A0396 - Mirikizumab Improves Mental and Physical Health Outcomes in Patients With Moderately to Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies

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 G. Feagan, MD², Theresa Hunter Gibble, PhD³, Kristina A. Traxler, PharmD³, Nathan Morris, PhD³, Xingyuan Li, PhD³, William J. Eastman, MD³, Stefan Schreiber, MD⁴, Vipul Jairath, MBChB, DPhil⁵, Alessandro Armuzzi, MD, PhD⁶
¹Icahn School of Medicine at Mount Sinai, New York, NY; ²Alimentiv, Inc.; Western University, 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: Mirikizumab (miri), an anti-IL-23p19 monoclonal antibody, demonstrated efficacy vs. placebo (PBO) in adult patients (pts) with moderately to severely active ulcerative colitis (UC) in phase 3, randomized, double-blind, PBO-controlled 12-week (W) induction (LUCENT-1/NCT03518086) and 40-W maintenance (LUCENT-2/NCT03524092) studies.^1,2 Here we evaluated the effect of miri vs. PBO on Medical Outcomes Study 36-Item Short Form Health Survey (SF-36; version 2) scores.

Methods: In the induction study, 1162 pts who had an inadequate response/loss of response/intolerance to conventional/biologic therapy were randomized (3:1) to receive miri 300 mg IV (N=868) or PBO (N=294) every 4 weeks (Q4W). Pts who achieved clinical response with miri at W12 in the induction study (miri clinical responders; N=544) were re-randomized (2:1) to miri 200 mg subcutaneous (N=365) or PBO (N=179) Q4W through W40 (i.e., W52 of continuous therapy) in the maintenance study. Least squares mean (LSM) change from baseline in physical (PCS) and mental (MCS) component scores, and 8 domain scores (physical functioning, role-physical, role-emotional, bodily pain, vitality, social functioning, mental and general health) of the SF-36 survey were evaluated at W12 and W40. Treatment comparisons were made using analysis of covariance.

Results: During the induction period, significant improvements in PCS (LSM difference vs. PBO [95% CI]: 2.07 [1.21, 2.93]; p< 0.001) and MCS (1.60 [0.56, 2.63]; p=0.002), and all domain scores (p< 0.05) of SF-36 were achieved with miri vs. PBO at W12. These improvements in SF-36 scores were sustained throughout the maintenance period with significant improvements seen with miri vs. PBO group in PCS (2.30 [1.12, 3.49]; p< 0.001) and MCS (1.48 [0.13, 2.82]; p=0.031), and 6/8 domain scores (p< 0.05) at W40 (Table).

Discussion: Miri significantly improves SF-36 mental and physical component scores in patients with moderately to severely active UC during induction (W12) and maintenance (W40).

¹G D’Haens et al. Efficacy and safety of mirikizumab as induction therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-1 study. J Crohn's Colitis, 2022;16(1):i028–i029.

²M Dubinsky, et al. Efficacy and safety of mirikizumab as maintenance therapy in patients with moderately to severely active ulcerative colitis: results from the phase 3 LUCENT-2 study. Abs. 867e. Digestive Disease Week, May 21-24, 2022.

	Induction (W12 analysis)				Maintenance (W40 analysis) Miri clinical responder
	LSM (SE) change from baseline^†		LSM Diff (95% CI) vs. PBO	p-value	LSM (SE) change from baseline^†		LSM Diff (95% CI) vs. PBO	p-value
	PBO IV (N=294)	Miri 300 mg IV (N=868)	LSM Diff (95% CI) vs. PBO	p-value	PBO SC (N=179)	Miri 200 mg SC (N=365)	LSM Diff (95% CI) vs. PBO	p-value
PCS	3.90 (0.393)	5.97 (0.242)	2.07 (1.21, 2.93)	< 0.001	6.66 (0.541)	8.97 (0.412)	2.30 (1.12, 3.49)	< 0.001
MCS	3.42 (0.472)	5.02 (0.291)	1.60 (0.56, 2.63)	0.002	5.54 (0.611)	7.02 (0.465)	1.48 (0.13, 2.82)	0.031
Domain scores
Physical Functioning	6.57 (0.950)	10.16 (0.585)	3.59 (1.51, 5.67)	< 0.001	10.82 (1.221)	13.97 (0.928)	3.16 (0.48, 5.84)	0.021
Role-Physical	10.50 (1.304)	17.21 (0.803)	6.71 (3.86, 9.57)	< 0.001	18.51 (1.667)	26.14 (1.266)	7.63 (3.97, 11.28)	< 0.001
Role-Emotional	5.25 (1.135)	9.06 (0.701)	3.81 (1.33, 6.30)	0.003	10.35 (1.338)	12.95 (1.019)	2.60 (−0.34, 5.54)	0.083
Bodily Pain	13.40 (1.218)	18.43 (0.751)	5.03 (2.37, 7.70)	< 0.001	20.93 (1.663)	26.12 (1.263)	5.19 (1.54, 8.84)	0.005
Vitality	10.38 (1.059)	14.72 (0.652)	4.34 (2.02, 6.65)	< 0.001	16.85 (1.493)	21.54 (1.133)	4.70 (1.42, 7.97)	0.005
Social Functioning	11.69 (1.254)	16.74 (0.772)	5.05 (2.30, 7.79)	< 0.001	17.25 (1.487)	23.95 (1.129)	6.70 (3.44, 9.96)	< 0.001
Mental Health	6.55 (0.887)	9.56 (0.548)	3.00 (1.06, 4.94)	0.002	10.25 (1.233)	12.93 (0.940)	2.67 (−0.04, 5.38)	0.053
General Health	7.03 (0.959)	12.30 (0.592)	5.27 (3.17, 7.37)	< 0.001	14.23 (1.362)	19.83 (1.035)	5.59 (2.61, 8.58)	< 0.001

