P0713Improvements in patient-reported bowel urgency and nocturnal bowel movements among patients with moderately to severely active ulcerative colitis (UC) treated with obefazimod induction therapy: pooled results from the 8-week ABTECT-1 and ABTECT-2 Phase 3, double-blind, placebo-controlled induction trials

Abstract Background Obefazimod (Obe) is an investigational, oral, once-daily (QD), small molecule which enhances expression of microRNA-124 for the treatment of moderately to severely active ulcerative colitis (UC). Patients (pts) with UC suffer frequent bowel movements accompanied with bowel urgency (BU) and nocturnal bowel movements (NBM) which negatively impact quality of life. Here we report efficacy data from two Phase 3, 8-week, induction trials on these patient-reported symptoms. Methods In the Phase 3 ABTECT 1 NCT05507203 and ABTECT 2 NCT05507216 trials, pts with UC were randomized 2:1:1 to receive Obe 50 mg QD (Obe-50), Obe 25 mg QD (Obe-25), or placebo (PBO) QD for 8 weeks. Pts reported BU and NBM using a single-item question yes/no in a daily electronic diary. BU and NBM scores were based on the total number of days a subject reported BU or NBM over the 7 days leading up to the timepoint (scores range 0-7). Pts that received at least 1 dose and had baseline BU 0 and NBM0 were included in the analysis of proportions. Responders were defined as pts who had no BU or NBM over the closest 3 consecutive days or 4 non-consecutive days in the 7 days closest to the timepoint. All p-values are nominal. Results 1272 pts were randomized and treated in ABTECT-1 (n = 636) and ABTECT-2 (n = 636); 1128 pts had BU and 976 pts had NBM data at baseline. At baseline, pts reported 6.1, 6.2, and 6.1 days/week with BU in the Obe-50, Obe-25, and PBO groups, respectively. At Week 8, Obe-treated pts reported fewer days of BU vs PBO: 3.2, 3.2, and 4.4 in the Obe-50, Obe-25, and PBO groups, respectively (Obe-50: Δ-1.38 and Obe-25: Δ-1.34 vs PBO, p 0.0001). Improvements were seen as early as Week 2. At Week 8, a greater proportion of Obe pts reported no BU: 37.0% for Obe-50 and 37.2% for Obe-25 vs 18.1% for PBO (Obe-50: Δ19.2, Obe-25: Δ18.9, p 0.0001). At baseline, pts reported 5.0, 5.2, and 5.0 nights/week of NBM in the Obe-50, Obe-25, and PBO groups, respectively. At Week 8, Obe-treated pts reported fewer nights with NBM vs PBO: 2.0, 2.1, and 3.4 in the Obe-50, Obe-25, and PBO groups, respectively (Obe-50: Δ-1.45 and Obe-25: Δ-1.44 vs PBO, p 0.0001). Improvements were seen as early as Week 2. At Week 8, a greater proportion of Obe pts reported no NBM: 47.6% for Obe-50 and 43.5% for Obe-25 vs 24.7% for PBO (Obe-50: Δ19.1, Obe-25: Δ23.1, p 0.0001) (See Table). Results for BU and NBM were consistent across both trials. Conclusion Obe markedly improved BU and NBM in pts with moderately to severely active UC across both ABTECT induction trials with improvements observed as early as 2 weeks. Conflict of interest: 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 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 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. Sparrow, Miles P.: Educational grants or research support – Gilead, Celltrion Speaker’s fees – Janssen, Abbvie, Ferring, Takeda, Pfizer, Celltrion, Eli Lilly, Dr. Falk Pharma Advisory boards or consultancy fees – Janssen, Takeda, Pfizer, Celgene, Abbvie, MSD, Emerge Health, Gilead, BMS, Celltrion, Eli Lilly, Alimentiv Hlavaty, Tibor: Personal Fees: Pfizer, Abbvie, Takeda, Janssen Pharmaceuticals, Amgen Magro, Fernando: Fernando Magro served as speaker and received honoraria from Abbvie, Arena, Biogen, Bristol-Myers Squibb, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Pfizer, Lilly, Merck Sharp & Dohme, Sandoz, Takeda, UCB, Vifor. Nancey, Stéphane: board membership and lecturing fees from Abbvie, Takeda, Celltrion Healthcare, Pfizer, Galapagos, Johnson & Jonshon, Lilly, Fresenius, Amgen, Medac, MSD. Rabbat, Chris: Employee of Abivax Fine, Jennifer T: Employee of Abivax Shan, Kejia: employee of Abivax Dolan, Chantal M.: Paid Consultant for Genentech, F. Hoffmann-La Roche AG, