B0350 - Mirikizumab Improves Work Productivity and Activity Impairment Questionnaire Scores in Moderately-to-Severely Active UC: The LUCENT-1 and LUCENT-2 Randomized, Double-Blind, Placebo-Controlled Phase 3 Studies

Monday, October 24, 2022

10:00 AM – 12:00 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: This analysis compares mirikizumab (miri) to placebo (PBO) for improvement in the Work Productivity and Activity Impairment Questionnaire Ulcerative Colitis (WPAI:UC) in participants of LUCENT-1 and LUCENT-2, phase 3 clinical trials who had moderately-to-severely active UC and had failed prior conventional or biologic therapies.

Methods: 1162 patients (pts) in LUCENT‑1 12‑week induction study were randomized 3:1 to receive 300mg miri or PBO intravenously once every 4 weeks (Q4W). 544 pts who completed induction and achieved Modified Mayo Score (MMS) Clinical Response with miri were rerandomized 2:1 in LUCENT‑2 to a 40W maintenance treatment of miri 200mg or PBO subcutaneously Q4W for a total of 52W treatment. Randomization was stratified by previous biologic therapy failure, baseline (BL) corticosteroid use, and region. Stratification for LUCENT‑1 included BL disease activity, and LUCENT‑2 included LUCENT‑1 clinical remission status. WPAI:UC scores between 0%-100% were calculated from pts‑reported measurements, with a higher score indicating greater impairment. Evaluations of the WPAI:UC domain of overall activity impairment included all respondents, while domains of absenteeism, presenteeism, and work productivity loss required employment at the time of the analyses. Changes from W0 BL at W12 (induction) and W40 (maintenance; 52W treatment) were evaluated by analysis of covariance. Stratification factors and BL scores were used as covariates. Results were reported as least squares mean differences (LSM diff) of miri vs PBO.

Results: At BL, 60.67% (N=705) of pts reported employment. At W12 of induction, activity impairment, absenteeism, presenteeism, and work productivity loss were significantly reduced from BL in miri treated pts vs PBO (Table). Of the pts who achieved W12 MMS Clinical Response, those who continued receiving miri had sustained improvements in the WPAI:UC change from BL at W40 of maintenance vs those who received PBO, including activity impairment, presenteeism, and work productivity loss. Absenteeism was not significantly different between treatment groups at W40 (52W treatment).

Discussion: Compared to PBO, miri treatment provided statistically significant improvements in work productivity and activity impairment as measured by the WPAI:UC. Improvements were observed during induction and maintenance therapy in pts with moderately-to-severely active UC who had failed prior conventional or biologic therapies.

	Activity Impairment of All Participants		Absenteeism from Work of Employed Participants		Presenteeism at Work of Employed Participants		Overall Work Impairment of Employed Participants
	LSM Change from BL (SE)	LSM Diff¹ (SE)	LSM Change from BL (SE)	LSM Diff¹ (SE)	LSM Change from BL (SE)	LSM Diff¹ (SE)	LSM Change from BL (SE)	LSM Diff¹ (SE)
Induction Period Change from Baseline (Week 12)
PBO IV Q4W (N=294)	-12.90 (1.41)		-3.45 (1.75)		-13.94 (1.75)		-14.91 (1.99)
Miri 300 mg IV Q4W (N=868)	-20.90 (0.87)	-8.01 (1.57)***	-7.88 (1.03)	-4.43 (1.95)*	-19.25 (1.03)	-5.31 (1.95)**	-20.65 (1.16)	-5.74 (2.20)**
Maintenance Period Change from Induction Baseline of Miri Induction Responders (Week 40; 52 Weeks of Continuous Therapy)
PBO SC Q4W (N=179)	-22.91 (1.77)		-10.78 (1.68)		-19.82 (1.98)		-22.59 (2.26)
Miri 200 mg SC Q4W (N=365)	-32.46 (1.35)	-9.55 (1.98)***	-12.85 (1.28)	-2.07 (1.93)	-29.42 (1.51)	-9.60 (2.28)***	-31.72 (1.73)	-9.13 (2.61)***

Abbreviations: BL=Baseline; IV=intravenous; LSM=least squares mean; LSM Diff=least squares mean difference; Miri=mirikizumab; N=number of participants in the analysis population; PBO=placebo; Q4W=every 4 weeks; SC=subcutaneous; SD=standard deviation; SE=standard error

¹The LSM Diff is the least squares mean change from baseline in WPAI:UC scores of participants receiving mirikizumab minus the LSM change from baseline in WPAI:UC scores of participants receiving placebo.

*p< 0.05

**p< 0.01

***p< 0.001

Table: Changes from Baseline in Work Productivity and Activity Impairment Questionnaire: Ulcerative Colitis Scores at Week 12 and Week 40 (52 Weeks of Continuous Treatment)

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. B0350 - Mirikizumab Improves Work Productivity and Activity Impairment Questionnaire Scores in Moderately-to-Severely Active UC: The LUCENT-1 and LUCENT-2 Randomized, Double-Blind, Placebo-Controlled Phase 3 Studies, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.