P2205 - Sustained Improvement in Inflammatory Bowel Disease Questionnaire Outcomes in Moderately to Severely Active Ulcerative Colitis with Continued Mirikizumab Treatment in Phase 3 LUCENT-3 Study

Monday, October 23, 2023

10:30 AM – 4:15 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

Bruce E. Sands, MD, MS, FACG

Icahn School of Medicine at Mount Sinai
New York, New York

Bruce E. Sands, MD, MS, FACG¹, Brian G. Feagan, MD², Alessandro Armuzzi, MD, PhD³, Kim McGinnis, CPNP⁴, Keisa Lynch, DNP, APRN, FNP⁵, Theresa Hunter Gibble, PhD, MPH⁴, Jordan Johns, PhD⁴, Corey A. Siegel, MD, MS⁶, Vipul Jairath, MBChB, DPhil²
¹Icahn School of Medicine at Mount Sinai, New York, NY; ²Western University, London, ON, Canada; ³IBD Center, IRCCS Humanitas Research Hospital, Rozzano (Milan); Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Milan, Lombardia, Italy; ⁴Eli Lilly and Company, Indianapolis, IN; ⁵University of Utah School of Medicine, Salt Lake City, UT; ⁶Dartmouth-Hitchcock Inflammatory Bowel Disease Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH

Introduction: Mirikizumab (miri) significantly improved quality of life as evidenced by the Inflammatory Bowel Disease Questionnaire (IBDQ) scores in moderately to severely active ulcerative colitis (UC) during 12-week (W) induction (LUCENT-1) and 40-W maintenance (LUCENT-2) phase 3 studies.¹ IBDQ response and remission rates were significantly higher with miri versus placebo in both studies.¹ Here we report interim results of 104-W of continuous miri therapy on IBDQ outcomes from an ongoing open-label, single-arm, phase 3, multicenter, long-term extension study (LUCENT-3/NCT03519945).

Methods: Patients who completed LUCENT-2 and achieved clinical response or remission after 52-W of continuous miri therapy entered LUCENT-3 and continued to receive miri 200 mg every 4 weeks subcutaneously. Least squares mean change from baseline in IBDQ total and domain scores were evaluated at W104 using an analysis of covariance model. IBDQ response (≥16-point improvement from baseline)¹ and IBDQ remission (IBDQ total score ≥170)¹ rates, stratified by prior biologic failure status, were assessed at W104. Missing data were imputed using modified baseline observation carried forward (IBDQ change from baseline) and non-responder imputation (IBDQ response and remission rates).

Results: Among the 239 patients with clinical response at W52 who entered the LUCENT-3 study, 154 were in clinical remission. Improvements in IBDQ total and domain scores for these patients were sustained at W104 (Figure 1A). IBDQ response at W104 was seen in over 80% of patients and was comparable across ‘biologic failed’ and ‘not biologic failed’ subgroups (Figure 1B). IBDQ remission rates in the clinical response (78.2%) and clinical remission (80.5%) groups were sustained in ‘not biologic failed’ subgroup (80.1% and 83.2%) and were numerically lower in ‘biologic failed’ subgroup (74.0% and 74.5%), respectively (Figure 1C).

Discussion: In the LUCENT-3 extension study, treatment with mirikizumab showed sustained improvement in quality of life up to W104 in patients with moderately to severely active UC with or without prior biologic failure.

¹Sands BE, et al. Mirikizumab improves quality of life in moderately to severely active ulcerative colitis: improvement in inflammatory bowel disease scores in participants of the LUCENT-1 and LUCENT-2 randomized, double-blind, placebo-controlled phase 3 induction and maintenance trials. United European Gastroenterol J. 2022;10(S8):778.

