Abstract Background Obefazimod (Obe) is an oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and shows efficacy in patients (pts) with moderately to severely active ulcerative colitis (UC) 1-3. In Phase 3 ABTECT 8-week induction trials (NCT0550720, NCT05507216) Obe achieved clinically meaningful improvements in clinical, endoscopic and histologic endpoints. Early treatment with more efficacious drugs offers a better chance to achieve durable remission in UC. However, many pts with long term UC remain undertreated, underscoring the need for safe and effective therapeutic agents that work in both, earlier and later disease. We report the impact of baseline disease duration on Obe efficacy in pts with UC enrolled in the two Phase 3 ABTECT trials. Methods The ABTECT trials were randomized, double-blind, placebo-controlled studies that included pts with moderate-to-severe UC (defined as 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. For this post-hoc analysis, pts were stratified based on baseline disease duration since UC diagnosis: 2 years (BDD2), 2 to 10 years (BDD2-10), or ≥ 10 years (BDD≥10). Endpoints included clinical remission/response, endoscopic improvement/remission, symptomatic response/remission, and histo-endoscopic mucosal improvement (HEMI). All p-values are nominal. Results Of the 1272 randomized and treated pts in ABTECT trials, 250 pts had BDD2, 662 pts had BDD2-10 and 360 pts had a BDD≥10. Baseline demographics and disease characteristics were overall equivalent between treatment groups, and comparable between BDD groups except a higher proportion of BDD2-10 and BDD≥10 pts having endoscopic score of 3 and prior inadequate response to advanced therapy vs BDD2 pts. In a pooled analysis, a higher proportion of pts receiving Obe-25 or Obe-50 versus PBO achieved clinical remission across BDD subgroups (Obe-50-PBO difference: BDD2: 20.6%; BDD2-10: 17.8%; BDD≥10: 12.5%; Obe-25-PBO difference: BDD2: 13.6%; BDD2-10: 13.2%; BDD≥10: 13.0%) and met most endpoints across BDD subgroups with nominal significance (Table). A numerical trend of greater efficacy with shorter disease duration was observed. Conclusion In the ABTECT induction trials of obefazimod for moderately to severely active UC, shorter or longer disease duration was not associated with differences in clinically meaningful improvements across clinical, endoscopic, and histo-endoscopic endpoints. 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: D’Haens, Geert: Grant: Pfizer, BMS, Johnson and Johnson, Abbvie, Alimentiv BV, Eli Lilly, Takeda, Prometheus Laboratories Personal Fees: Abbvie, Abivax, Agomab, Alimentiv, Anaptys Bio, AstraZeneca, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Galapagos, Glaxo Smith Kline, Dr Falk Pharma, Pfizer, Johnson and Johnson, Merck, Mirador, Polpharma, Procise Diagnostics, Prometheus Biosciences, Sorriso Pharma, Spyre, Takeda, Ventyx 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. Kempinski, Radoslaw: Lecture fees from AbbVie, Aboca S.p.A. Societa Agricola, Ferring, Eli Lilly and company grant/research support from Takeda, Johnson & Johnson Innovative Medicine. Kiełtucki, Jacek: No conflict of interest Baláz, Jozef Vladimir: Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Abbvie, Eli Lilly, Takeda Support for attending meetings and/or travel: Abbvie, SOBI Pharma, Takeda Participation on a Data Safety Monitoring Board or Advisory Board: Abbvie, Eli Lilly, Takeda 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 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 Cataldi, Fabio: Employee of Abivax Jacobstein, Doug: Employee of Abivax Rabbat, Chris: Employee of Abivax Shan, Kevin: Employee of Abivax Yarur, Andres: Personal Fees: Consultant for Takeda, Pfizer, Roche, Merck, Abbvie, Eli Lilly. Bristol Myers Squibb, Celltrion, Johnson and Johnson.
D’Haens et al. (Thu,) studied this question.