B0377 - Mirikizumab Significantly Improves Abdominal Pain in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies

Monday, October 24, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

EL

Edward V. Loftus, Jr., MD, FACG

Mayo Clinic College of Medicine and Science
Rochester, Minnesota

Edward V. Loftus, MD, FACG¹, Theresa Hunter Gibble, PhD², Alison Potts Bleakman, MA, PhD², Xingyuan Li, PhD², Nathan Morris, PhD², Emily Hon, MD², Vipul Jairath, MBChB, DPhil³
¹Mayo Clinic College of Medicine and Science, Rochester, MN; ²Eli Lilly and Company, Indianapolis, IN; ³Western University, London, ON, Canada

Introduction: Abdominal pain (AP) is a frequent and burdensome symptom in patients (pts) with ulcerative colitis (UC).¹ Mirikizumab (miri; IL-23p19 inhibitor) demonstrated efficacy vs placebo (PBO) in adult pts with moderately-to-severely active UC in randomized, double-blind, phase 3 LUCENT-1 (induction/NCT03518086) and LUCENT-2 (maintenance/NCT03524092) studies.^2.3 Here, we report the effect of miri vs PBO on AP.

Methods: In the induction study, pts (N=1162) were randomized 3:1 to receive intravenous (IV) miri 300 mg or PBO every 4 weeks (Q4W). Pts who achieved clinical response with miri at W12 (N=544) of induction were re-randomized 2:1 to subcutaneous (SC) miri 200 mg or PBO Q4W through W40 in the maintenance study. Pts recorded “worst AP in the past 24 hours” each day using an 11-point AP Numeric Rating Scale (NRS; 0 = no pain; 10 = worst possible pain) on an electronic diary. AP improvement (AP NRS score ≥30% improvement from baseline [BL] in pts with BL AP NRS ≥3) was evaluated. The Cochran-Mantel-Haenszel test was used to compare the proportion of pts achieving AP improvement with missing data imputed as nonresponse.

Results: As early as W4 (miri 43.0% vs PBO 33.7%; risk difference [95% CI]: 9.7 [2.8–16.6], p=0.007) of the induction study, a significant reduction from BL of at least 30% in AP NRS score was observed in the miri-treated pts vs PBO through W12 (66.4% vs 49.2%; 17.4 [10.3–24.6], p< 0.001). In the maintenance study, a greater percentage of miri-treated pts maintained AP NRS improvement compared to PBO. The separation started at W16 (79.2% vs 69.2%; 9.0 [0.5–17.5], p=0.034) and sustained through W40 (76.2% vs 47.2%; 27.4 [18.3–36.4], p< 0.001; Figure).

Discussion: Miri provided early (W4) and sustained improvement (through W40) of AP compared with PBO in pts with moderately-to-severely active UC.

¹Dulai PS, et al. Development of the symptoms and impacts questionnaire for Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther. 2020;51(11):1047–66.

²G 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:i028–29.

³M 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.

Figure: Figure. The proportion of patients with AP NRS ≥30% improvement at A. induction and B. maintenance in patients with Abdominal Pain NRS score ≥3 at induction baseline. *p<0.05; **p<0.001 vs. placebo
Weekly measures were calculated by averaging data from daily diary entries of AP NRS for a 7-day period. Baseline value for both induction and maintenance was calculated from daily diary entries the week prior to W0 of induction.
Abbreviations: AP NRS, Abdominal Pain Numeric Rating Scale; IV, intravenous; miri, mirikizumab; PBO, placebo; SC, subcutaneous

Disclosures:

Edward Loftus: AbbVie – Consultant, Grant/Research Support. Amgen – Consultant, Grant/Research Support. Arena Pharmaceuticals – Consultant. Boehringer Ingelheim – Consultant. Bristol-Myers Squibb – Consultant, Grant/Research Support. Calibr – Consultant. Celgene – Consultant, Grant/Research Support. Eli Lilly – Consultant. Genentech – Consultant, Grant/Research Support. Gilead – Consultant, Grant/Research Support. Iterative Scopes – Consultant. Janssen – Consultant, Grant/Research Support. Morphic – Consultant. Ono Pharma – Consultant. Pfizer – Consultant, Grant/Research Support. Protagonist – Consultant. Receptos – Grant/Research Support. Robarts Clinical Trials – Grant/Research Support. Scipher Medicine – Consultant. Sun Pharma – Consultant. Surrozen – Consultant. Takeda – Consultant, Grant/Research Support. Theravance – Grant/Research Support. UCB – Consultant, Grant/Research Support.

Theresa Hunter Gibble: Eli Lilly and Company – Employee.

Alison Potts Bleakman: Eli Lilly and Company – Employee.

Xingyuan Li: Eli Lilly and Company – Employee.

Nathan Morris: Eli Lilly and Company – Employee.

Emily Hon: Eli Lilly and Company – Employee.

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.

Edward V. Loftus, MD, FACG¹, Theresa Hunter Gibble, PhD², Alison Potts Bleakman, MA, PhD², Xingyuan Li, PhD², Nathan Morris, PhD², Emily Hon, MD², Vipul Jairath, MBChB, DPhil³. B0377 - Mirikizumab Significantly Improves Abdominal Pain in Patients With Moderately-to-Severely Active Ulcerative Colitis: Results From the Phase 3 LUCENT-1 Induction and LUCENT-2 Maintenance Studies, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.