P0690 Impact of concomitant use of corticosteroids on efficacy and safety of obefazimod at week 8 of induction trials in patients with moderately to severely active ulcerative colitis: results from the ABTECT-1 and ABTECT-2 Phase 3, double-blind, placebo-controlled 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. Here, we evaluated the effect of concomitant corticosteroid (CS) use on the efficacy and safety of obefazimod in pts enrolled in 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 (CS, 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. Pts were categorized based on concomitant CS use at baseline (CS-yes/CS-no), the dose of which was held constant through week 8. Efficacy endpoints were clinical remission/response, endoscopic improvement/remission, symptomatic remission, and histo-endoscopic mucosal improvement (HEMI). All p-values are nominal. Treatment emergent adverse events (TEAEs), serious TEAEs and study discontinuation rates were examined. Results Among pts in ABTECT trials, 508 used concomitant CS at baseline through week 8 (CS-yes) and 764 did not (CS-no). In both trials, baseline demographics and disease characteristics were similar between treatment groups, regardless of baseline CS status. In the pooled analysis, a higher proportion of pts receiving Obe-25 or Obe-50 vs. PBO achieved clinical remission across CS-yes and CS-no subgroups (Obe-50-PBO difference: CS-yes: 12.5%; CS-no: 19.1%; Obe-25-PBO difference: CS-yes: 8.3%; CS-no: 16.4%) and met all other endpoints across CS-yes and CS-no subgroups with nominal significance (Table). Among CS-yes pts, TEAEs occurred in 56.5%, 45.0%, and 49.2% of those receiving Obe-50, Obe-25, and PBO, respectively. For CS-no pts, rates were 62.8%, 51.3%, and 51.8%. Headache was the most frequent TEAE when treated with Obe across both subgroups. Among CS-yes and CS-no pts, rates of serious TEAEs and TEAE leading to study discontinuation were comparable between treatments. No signal was observed for serious, severe, or opportunistic infections or malignancies. Conclusion In both ABTECT induction trials, Obe demonstrated consistent efficacy and safety irrespective of baseline CS status. 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 & Hepatology. 2022; 7: 1024-1035 Conflict of interest: Tretón, Xavier: Personal Fees: Lectures and advisory board : Abbvie, Celltrion, MSD, Johnson & Johnson, Takeda, Amgen, Alphasigma, Lilly, Pfizer Other: participations: Thabor Therapeutics 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 Seidler, Ursula: No conflict of interest Jonaitis, Laimas: No conflict of interest Cataldi, Fabio: Employee of Abivax Jacobstein, Doug: Employee of Abivax Rabbat, Chris: Employee of Abivax Shan, Kevin: Employee of Abivax 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. Lee, Scott: Consultant for Johnson and Johnson, Abbvie, Merck, Spyre, Celltrion, BI 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.