Active UC: Improvement in IBDQ Scores in Participants of LUCENT-1 and LUCENT-2 Randomized, Double-Blind, Placebo-Controlled Phase 3 Trials

Sunday, October 23, 2022

5:00 PM – 7:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

Bruce E. Sands, MD, MS, FACG

Icahn School of Medicine at Mount Sinai
New York, NY

Bruce E. Sands, MD, MS, FACG¹, Brian Feagan, ², Theresa Hunter Gibble, PhD³, Kristina A. Traxler, PharmD³, Nathan Morris, PhD³, Xingyuan Li, PhD³, Stefan Schreiber, MD⁴, Vipul Jairath, MBChB, DPhil⁵, Alessandro Armuzzi, MD, PhD⁶
¹Icahn School of Medicine at Mount Sinai, New York, NY; ²Alimentiv Inc., London, ON, Canada; ³Eli Lilly and Company, Indianapolis, IN; ⁴University Hospital Schleswig-Holstein, Kiel University, Kiel, Schleswig-Holstein, Germany; ⁵Western University, London, ON, Canada; ⁶Humanitas Research Hospital, Rozzano, Lombardia, Italy

Introduction: The Inflammatory Bowel Disease Questionnaire (IBDQ) is a measure of health‑related quality of life (QoL). This analysis evaluated effect of mirikizumab (miri) vs placebo (PBO) on IBDQ scores in patients (pts) with moderately-to-severely active ulcerative colitis (UC) who had failed prior conventional or biologic therapy in a Phase 3, double-blind, 12-week (W) induction study (LUCENT-1) followed by a 40W maintenance study (LUCENT-2) for a total of 52W continuous therapy.

Methods: Pts (N=1162) in LUCENT-1 were randomized 3:1 to receive 300mg miri or PBO intravenously once every four weeks (Q4W). 544 pts who achieved Modified Mayo Score Clinical Response to miri by W12 of induction were rerandomized 2:1 in LUCENT-2 to subcutaneous miri 200mg or PBO Q4W in maintenance period. Randomization was stratified by previous biologic therapy failure, baseline corticosteroid use, and region. LUCENT-1 stratification included baseline (BL) disease activity, and LUCENT-2 included LUCENT-1 clinical remission status. The least squares mean change from BL in IBDQ scores at W12 of induction and W40 of maintenance was determined using analysis of covariance models. BL was W0 of therapy and stratification factors and BL scores were used as covariates. The Minimal Clinically Important Difference (MCID) was defined as an improvement of ≥16 points in total IBDQ score (IBDQ response) and IBDQ remission as a total score ≥170 points. IBDQ response and remission were calculated using non-responder imputations. Treatments were compared using the common risk difference (risk diff).

Results: Miri treatment resulted in significantly greater improvement from BL in IBDQ total and domain scores vs PBO at both W12 of induction and W40 of maintenance (52W treatment) (Table). The proportions of pts who achieved an IBDQ response was significantly greater for miri treated pts vs PBO at W12 (risk diff =17.1[95%CI:10.7, 23.5]) and W40 (29.5 [21.0, 37.9]). Significantly greater proportions of pts receiving miri achieved IBDQ remission at W12 (18.1 [11.8, 24.4]) and W40 (28.5 [20.1, 37.0]) vs PBO (all evaluations and timepoints: p< 0.001).

Discussion: Pts reported significantly greater improvements in IBDQ scores at induction and maintenance with miri compared to PBO. Over 75% of pts achieved a clinically meaningful improvement in QoL, as measured by IBDQ response, at the end of the 52 weeks of miri treatment.

