P0952Impact of baseline Mayo endoscopic subscore on the efficacy of once-daily oral obefazimod in moderately to severely active ulcerative colitis: week 8 results from the two Phase 3 ABTECT induction trials

Abstract Background Obefazimod (Obe) is an oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and has been studied in two Phase 2 induction trials and subsequent open-label maintenance studies 1-3 in patients (pts) with moderately to severely active ulcerative colitis (UC). In Phase 3 ABTECT-1 NCT05507203 and ABTECT-2 NCT05507216 8-week induction trials, Obe achieved clinically meaningful improvements in clinical, endoscopic and histologic endpoints. Baseline disease characteristics can influence clinical outcomes and are important to consider when optimizing UC treatment. Here, we report the efficacy of Obe in pts stratified by baseline Mayo endoscopic subscore (MES) from the two ABTECT induction trials. Methods The multicenter, randomized, double-blind, placebo-controlled ABTECT trials enrolled pts with moderate-to-severe UC (modified Mayo score≥ 5, with rectal bleeding sub-score (RBS) ≥ 1 and centrally read endoscopic score ≥2) who had inadequate response, loss of response, or intolerance to at least one prior therapy (corticosteroids, immunosuppressants, biologics, S1P receptor modulators and/or JAK inhibitors) with no limit on the number of prior inadequate response to advanced therapies. Pts were randomized 2:1:1 to Obe 50 mg QD (Obe-50), Obe 25 mg QD (Obe-25) or placebo (PBO) for 8 weeks. This post-hoc analysis categorized pts by baseline MES = 2 (MES2) or MES = 3 (MES3). Efficacy endpoints evaluated clinical remission/response, endoscopic improvement/remission, symptomatic response/remission, and histo-endoscopic mucosal improvement (HEMI). All p-values are nominal. Results Among the 1272 randomized and treated pts in ABTECT trials, 40.2% (511) were MES2 and 59.8% (761) were MES3. In both trials, baseline demographics and disease characteristics were similar between treatment groups, regardless of baseline MES. In the pooled analysis, higher proportion of pts receiving Obe-25 or Obe-50 versus PBO achieved clinical remission in both the MES 2 (Obe-25-PBO difference: 20.2%, p 0.0001; Obe-50-PBO difference: 21.7%, p 0.0001) and MES 3 (Obe-25-PBO difference: 8.7%, p = 0.0001; Obe-50-PBO difference: 12.5%, p 0.0001) subgroups, and similar trends were observed across all other endpoints (Table). Overall, the proportions of pts achieving efficacy endpoints were generally numerically lower in the MES 3 subgroup compared with the MES 2 subgroup. Conclusion In both ABTECT induction trials, obefazimod demonstrated clinical meaningful improvements irrespective of baseline MES. Numerically greater efficacy rates were observed in pts with baseline MES2 vs MES3. References: 1. Vermeire S, et al. J Crohns Colitis. 2023; 17: 1689-1697 2. Vermeire S, et al. Gastroenterology 2021; 160: 2595-2598 3. Vermeire S, et al. The Lancet Gastroenterology 7: 1024-1035. Conflict of interest: Peyrin-Biroulet, Laurent: CONSULTING Abbvie, Abivax, Adacyte, Alimentiv, Alfasigma, Amgen, Apini, Banook, BMS, Celltrion, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, LifeMine, Medac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Par’ Immune, Pfizer, Prometheus, Roche, Roivant, Samsung, Sandoz, Sanofi, Sorriso, Spyre, Takeda, Teva, ThirtyfiveBio, Tillots, Vectivbio, Vedanta, Ventyx. LECTURE Abbvie, Alfasigma, Amgen, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Iterative Health, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots Sands, Bruce E: Grant: Janssen, Bristol Myers Squibb, Pfizer Personal Fees: Abivax SA Abbvie Aclaris Therapeutics, Inc. Adiso Therapeutics Agomab Therapeutics Alfasigma SpA Alimentiv Amgen AMT AnaptysBio Arena Pharmaceuticals Artizan Biosciences AstraZeneca Biora Therapeutics Boehringer-Ingeleim Bristol Myers Squibb Calibr Celltrion, Inc. ClostraBio Connect Biopharm Cytoki Pharma EcoR1 Capital Eli Lilly and Company Enthera Equilium, Inc. Evommune Ferring Fresenius Kabi Galapagos Genentech, Inc. Gilead Sciences GlaxoSmithKline Gossamer Bio Imhotex Immunic 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 Kyowa Kirin, Inc. Merck & Co. Microba Microbiotica Limited MiroBio Morphic Therapeutic MRM Health NV Pfizer, Inc. Progenity Prometheus Biosciences Prometheus Laboratories Protagonist Therapeutics, Inc. Q32 Bio Surrozen Synlogic Operating Company, Inc. Takeda Target RWE Televant Teva Branded Pharmaceutical Products R&D TLL Pharmaceutical VectivBio AG Ventyx Biosciences Non-financial Support: Janssen, Pfizer, Lilly, Takeda, Bristol Myers Squibb Other: Stock/Stock Options from Ventyx Biosciences Armuzzi, Alessandro: Consulting fees from AbbVie, Abivax, Alfa Sigma, Astra Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Enthera, Ferring, Galapagos, Gilead, Giuliani, Janssen, Lionhealth, MSD, Nestlé, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sanofi, Sandoz, Takeda, Teva Pharmaceuticals, Tillots Pharma Speaker’s fees from AbbVie, Abivax, AG Pharma, Alfa Sigma, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, Lionhealth, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, Teva Pharmaceuticals Research support from Biogen, MSD, Takeda, and Pfizer Non-financial support from Abbvie, Janssen, MSD, Pfizer, Takeda Cataldi, Fabio: Employee of Abivax Jacobstein, Doug: Employee of Abivax Rabbat, Chris: Employee of Abivax Shan, Kevin: Employee of Abivax Toeroek, Helga: Helga P Török reports consultant fees from AbbVie, Calypso Biotech, Celtrion, Immunic, Johnson and Johnson, Pharmacosmos and Takeda Pharma and lecture honoraria from Abbvie, Biogen, BMS, Falk Foundation, Galapagos, Johnson and Johnson, Pfizer, Pharmacosmos, and Takeda Pharma Nancey, Stéphane: board membership and lecturing fees from Abbvie, Takeda, Celltrion Healthcare, Pfizer, Galapagos, Johnson & Jonshon, Lilly, Fresenius, Amgen, Medac, MSD. D’Haens, Geert: Grant: Pfizer, BMS, Johnson and Johnson, Abbvie, Alimentiv BV