What question did this study set out to answer?

To evaluate the influence of prior inadequate response to different drug classes on the effectiveness of obefazimod in improving symptoms of ulcerative colitis.

January 23, 2026

P0894Impact of prior advanced therapy inadequate response by drug class on symptomatic improvement with obefazimod in patients with moderately to severely active ulcerative colitis: pooled analysis of ABTECT Phase 3 induction trials

Key Points

To evaluate the influence of prior inadequate response to different drug classes on the effectiveness of obefazimod in improving symptoms of ulcerative colitis.
Conducted a pooled analysis of two Phase 3 induction trials (ABTECT-1 and ABTECT-2)
Included patients with moderately to severely active ulcerative colitis and prior inadequate response to therapy
Patients were randomized into treatment groups receiving obefazimod or placebo for 8 weeks
Symptomatic remission and response rates were assessed across different subgroups of prior therapy response
Patients receiving obefazimod-50 showed significantly higher rates of symptomatic remission compared to placebo
Symptomatic improvements were observed as early as the first weeks of treatment
Improvements continued through week 8, with no plateau in symptomatic remission across all subgroups of prior inadequate response

Abstract

Abstract Background Obefazimod (Obe) is an oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and has proven 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 specific classes of ATIR 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. 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 symptomatic remission and symptomatic response were evaluated across subgroups of ATIR pts, including 1 TNF inhibitor only (TNFi-IR), vedolizumab only (Vedo-IR), a TNFi + Vedo (TNFi/Vedo-IR) only, a TNFi + Vedo + ustekinumab (TNFi/Vedo/Uste-IR) only, and ustekinumab (Uste-IR) or a JAK inhibitor (JAK-IR) in any line of therapy. Results Among pts enrolled in the ABTECT trials, 114 were TNFi-IR, 92 were Vedo-IR, 67 were TNFi/Vedo-IR, 42 were TNFi/Vedo/Uste-IR, 156 were Uste-IR, and 124 were JAK-IR. In this pooled analysis, higher proportion of pts receiving Obe-50 versus PBO achieved symptomatic remission and symptomatic response from the first weeks of treatment, with proportions increasing over time, and remaining consistent across all ATIR subgroups (Figs. 1 and 2). For pts receiving Obe-50, symptomatic remission continued to improve through W8, without evidence of a plateau (Fig. 1). Conclusion In this pooled analysis of ABTECT trials, Obe demonstrated symptomatic improvements in pts with UC as early as the first weeks of treatment, irrespective of prior inadequate response to any class of AT. Symptomatic remission continued to increase through W8 across all ATIR subgroups without plateau, indicating potential for additional gains beyond W8. 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: Danese, Silvio: Personal Fees: AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB Inc., Vial, Vifor Lecture fees from Abbvie, Amgen, Ferring Pharmaceuticals Inc., Gilead, Janssen, Mylan, Pfizer, Takeda 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 Heeren, Sonja: Dr. Sonja Heeren has served as a consultant or advisory board member for Alfasigma, Amgen, MSD, Abbvie, Galapagos, Lilly, Janssen, Takeda, Shire, and Pfizer has received speaker honoraria from Abbvie,Alfasigma,, AstroPharma, Galapagos, Falk,Ferring, Gilead, Janssen, Lilly, MSD, Roche, Shire, Stada, Takeda, and Vifor and has acted as a past or present Principal Investigator for studies sponsored by Abbvie, Abivax,Agomab, Alimentiv, Amgen, Boehringer, BioAnaptys, Ferring, Galapagos, Janssen, Lilly, MSD, Merck, Novartis, Roche, Pfizer, Sanofi, Shire, and Takeda. Schnabel, Robert: No conflict of interest Cataldi, Fabio: Employee of Abivax Jacobstein, Doug: Employee of Abivax Rabbat, Chris: Employee of Abivax Shan, Kevin: Employee of Abivax Gregus, Milos: No conflict of interest Sparrow, Miles P.: Educational grants or research support – Gilead, Celltrion Speaker’s fees – Janssen, Abbvie, Ferring, Takeda, Pfizer, Celltrion, Eli Lilly, Dr. Falk Pharma Advisory boards or consultancy fees – Janssen, Takeda, Pfizer, Celgene, Abbvie, MSD, Emerge Health, Gilead, BMS, Celltrion, Eli Lilly, Alimentiv 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.

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