	IBDQ Total Score¹		IBDQ Response²Score Improvement ≥16		IBDQ Remission²IBDQ Total Score ≥170
	LSM Change from BL (SE)	LSM Diff (SE)	n (%)	Risk Diff (95% CI)	n (%)	Risk Diff (95% CI)
LUCENT-1 Week 12 of Induction
PBO IV Q4W (N=294)	25.21 (1.80)		164 (55.8)		117 (39.8)
Miri 300 mg IV Q4W (N=868)	38.42 (1.11)	13.21 (2.01)*	631 (72.7)	17.1 (10.7, 23.5)*	499 (57.5)	18.1 (11.8, 24.4)*
LUCENT-2 Week 40 of Maintenance (52 Weeks of Continuous Therapy) of Miri Induction Responders
PBO SC (N=179)	24.51 (2.77)		88 (49.2)		77 (43.0)
Miri 200 mg SC (N=365)	49.75 (2.10)	25.24 (3.09)*	289 (79.2)	29.5 (21.0, 37.9)*	264 (72.3)	28.5 (20.1, 37.0)*
Abbreviations: BL=baseline; CI=confidence interval; Diff=difference; IBDQ=Inflammatory Bowel Disease Questionnaire; IV=intravenous; LSM=least squares mean; Miri=mirikizumab; n=number of patients in the specified category; N=number of patients in the analysis population; PBO=placebo; Q4W=every 4 weeks; Risk Diff=common risk difference; SC=subcutaneous; SE=standard error ¹Inflammatory Bowel Disease Questionnaire domains and total scores were evaluated by analysis of covariance with modified baseline observation carried forward and adjustment for covariates. ²Inflammatory Bowel Disease Questionnaire-based measurements for clinical response and remission were analyzed using non-responder imputation. The common risk difference was the stratification-adjusted difference in the proportion of participants receiving mirikizumab minus the proportion of participants receiving placebo. *p< 0.001

Table: LUCENT-1 and LUCENT-2 Trials Change from Baseline in the Inflammatory Bowel Disease Questionnaire

Disclosures:

Bruce Sands: Abivax – Consultant, Speaking. Amgen – Consultant. Arena Pharmaceuticals – Consultant. Artugen Therapeutics – Consultant. AstraZeneca – Consultant. Bacainn Therapeutics – Consultant. Boehringer-Ingelheim – Consultant. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant, speaking, research funding. Calibr – Consultant. Celltrion Healthcare – Consultant. ClostraBio – Consultant. Eli Lilly and Company – Consultant. Entera – Consultant. Evommune – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. Gossamer Bio – Consultant. InDex Pharmaceuticals – Consultant. Innovation Therapeutics – Consultant. Inotrem – Consultant. Ironwood Pharmaceuticals – Consultant. Janssen – Consultant, Grant/Research Support, speaking. Kaleido – Consultant. Kallyope – Consultant. Miro Bio – Consultant. Morphic Therapeutics – Consultant. MRM Health – Consultant. Pfizer – Consultant, speaking. Progenity – Consultant. Prometheus Biosciences – Consultant. Protagonist Therapeutics – Consultant. Q32 Bio – Consultant. Surrozen – Consultant. Takeda – Consultant, Speaking. Teva – Consultant. TLL Pharmaceutical – Consultant. USWM Enterprises – Consultant. VielaBio – Consultant.