Figure: Figure 1: IBDQ outcomes at W104 of continuous mirikizumab treatment in patients who achieved clinical responsea or remissionb in LUCENT-2 – mITT population : A) LS mean change from baseline in IBDQ total and domain scores (ANCOVA with mBOCF) ; B) IBDQ response rates (≥16-point improvement from baseline) (NRI); and C) IBDQ remission rates (IBDQ total score ≥170) (NRI)

Baseline was defined as the last nonmissing assessment recorded on or prior to the date of the first study drug administration at Week 0 in LUCENT-1 induction study.
*Within-treatment change from baseline p<0.001 calculated using ANCOVA.
aClinical Responders: Patients who achieved ≥2 points and ≥30% decrease from baseline in MMS and a decrease of ≥1 point in the RB subscore from baseline or an RB score of 0 or 1.
bClinical Remitters: Patients who achieved SF subscore = 0 or 1 with ≥1 point decrease from baseline; RB = 0; ES = 0 or 1.
cBiologic failed: Inadequate response, loss of response, or intolerant to a biologic therapy or Janus kinase inhibitors for UC.
dNot biologic failed: Failed conventional treatments (i.e., immunomodulators/corticosteroids); may include some participants who were exposed to but did not fail biologic treatment.

ANCOVA, analysis of covariance; ES, endoscopic subscore; IBDQ, Inflammatory Bowel Disease Questionnaire; LS, least squares; mBOCF, modified baseline observation carried forward; mITT, modified intent-to-treat; MMS, modified Mayo score; NRI, non-responder imputation; RB, rectal bleeding; SE, standard error; SF, stool frequency.

Disclosures:

Bruce Sands: AbbVie – Consultant. Abivax – Consultant, Speaker’s fees. Adiso Therapeutics – Consultant. Alimentiv – Consultant. Amgen – Consultant. Arena pharmaceuticals – Consultant. Artizan Biosciences – Consultant. Artugen Therapeutics – Consultant. AstraZeneca – Consultant. Bacainn Therapeutics – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Consultant. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support, speaking fees and other support. Calibr – Consultant. Celltrion – Consultant. ClostraBio – Consultant. Connect Biopharm – Consultant. Cytoki Pharma – Consultant. Eli Lilly – Consultant, speaking fees and other support. Enthera – Consultant. Evommune – Consultant. Ferring – Consultant. Fresenius Kabi – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. Gossamer Bio – Consultant. HMP Acquisition – Consultant. Imhotex – Consultant. Immunic – Consultant. InDex Pharmaceuticals – Consultant. Innovation Therapeutics – Consultant. Inotrem – Consultant. Ironwood Pharmaceuticals – Consultant. Janssen – Grant/Research Support, consulting and speaking fees and other support. Johnson & Johnson – Consultant. Kaleido Biosciences – Consultant. Kallyope – Consultant. Merck – Consultant. MiroBio – Consultant. Morphic Therapeutics – Consultant. MRM Health – Consultant. OSE Immunotherapeutics – Consultant. Pfizer Inc – Consultant, Grant/Research Support, speaking fees and other support. Progenity – Consultant. Prometheus Biosciences – Consultant. Prometheus Laboratories – Consultant. Protagonist Therapeutics – Consultant. Q32 Bio – Consultant. RedHill Biopharma – Consultant. Sun Pharma – Consultant. Surrozen – Consultant. Synlogic Operating Company – Consultant. Takeda – Grant/Research Support, consulting and speaking fees and other support. Target RWE – Consultant. Theravance Biopharma – Consultant, Grant/Research Support. TLL Pharmaceutical – Consultant. USWM Enterprises – Consultant. Ventyx Biosciences – Consultant, personal fees and stock options for consulting. Viela Bio – Consultant.

