P0712Integrated summary of safety of obefazimod in 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 rerandomized maintenance studies 1-3 in patients (pts) with moderately to severely active ulcerative colitis (UC). In the two Phase 3 ABTECT induction trials, Obe achieved clinically meaningful improvements in clinical, endoscopic and histologic endpoints. Here we report an integrated safety analysis of Obe in the two ABTECT trials. Methods Treatment emergent adverse events (TEAEs), serious TEAEs, discontinuation rates and primary reasons were assessed in the pooled population from ABTECT-1 NCT05507203 and ABTECT-2 NCT05507216 among pts who received Obe 50 mg QD (Obe-50), Obe 25 mg QD (Obe-25), or placebo (PBO) for 8 weeks, randomized to 2:1:1. Results 1272 pts were randomized and treated in ABTECT-1 (636) and ABTECT-2 (636). Overall, 636 patients received Obe-50, 319 received Obe-25, and 317 received placebo (PBO). Baseline demographics and disease characteristics were comparable across treatment groups with median exposures of 60, 61, and 61 days, respectively (Table). Proportions of pts who reported at least one TEAE were 60.2%, 48.9%, and 50.8% for Obe-50, Obe-25, and PBO, respectively. The overall rates of serious TEAEs for pts were comparable across groups (Obe-50: 3.1%; Obe-25: 2.2%; PBO: 3.2%). TEAEs leading to study discontinuation occurred at similar rates across treatment groups (Obe-50, 4.7%; Obe-25, 1.9%; PBO, 4.1%). The most frequent TEAEs (≥ 3% in obe treated pts and greater than PBO) included headache, nausea, abdominal pain, and an increase in serum lipase. Headache TEAEs were mild, transient, short in duration (median: 2-3 days) and rarely led to discontinuation (0-1.1%). Serious, severe, or opportunistic infections or malignancies were rarely reported. Conclusion This integrated safety analysis of the two completed Phase 3 ABTECT induction trials showed a favorable safety and tolerability profile of obefazimod as observed in Phase 2 trials. 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: Seidler, Ursula: Consultant for AbbVie, Abivax, Amgen, Galapagos, Janssen, Eli Lilly speaker for Abivax, Amgen, Galapagos, Eli Lilly, Janssen and research grants from Abbvie, Abivax, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead Sciences, Galapagos, Janssen, Pfizer, Roche, and Takeda Pharmaceuticals 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 Peyrin-Biroulet, Laurent: Grant: Takeda, Fresenius Kabi, Celltrion, Medac, MSD Personal Fees: Abbvie, Abivax, Adacyte, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, BMS, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par’ Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx, Ysopia. Other: SUPPORT TRAVEL : Abbvie, Alfasigma, Amgen, Celltrion, Connect Biopharm, Ferring, Galapagos, Genentech, Gilead, Gossamer Bio, Janssen, Lilly, Medac, Morphic, MSD, Pfizer, Sandoz, Takeda, Thermo Fischer, Tillots. 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 Atreya, Raja: Personal Fees: AbbVie, Abivax, AstraZeneca, Bristol-Myers Squibb, Celltrion Healthcare, Falk Foundation, Galapagos, Gilead, Johnson & Johnson, Lilly, MSD Sharp & Dohme, Takeda Pharma. 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: No conflict of interest Shan, Kevin: No 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 Dulai, Parambir: Grant: Takeda, Janssen, Pfizer, Abbvie, Polymedco, Buhlmann, Prometheus Personal Fees: Takeda, Janssen, Pfizer, Abbvie, Polymedco, Buhlmann, Prometheus 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. 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