Brian Feagan: AbbVie – Advisor or Review Panel Member, Grant/Research Support, Speakers Bureau. Akebia Therapeutics – Advisor or Review Panel Member. Allergan – Advisor or Review Panel Member. Amgen – Advisor or Review Panel Member, Grant/Research Support. Applied Molecular Transport – Advisor or Review Panel Member. Aptevo Therapeutics – Advisor or Review Panel Member. AstraZeneca – Advisor or Review Panel Member, Grant/Research Support. Atlantic Pharmaceuticals – Advisor or Review Panel Member, Grant/Research Support. Avir Pharma – Advisor or Review Panel Member. Biogen Idec – Advisor or Review Panel Member. BioMx Israel – Advisor or Review Panel Member. Boehringer Ingelheim – Advisor or Review Panel Member, Grant/Research Support. Bristol-Myers Squibb – Advisor or Review Panel Member. Calypso Biotech – Advisor or Review Panel Member. Celgene – Advisor or Review Panel Member, Grant/Research Support. Celltech – Grant/Research Support. Elan/Biogen – Advisor or Review Panel Member. Eli Lilly and Company – Advisor or Review Panel Member, Speakers Bureau. EnGene – Advisor or Review Panel Member. Ferring Pharma – Advisor or Review Panel Member. Galapagos – Advisor or Review Panel Member. Genentech/Hoffmann-La Roche – Grant/Research Support. GiCare Pharma – Advisor or Review Panel Member. Gilead – Advisor or Review Panel Member, Grant/Research Support. Glaxo Smith Kline – Advisor or Review Panel Member, Grant/Research Support. Gossamer Pharma – Advisor or Review Panel Member. Inception IBD – Advisor or Review Panel Member. Intact Therapeutics – Advisor or Review Panel Member. Janssen – Advisor or Review Panel Member, Grant/Research Support, Speakers Bureau. Kyowa Kakko Kirin – Advisor or Review Panel Member. Lexicon – Advisor or Review Panel Member. Lycera BioTech – Advisor or Review Panel Member. Merck – Advisor or Review Panel Member. Mesoblast Pharma – Advisor or Review Panel Member. Millennium – Advisor or Review Panel Member. Nestles – Advisor or Review Panel Member. Nextbiotix – Advisor or Review Panel Member. Novo Nordisk – Advisor or Review Panel Member. ParImmune – Advisor or Review Panel Member. Parvus Therapeutics – Advisor or Review Panel Member. Pfizer – Advisor or Review Panel Member, Grant/Research Support. Progenity – Advisor or Review Panel Member. Prometheus Therapeutics and Diagnostics – Advisor or Review Panel Member. Protagonist – Advisor or Review Panel Member. Qu Biologics – Advisor or Review Panel Member. Receptos – Advisor or Review Panel Member. Robarts Clinical Trials – Advisory Committee/Board Member. Roche – Advisor or Review Panel Member, Grant/Research Support. Salix Pharma – Advisor or Review Panel Member. Sanofi – Grant/Research Support. Santarus – Grant/Research Support. Shire – Advisor or Review Panel Member. Sienna Biologics – Advisor or Review Panel Member. Sigmoid Pharma – Advisor or Review Panel Member. Sterna Biologicals – Advisor or Review Panel Member. Synergy Pharma – Advisor or Review Panel Member. Takeda – Advisor or Review Panel Member, Grant/Research Support, Speakers Bureau. Teva Pharma – Advisor or Review Panel Member. TiGenix – Advisor or Review Panel Member. Tillotts – Advisor or Review Panel Member, Speakers Bureau. Tillotts Pharma – Grant/Research Support. UCB – Advisor or Review Panel Member, Grant/Research Support, Speakers Bureau. Vertex Pharma – Advisor or Review Panel Member. VHsquared – Advisor or Review Panel Member. Vivelix Pharmaceuticals – Advisor or Review Panel Member. Zyngenia – Advisor or Review Panel Member.

Theresa Hunter Gibble: Eli Lilly and Company – Employee.

Kristina Traxler: Eli Lilly and Company – Employee.

Nathan Morris: Eli Lilly and Company – Employee.

Xingyuan Li: Eli Lilly and Company – Employee.

Stefan Schreiber: AbbVie – Consultant, Personal fees. Arena – Consultant, Personal fees. Biogen – Consultant, Personal fees. Bristol-Myers Squibb – Consultant, Personal fees. Celgene – Consultant, Personal fees. Celltrion – Consultant, Personal fees. Eli Lilly and Company – Consultant, Personal fees. Falk – Consultant, Personal fees. Ferring – Consultant, Personal fees. Fresenius – Consultant, Personal fees. Galapagos/Gilead Sciences – Consultant, Personal fees. IMAB – Consultant, Personal fees. Janssen – Consultant, Personal fees. MSD – Consultant, Personal fees. Mylan – Consultant, Personal fees. Pfizer Inc – Consultant, Personal fees. Protagonist – Consultant, Personal fees. Provention Bio – Consultant, Personal fees. Takeda – Consultant, Personal fees. Theravance – Consultant, Personal fees.