Table: Change From Baseline (ANCOVA with mBOCF*) in SF-36 Physical and Mental Component Scores and Domain Scores at W12 and W40 (Modified Intent-to-treat Population)
*Patients with missing values had their last value carried forward, with the exception that patients who discontinued due to an adverse event had their baseline value carried forward.
†Baseline for both Induction and Maintenance is defined as the last non-missing assessment recorded on or prior to the date of the first study drug administration at Visit 1 of Induction.
ANCOVA, analysis of covariance; CI, confidence interval; Diff, difference; IV, intravenous; LSM, least squares mean; MCS, mental component score; mBOCF, modified baseline observation carried forward; miri, mirikizumab; PBO, placebo; PCS, physical component score; SC, subcutaneous; SE, standard error; SF-36, medical outcomes study 36-Item short-form health survey; W, week.

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 – Consultant, Member of the scientific advisory board, Speakers Bureau. AbolerIS – Consultant. AgomAB Therapeutics – Consultant. Alimentiv Inc – Employee. Allianthera – Consultant. Amgen – Consultant, Member of the scientific advisory board. AnaptysBio – Consultant. Applied Molecular Transport Inc. – Consultant. Arena Pharma – Consultant. Avir – Consultant. Azora Therapeutics – Consultant. BioJamp – Consultant. Biopharma – Consultant. Biora Therapeutics – Consultant. Boehringer-Ingelheim – Consultant, Member of scientific advisory board. Boston Pharma – Consultant. Boxer – Consultant. Celgene/BMS – Consultant, Member of scientific advisory board. Connect BioPharma – Consultant. Cytoki – Consultant. Disc Medicine – Consultant. Duality – Consultant. EcoR1 Capital – Consultant, Member of the scientific advisory board. Eli Lilly and Company – Consultant. Equillium – Consultant. Ermium – Consultant. Everest Clinical Research Corp. – Consultant. Ferring – Consultant. First Wave – Consultant. Galapagos – Consultant. Galen Atlantica – Consultant. Genentech/Roche – Consultant, Member of scientific advisory board. Gilead – Consultant. Glenmark – Consultant. Gossamer Pharma – Consultant, Stock Shareholder. GSK – Consultant, Member of the scientific advisory board. Hoffmann-LaRoche – Consultant. Hot Spot Therapeutics – Consultant. Imhotex – Consultant. ImmunExt – Consultant. Immunic Therapeutics – Consultant. Index Pharma – Consultant, Member of the scientific advisory board. Intact Therapeutics – Consultant. JAKAcademy – Consultant. Janssen – Consultant, Member of scientific advisory board, Speakers Bureau. Japan Tobacco Inc. – Consultant. Kaleido Biosciences – Consultant. L.E.K. Consulting – Consultant. Landos Biopharma – Consultant. Leadiant – Consultant. LifeSci Capital – Consultant. Lument AB – Consultant. Millennium – Consultant. MiroBio – Consultant. Morphic Therapeutics – Consultant, Member of the scientific advisory board. Mylan – Consultant. Novartis – Member of the scientific advisory board. OM Pharma – Consultant. Origo BioPharma – Consultant, Member of scientific advisory board. Orphagen – Consultant. Otsuka – Consultant. Pandion Therapeutics – Consultant. Pfizer – Consultant, Member of the scientific advisory board. Play to Know AG – Consultant. Progenity – Consultant, Member of the scientific advisory board. Prometheus – Member of scientific advisory board. Prometheus Therapeutics and Diagnostics – Consultant. Protagonist – Consultant. PTM Therapeutics – Consultant. Q32 Bio – Consultant. Rebiotix – Consultant. RedHill – Consultant. REDX – Consultant. Roche – Consultant. Sandoz – Consultant. Sanofi – Consultant. Seres Therapeutics – Consultant. Silverback Therapeutics – Consultant. Surrozen Inc. – Consultant. Takeda – Consultant, Member of the scientific advisory board, Speakers Bureau. Teva – Consultant, Member of the scientific advisory board. Thelium – Consultant. Theravance – Consultant. Tigenix – Consultant. Tillotts Pharma – Consultant, Member of the scientific advisory board. UCB Pharma – Consultant. VHsquared Ltd. – Consultant. Viatris – Consultant. Western University – Employee. Ysios – Consultant. Ysopia – Consultant. Zealand Pharma – Consultant.

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.

William Eastman: 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.