P0804Impact of prior inadequate response to advanced therapies on early symptomatic improvement with obefazimod induction in moderately to severely active ulcerative colitis: results from the two Phase 3 placebo-controlled 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 all clinical, endoscopic and histologic endpoints regardless of prior inadequate response to advanced therapy (ATIR). Here we report the impact of prior ATIR on early symptomatic improvement with Obe in the ABTECT trials. Methods The multicenter, randomized, double-blind, placebo-controlled ABTECT trials enrolled pts with moderate-to-severe UC (modified Mayo score (MMS)≥ 5, 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, including corticosteroids, immunosuppressants, biologics, S1P receptor modulators and/or JAK inhibitors (JAKi) with no limit on the number of prior ATIR. 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 pooled analysis focuses on proportions of pts achieving symptomatic remission or symptomatic response from week 1 (W1) through week 8 (W8). Pts were categorized as ATIR-No and ATIR-Yes, with the latter further categorized by JAKi IR status (ATIR-Yes/JAKi-No vs. ATIR-Yes/JAKi-Yes). All p-values are nominal. Results Among pts enrolled in the ABTECT trials, 670 were ATIR-No and 602 were ATIR-Yes (478 ATIR/JAKi-No, 124 ATIR/JAKi-Yes). In ATIR-No and ATIR-Yes pts, both Obe-50 and Obe-25 led to clinically meaningfully improvements in symptoms compared with PBO. Compared to PBO, a higher proportion of ATIR-No pts receiving Obe-50 or Obe-25 achieved symptomatic response and symptomatic remission from W2 to W8 (Tables 1 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: Atreya, Raja: RA has served as a speaker, or consultant, or received research grants from AbbVie, Abivax, AlfaSigma, Arena Pharmaceuticals, Astra-Zeneca, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celltrion Healthcare, Dr Falk Pharma, Galapagos, Gilead, GlaxoSmithKline, InDex Pharmaceuticals, Johnson & Johnson, Lilly, Materia Prima, Merck Sharpe & Dohme, Pfizer, Roche Pharma, Takeda Pharma, Viatris. 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 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. Dubinsky, Marla C: Personal Fees: Consultant or Advisory Board: Abbvie, Abivax, Astra Zeneca, BMS, Celltrion, Gilead, Genentech, Janssen, Johnson and Johnson, Lilly, Merck, Pfizer, Prometheus Biosciences, Sanofi, Spyre, Target RWE, Takeda Other: Shareholder, Co-founder, Board of Directors of Trellus Health Co-Founder Mi Test Health 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 Tretón, Xavier: Personal Fees: Lectures and advisory board : Abbvie, Calltrion, MSD, johnson&Johnson, Takeda, Amgen, Alphasigma, Lilly Other: participations: Thabor Therapeutics</jats