Introduction
Mirikizumab (miri), an anti-IL-23p19 antibody, has shown efficacy and safety in treatment of patients (pts) with moderately-to-severely active Crohn's disease (CD) up to Week 52 (W52) in a Phase 2 study (NCT02891226). We further assessed efficacy and safety, extending to W104.
Aims & Methods
At baseline, pts (N=191) were randomized 2:1:1:2 allocation across 4 treatment arms (1000, 600, 200mg miri and placebo (PBO), intravenously (IV) every 4 weeks (Q4W) at W0, W4, and W8). Pts who received miri and achieved ≥1 point improvement in Simple Endoscopic Score for Crohn’s Disease (SES-CD) at W12 were rerandomized 1:1 into double-blind maintenance to either continue IV treatment assignment Q4W (IV-C; N=41) or to 300mg miri subcutaneous (SC) Q4W (IV-SC; N=46) up to W52. W12 endoscopic non-improvers and pts receiving PBO during induction received IV 1000mg miri Q4W from W12-W52. Subjects reported to experience clinical benefit received 300 mg SC from W52 to W104. For analysis purposes, all IV and SC arms were pooled. The clinical and symptom endpoints [Crohn’s Disease Activity Index (CDAI) remission (CDAI Total Score <150) and patient-reported outcomes (PRO) remission (defined as SF ≤2.5 and AP ≤1 and no worse than baseline)] were evaluated among endoscopic improvers at W12 who were rerandomized into maintenance and went onto the extension period (W52-W104) (Table 1). Results were summarized by descriptive statistics with non-responder imputation (NRI).
Results
Of the 127 pts randomized to miri for induction, 68.5% (87/127) achieved endoscopic improvement at W12 and were rerandomized into maintenance. Of the W12 endoscopic improvers, 74 finished W52 maintenance and entered the extension period (W52 - W104) where 68 went on to complete treatment through W104. Among the W12 miri induction endoscopic improvers, CDAI remission rates were 39.0% (16/41) (IV-C) and 56.5% (26/46) (SC) and PRO remission rates were 46.3% (19/41) (IV-C) and 45.7% (21/46) (SC) at W52. One year later, (W104), CDAI remission rates were 66.7% (22/33) (IV-C) and 61.0% (25/41) (SC) and PRO remission rates were 63.6% (21/33) (IV-C) and 46.3% (19/41) (SC). Of the 74 endoscopic improvers who finished W52 maintenance, 6 discontinued between W52 to W104 (1 due to adverse events (AEs), 2 due to lack of efficacy, 1 due to lost to follow-up, and 2 due to withdrawal by subject). Among endoscopic improvers at W12, 4 pts were hospitalized due to CD in the SC group (2 from W12-W52 and 2 from W52-W104) as reported in Table 1. In all pts who received any miri treatment from W52 to W104 (endoscopic improvers, non-improvers, and PBO treated pts), 79.4% (108/136) experienced ≥ 1 treatment-emergent AEs.
Table 1. Week 52 and Week 104 Efficacy and Safety Results in Week 12 endoscopic improvers.
| Table 1 | Week 12 Endoscopic Improversc |
| Week 52 | Week 104 | Week 52 | Week 104 |
Miri IV-C
N=41 | Miri IV-C
N=33 | Miri SC
N=46 | Miri SC
N=41 |
| PRO remissiona, n (%) | 19 (46.3) | 21 (63.6) | 21 (45.7) | 19 (46.3) |
| CDAI remissionb, n (%) | 16 (39.0) | 22 (66.7) | 26 (56.5) | 25 (61.0) |
| Hospitalization events due to CD, n (%) | 0 (0) | 0 (0) | 2 (4.3) | 2 (4.9) |
a PRO remission: defined as SF ≤2.5 and AP ≤1, and no worse than baseline; bCDAI remission: A CDAI score of <150 points; cEndoscopic improvement: ≥1 point improvement in SES-CD at Week 12
Abbreviations: CD = Crohn’s disease; SF = stool frequency; AP = abdominal pain; CDAI = Crohn’s Disease Activity Index; PRO = patient-reported outcomes
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Conclusion
Miri demonstrated durable effectiveness among pts with moderately-to-severely active CD who showed early endoscopic improvement with continued miri dosing up to W104, and with no unexpected safety events. CDAI and PRO remission were sustained through W104, with no differences observed in pts who received either IV-C and SC miri treatments during maintenance and continued into the extension period.
Disclosure
Arthur Kaser: Scientific advisor to AstraZeneca, Janssen J&J, Pfizer, Novartis, Boehringer Ingelheim, Ferring, GlaxoSmithKline, Imhotex, Pandion, Merck, MiroBio, Applied Molecular Transport, Eli Lilly, Glenmark, Galapagos
Bruce E Sands: Received fees for consulting and speaking from Abivax, Bristol Myers Squibb, Janssen, Lilly Pfizer, and Takeda; for consulting from AbbVie; Adiso Therapeutics; Alimentiv; Amgen; Arena Pharmaceuticals; Artizan Biosciences; Artugen Therapeutics; AstraZeneca; Bacainn Therapeutics; Boehringer-Ingelheim; Boston Pharmaceuticals; Calibr; Celltrion Healthcare; ClostraBio; Cytoki Pharma; Connect Biopharma; Entera; Evommune; Fresenius Kabi; Galapagos; Genentech; Gilead Sciences; GlaxoSmithKline; Gossamer Bio; Imhotex; Immunic; Index Pharmaceuticals; Inotrem; Innovation Therapeutics; Ironwood Pharmaceuticals; Kaleido; Kallyope; MiroBio; Morphic Therapeutics; MRM Health; OSE Immunotherapeutics; Progenity; Prometheus Biosciences; Protagonist Therapeutics; Q32 Bio; Redhill Biopharma; Sun Pharma; Surrozen; Synlogic; Target RWE; Teva; Theravance Biopharma; TLL Pharmaceutical; USWM Enterprises; VielaBio: VTA Labs; and personal fees and stock options for consulting from Ventyx Biosciences.
Laurent Peyrin-Biroulet: Personal fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Boerhinger Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestle, Inotrem, Enterome, Allergan, MSD, Roche, Arena, Gilead, Hikma, Amgen, BMS, Vifor, Norgine, Mylan, Lilly, Fresenius Kabi, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera, and Theravance; grants from Abbvie, MSD, and Takeda; and stock options from CTMA.
Vipul Jairath: Consulting/advisory board fees: AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso pharmaceuticals, Takeda, Teva, Topivert, Ventyx, Vividion; speaker’s fees: Abbvie, Ferring, Bristol Myers Squibb, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi
Monika Fischer: Advisor for Abbvie, Eli Lilly, BMS, Pfizer, Ferring, Seres, Speaker for Janssen and BMS, DSMB for Rebiotix/Ferring
Marijana Protic, Zhantao Lin, Rebecca Hozak, Hilde Carlier, and Emily Hon: employees and shareholders of Eli Lilly and Company.
