P1159Pooled analysis of efficacy and safety of once-daily oral obefazimod in European patients from the ABTECT 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 Phase 2 induction and 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. We present a pooled analysis of the efficacy and safety of Obe in the European subgroup of pts enrolled in ABTECT trials. Methods The multicenter, randomized, double-blind, placebo-controlled ABTECT trials enrolled pts with moderate-to-severe UC (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 limit on the number of prior advanced therapy inadequate responses. 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 post-hoc analysis focuses on subgroups of pts from Western (WE) and Eastern Europe (EE). Efficacy endpoints evaluated included clinical remission, clinical response, endoscopic improvement, symptomatic remission, and histo-endoscopic mucosal improvement. All p-values are nominal. Treatment emergent adverse events (TEAEs), serious TEAEs and dropout rates were evaluated. Results Of the 1272 pts randomized in the ABTECT trials, 285 were WE pts and 479 were EE pts. Baseline demographics and disease characteristics were generally balanced between treatment groups and comparable between regions with the exception of a higher proportion of WE pts had prior inadequate response to advanced therapy (81.8-86.9%) vs EE pts (19.1-27.2%). In the pooled analysis, a higher proportion of WE pts receiving Obe-50 vs. PBO achieved clinical remission (Obe-50-PBO difference: 13.3%, p = 0.0095) and also met all other endpoints with nominal significance (Table). Among EE pts both Obe-25 and Obe-50 met all efficacy endpoints vs. PBO with nominal significance. TEAEs were reported more frequently in WE pts (Obe-50: 78.8%, Obe-25: 67.5%, PBO: 64.8%) than in EE pts (Obe-50: 48.0%, Obe-25: 30.4%, PBO: 43.6%). Headache was the most common TEAE (Obe-25: 12.4%, Obe-50: 21.0%, PBO: 5.5%) and rates of serious TEAEs were comparable across treatment groups (2.2-3.4%). TEAE leading to study discontinuation was more frequent with Obe-50 (4.7%) vs PBO (2.2%). No signal was observed for serious/severe and opportunistic infections or malignancies. Conclusion In the European population included in the ABTECT induction trials, obefazimod demonstrated consistent efficacy and safety comparable to the overall study population. 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: Scaldaferri, Franco: Consultancy fee/board for Janseen, Takeda, Pfizer, MSD, Sandoz, Galapagos, Celltrion, Ferring, Abbvie, Lilly, Alfasigma, Abivax Seidler, Ursula: Consultant for Abivax, Amgen, Janssen speaker for Abivax, Janssen and research grants from Abbvie, Abivax, Janssen, Boehringer Ingelheim, Eli Lilly, Gilead Sciences, MSD, Roche. Tretón, Xavier: Personal Fees: Lectures and advisory board : Abbvie, Calltrion, MSD, johnson&Johnson, Takeda, Amgen, Alphasigma, Lilly Other: participations: Thabor Therapeutics 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. 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 Howaldt, Stefanie: Dr. Howaldt served as the Principal Investigator for the presented study sponsored by Abivax 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. 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. 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. Tilg, Herbert: Consultant for Abivax Cataldi, Fabio: Employee of Abivax Jacobstein, Doug: Employee of Abivax Rabbat, Chris: Employee of Abivax Shan, Kevin: Employee of Abivax Cicala, Michele: No conflict of interest