Vipul Jairath: AbbVie – consulting/advisory board fees, speaker’s fees. Alimentiv Inc – Consulting/advisory board fees. Arena pharmaceuticals – consulting/advisory board fees. Asahi Kasei Pharma – Consulting/advisory board fees. Asieris – consulting/advisory board fees. AstraZeneca – consulting/advisory board fees. Bristol Myers Squibb – consulting/advisory board fees, speaker’s fees. Celltrion – consulting/advisory board fees. Eli Lilly and Company – consulting/advisory board fees. Ferring – consulting/advisory board fees, speaker's fees. Flagship Pioneering – consulting/advisory board fees. Fresenius Kabi – consulting/advisory board fees, speaker’s fees. Galapagos – consulting/advisory board fees, speaker’s fees. Genentech – consulting/advisory board fees. Gilead – consulting/advisory board fees. GlaxoSmithKline – consulting/advisory board fees. Janssen – consulting/advisory board fees, speaker’s fees. Merck – consulting/advisory board fees. Metacrine – consulting/advisory board fees. Mylan – consulting/advisory board fees. Pandion – consulting/advisory board fees. Pendopharm – consulting/advisory board fees. Pfizer – consulting/advisory board fees, speaker’s fees. Prometheus – consulting/advisory board fees. Protagonist Therapeutics – consulting/advisory board fees. Reistone Biopharma – consulting/advisory board fees. Roche – consulting/advisory board fees. Sandoz – consulting/advisory board fees. Second Genome – consulting/advisory board fees. Shire – speaker’s fees. Sorriso pharmaceuticals – consulting/advisory board fees. Takeda – consulting/advisory board fees, speaker’s fees. Teva – consulting/advisory board fees. Topivert – consulting/advisory board fees. Ventyx Biosciences – consulting/advisory board fees. Vividion Therapeutics – consulting/advisory board fees.

Alessandro Armuzzi: AbbVie – consulting/advisory board fees, speaker’s fees. Allergan – consulting/advisory board fees. Amgen – consulting/advisory board fees, speaker’s fees. Arena – consulting/advisory board fees, speaker’s fees. Biogen – Grant/Research Support, consulting/advisory board fees, speaker’s fees. Boehringer Ingelheim – consulting/advisory board fees. Bristol-Myers Squibb – consulting/advisory board fees, speaker’s fees. Celgene – consulting/advisory board fees. Celltrion – consulting/advisory board fees. Eli Lilly and Company – consulting/advisory board fees, speaker’s fees. Ferring – consulting/advisory board fees, speaker’s fees. Galapagos – consulting/advisory board fees, speaker’s fees. Gilead – consulting/advisory board fees, speaker’s fees. Janssen – consulting/advisory board fees, speaker’s fees. MSD – Grant/Research Support, consulting/advisory board fees, speaker’s fees. Mylan – consulting/advisory board fees. Novartis – Speaker’s fees. Pfizer – Grant/Research Support, consulting/advisory board fees, speaker’s fees. Protagonist Therapeutics – consulting/advisory board fees. Roche – consulting/advisory board fees, speaker’s fees. Samsung Bioepis – consulting/advisory board fees, speaker’s fees. Sandoz – consulting/advisory board fees, speaker’s fees. Takeda – Grant/Research Support, consulting/advisory board fees, speaker’s fees. Tigenix – Speaker’s fees.

Bruce E. Sands, MD, MS, FACG¹, Brian Feagan, ², Theresa Hunter Gibble, PhD³, Kristina A. Traxler, PharmD³, Nathan Morris, PhD³, Xingyuan Li, PhD³, Stefan Schreiber, MD⁴, Vipul Jairath, MBChB, DPhil⁵, Alessandro Armuzzi, MD, PhD⁶. A0393 - Mirikizumab Improves Quality of Life in Moderately-to-Severely Active UC: Improvement in IBDQ Scores in Participants of LUCENT-1 and LUCENT-2 Randomized, Double-Blind, Placebo-Controlled Phase 3 Trials, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.