P0563Mirikizumab Demonstrated Sustained and Durable Long-Term Efficacy and Favorable Safety in Week 52 Endoscopic Responders with Crohn’s disease: 3-year VIVID-2 Open-Label Extension Interim Results

Abstract Background VIVID-2 (NCT04232553) is an ongoing open-label extension study evaluating the long-term efficacy and safety of mirikizumab (MIRI), a selective IL-23p19 monoclonal antibody, in patients with moderately to severely active Crohn’s disease (CD). We present results from patients randomised to MIRI in the Phase 3 VIVID-1 study (NCT03926130) who attained endoscopic response at W52 and continued to receive MIRI maintenance dosing for a third year in VIVID-2. Methods In VIVID-1, the MIRI group received induction with 900 mg intravenously (IV) at weeks (W) 0, 4, and 8, then 300 mg subcutaneously (SC) every 4W. W52 endoscopic responders (≥50% reduction from baseline in Simple Endoscopic Score for CD SES-CD) continued the same MIRI SC dosing in VIVID-2. Outcomes assessed at W152 of MIRI treatment included Crohn’s Disease Activity Index (CDAI) remission, corticosteroid-free (CSF) CDAI remission, bowel urgency (BU) clinically meaningful improvement (CMI), BU remission, and inflammatory biomarkers normalisation. Safety was assessed from the first dose in VIVID-2 through W152. Discontinuations or missing data were handled using observed cases (OCs) and modified nonresponder imputation (mNRI). Results Among MIRI W52 endoscopic responders (N = 251) (OC%/mNRI%), 87.9%/76.8% achieved CDAI remission, 86.8%/75.7% achieved CSF CDAI remission, 75.0%/66.1% achieved BU CMI, and 53.8%/47.2% achieved BU remission at W152 (Figure 1a). Of patients who achieved the specified endpoint at W52, 92.4%/82.8% maintained CDAI remission, 91.2%/81.1% maintained CSF CDAI remission, 82.1%/72.7% maintained BU CMI, and 71.7%/64.0% maintained BU remission at W152 (Figure 1b). Of patients who did not achieve the specified endpoint at W52, 72.5%/58.4% gained CDAI remission, 73.9%/62.1% gained CSF CDAI remission, 53.8%/46.4% gained BU CMI, and 28.1%/24.8% gained BU remission at W152 (Figure 1c). From W52 to W152, improvements in induction-maintenance inflammatory biomarkers C-reactive protein and fecal calprotectin further decreased in MIRI W52 endoscopic responders (Figure 2). The overall safety profile remained consistent with no increase from year one of treatment in exposure-adjusted incidence rates of long-latency events such as MACE, malignancies, overall infections, or serious infections. Conclusion MIRI treatment in W52 endoscopic responders demonstrated sustained and durable long-term clinical efficacy of MIRI in patients with moderately to severely active CD. High maintenance rates of remission outcomes and additional improvement in biomarker values were observed after three years of MIRI treatment. The safety data was consistent with the known safety profile of MIRI. Conflict of interest: Laharie, David: Personal Fees: Board, consulting and lecture fees from Abbvie, Alfasigma, Amgen, Biocon, Celltrion, Ferring, Fresenius-Kabi, Johnson & Johnson, Lilly, MSD, Pfizer, Sandoz and Takeda Clemow, David: Employee and stockholder of Eli Lilly and Company. Sands, Bruce E: Grant: Janssen, Bristol Myers Squibb, Pfizer Personal Fees: Abivax SA Abbvie Adiso Therapeutics Agomab Therapeutics Alimentiv Amgen AnaptysBio AstraZeneca Biora Therapeutics Boehringer-Ingeleim Bristol Myers Squibb Celltrion, Inc. ClostraBio Cytoki Pharma EcoR1 Capital Eli Lilly and Company Enthera Equilium, Inc. Ensho Therapeutics Evommune Ferring Galapagos Genentech, Inc. Gilead Sciences GlaxoSmithKline Gossamer Bio Imhotex Immunyx Pharma Ltd. Index Pharmaceuticals Innovation Pharmaceuticals Janssen Janssen Biotech Janssen Pharmaceutica NV Janssen Research & Development, LLC Janssen Scientific Affairs, LLC Janssen-Cilag PTY, Ltd. Johnson & Johnson Kaleido Kallyope Kyowa Kirin, Inc. Merck & Co. Microba Microbiotica Limited Mirador Therapeutics Morphic Therapeutic MRM Health NV Palisade Therapeutics Pfizer, Inc. Prometheus Biosciences Prometheus Laboratories Protagonist Therapeutics, Inc. Q32 Bio Sanofi Sorriso Therapeutics Surrozen Takeda Target RWE Teva TLL Pharmaceutical Tr1x Union Therapeutics Ventyx Biosciences Non-financial Support: Janssen, Pfizer, Lilly, Takeda, Bristol Myers Squibb Other: Stock/Stock Options from Ventyx Biosciences Hozak, Rebecca: Employee and Stock holder for Eli Lilly and Company Barnes, Edward: Grant: Eli Lilly, Salix/Bausch Health Personal Fees: Consultant for Abbvie, Boomerang, Eli Lilly, Johnson & Johnson, Pfizer, Sanofi, Takeda, and Target RWE. D’Haens, Geert: Grant: Pfizer, BMS, Johnson and Johnson, Abbvie, Alimentiv BV, Eli Lilly, Takeda, Prometheus Laboratories Personal Fees: Abbvie, Abivax, Agomab, Alimentiv, Anaptys Bio, AstraZeneca, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Galapagos, Glaxo Smith Kline, Dr Falk Pharma, Pfizer, Johnson and Johnson, Merck, Mirador, Polpharma, Procise Diagnostics, Prometheus Biosciences, Sorriso Pharma, Spyre, Takeda, Ventyx Gupta, Prashant: Employee and Stockholder of Eli Lilly and Company Hisamatsu, Tadakazu: Grant support: Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., Boston Scientific Corporation, Kissei Pharmaceutical Co. Ltd. Consulting: Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, Janssen Pharmaceutical K.K., Pfizer Inc., Eli Lilly, Gilead Sciences, Bristol Myers Squibb, Abivax, MSD, Chugai. Lecture fee: Mitsubishi Tanabe Pharma Corporation, AbbVie GK, EA pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Kissei Pharmaceutical Co. Ltd. Gandhi R, Arul: Employee and Stockholder of Eli Lilly and Company Kelly, Colleen: has been an advisory board member for: Eli Lilly and Company Lopes, Michelle: I currently work at Eli Lilly as a Global Patient Safety Physician Moses, Richard: Employee of Eli Lilly and Company. Regueiro, Miguel: Advisory Boards and Consultant (both) for Abbvie, Johnson and Johnson, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celltrion, Roche, Merck, Sanofi, Biocon, Abavax