Brian Feagan: AbbVie – Advisory Committee/Board Member, Consultant, Speakers Bureau. AbolerIS – Consultant. AgomAB Therapeutics – Consultant. Allianthera – Consultant. Amgen – Advisory Committee/Board Member, Consultant. AnaptysBio – Consultant. Applied Molecular Transport Inc. – Consultant. Arena Pharma – Consultant. Avir – Consultant. Azora Therapeutics – Consultant. Baxter – Consultant. BioJamp – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Boston Pharma – Consultant. Bristol Myers Squibb – Consultant. Celgene/BMS – Advisory Committee/Board Member, Consultant. Connect BioPharma – Consultant. Cytoki – Consultant. Disc Medicine – Consultant. Duality – Consultant. EcoR1 – Advisory Committee/Board Member, Consultant. Eli Lilly – Consultant. Equillium – Consultant. Ermium – Consultant. Everest Clinical Research Corp. – Consultant. Ferring Pharmaceuticals – Consultant. First Wave – Consultant. Galapagos – Consultant. Galen Atlantica – Consultant. Genentech/Roche – Advisory Committee/Board Member, Consultant. Gilead – Consultant. GlaxoSmithKline – Advisory Committee/Board Member, Consultant. Glenmark – Consultant. Gossamer Pharma – Consultant, stock shareholder. Hoffmann-LaRoche – Consultant. Hot Spot Therapeutics – Consultant. Imhotex – Consultant. ImmunExt – Consultant. Immunic Therapeutics – Consultant. Index Pharma – Advisory Committee/Board Member, Consultant. Intact Therapeutics – Consultant. JAKAcademy – Consultant. Janssen – Advisory Committee/Board Member, Consultant, 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 – Advisory Committee/Board Member, Consultant. Mylan – Consultant. Novartis – Advisory Committee/Board Member. OM Pharma – Consultant. Origo BioPharma – Advisory Committee/Board Member, Consultant. Orphagen – Consultant. Otsuka – Consultant. Pandion Therapeutics – Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Play to Know AG – Consultant. Progenity – Advisory Committee/Board Member, Consultant. Prometheus Therapeutics and Diagnostics – Advisory Committee/Board Member, Consultant. Protagonist – Consultant. PTM Therapeutics – Consultant. Q32 Bio – Consultant. Rebiotix – Consultant. RedHill Biopharma – Consultant. Redx – Consultant. Roche – Consultant. Sandoz – Consultant. Sanofi – Consultant. Seres Therapeutics – Consultant. Silverback Therapeutics – Consultant. Surrozen Inc. – Consultant. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau. Teva – Advisory Committee/Board Member, Consultant. Thelium – Consultant. Theravance – Consultant. Tigenix – Consultant. Tillotts Pharma – Advisory Committee/Board Member, Consultant. UCB Pharma – Consultant. VHSquared Ltd. – Consultant. Viatris – Consultant. Western University, Alimentiv Inc – Employee. Ysios – Consultant. Ysopia – Consultant. Zealand Pharma – Consultant.

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 – 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. Nestlè – 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.

Kim McGinnis: Eli Lilly and Company – Employee, Stockholder.

Keisa Lynch: Eli Lilly – Consulting/advisory board fees, Speakers Bureau. Gilead – Grant/Research Support, consulting/advisory board fees, Speakers Bureau. Janssen – consulting/advisory board fees. Pfizer – consulting/advisory board fees.

Theresa Hunter Gibble: Eli Lilly and Company – Employee, stockholder.

Jordan Johns: Eli Lilly and Company – Employee, stockholder.

Corey Siegel: Abbvie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. BMS – Advisory Committee/Board Member, Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant. Fresnius – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant, Grant/Research Support, Consultant/advisory board, speaker for CME activities. Napo Pharmaceuticals – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant, Grant/Research Support, speaker for CME activities. Prometheus Biosciences – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau.

Vipul Jairath: AbbVie – Advisory Committee/Board Member, 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. Astra Zeneca – 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 – 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 – consulting/advisory board fees. Vividion – consulting/advisory board fees.

Bruce E. Sands, MD, MS, FACG¹, Brian G. Feagan, MD², Alessandro Armuzzi, MD, PhD³, Kim McGinnis, CPNP⁴, Keisa Lynch, DNP, APRN, FNP⁵, Theresa Hunter Gibble, PhD, MPH⁴, Jordan Johns, PhD⁴, Corey A. Siegel, MD, MS⁶, Vipul Jairath, MBChB, DPhil². P2205 - Sustained Improvement in Inflammatory Bowel Disease Questionnaire Outcomes in Moderately to Severely Active Ulcerative Colitis with Continued Mirikizumab Treatment in Phase 3 LUCENT-3 Study, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.