P0892Impact of prior inadequate response to advanced therapy (ATIR) on the efficacy of obefazimod in patients with moderately to severely active ulcerative colitis: results in subgroups including or excluding patients with prior JAK-IR from ABTECT Phase 3 induction trials

Abstract Background Obefazimod (Obe) is an oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and has shown efficacy in patients (pts) with moderately to severely active ulcerative colitis (UC) 1-3. In Phase 3 ABTECT-1 NCT05507203 and ABTECT-2 NCT05507216 8-week induction trials, Obe achieved clinically meaningful improvements in all clinical, endoscopic and histologic endpoints regardless of prior advanced therapy inadequate response (ATIR), including highly refractory pts with ≥4 prior treatment failures. This pooled analysis evaluates the impact of ATIR with and without pts with prior inadequate response to JAK inhibitors (JAK-IR) on the efficacy of Obe in the two ABTECT trials. Methods The multicenter, randomized, double-blind, placebo-controlled ABTECT trials enrolled pts with moderate-to-severe UC (modified Mayo score (MMS)≥ 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 (with no upper limit) including corticosteroids, immunosuppressants, biologics, S1P receptor modulators and/or JAK inhibitors (JAKi). 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. Rates of clinical remission and response, endoscopic improvement, symptomatic remission and response were compared across subgroups of all ATIR pts and the subgroup of ATIR pts without JAK-IR in any line of therapy (ATIR/Non-JAK-IR). Results Among pts enrolled in the ABTECT trials, 602 were ATIR and 478 ATIR/Non-JAK-IR. In both ATIR pts and in ATIR/Non-JAK-IR, Obe-50 led to nominally significant improvements at week 8 in clinical remission, clinical response, endoscopic improvement and symptomatic endpoints, compared with PBO (Table). Improvements were also observed with Obe-25, but with less consistency across efficacy endpoints. Conclusion In this pooled analysis of ABTECT trials, obefazimod showed rapid and nominally significant efficacy across clinical, endoscopic, and symptomatic endpoints in all ATIR pts. Similar outcomes were observed in the ATIR subgroup excluding JAK-IR in any line of therapy. References: 1. Vermeire S, et al. JCC 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: Baert, Filip J.: Grant: AbbVie, Amgen, EG, J & J, Takeda. Personal Fees: AbbVie, Abivax, Alpha Sigma, Arena, BMS,,Celltrion, Eli Lilly, Falk, Ferring, Fresenius, Galapagos, J & J, Pfizer, Sandoz, Takeda, Vifor. Rubin, David T.: Grant support: Takeda Pharmaceuticals Consultant: Abbvie, Abivax SA, Altrubio, Athos Therapeutics, Inc, Bristol-Myers Squibb, Celltrion, Connect BioPharma, Eli Lilly & Co., Genentech (Roche) Inc., Iterative Health, Janssen Pharmaceuticals, Johnson & Johnson, Merck & Co., Mirador, Odyssey Therapeutics, Pfizer, Sanofi, Spyre, Takeda Pharmaceuticals, Vedanta Biosciences, and Ventyx. Wolanski, Lukasz: No conflict of interest 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 Cataldi, Fabio: Employee of Abivax Jacobstein, Doug: Employee of Abivax Rabbat, Chris: Employee of Abivax Shan, Kevin: Employee of Abivax de Sa Rolim, Alexander: No conflict of interest D’Amico, Ferdinando: Grant: ECCO fellowship grant 2020 ECCO grant 2021 Personal Fees: F D’Amico has served as a speaker for Abbvie, Alfasigma, Ferring, Lilly, Sandoz, Janssen, Fresenius Kabi, Galapagos, Giuliani, MSD, Pfizer, Takeda, Tillotts, and Omega Pharma he also served as an advisory board member for Abbvie, AnaptysBio, Ferring, Fresenius Kabi, Galapagos, Janssen, Lilly, MSD, Takeda, and Nestlè. 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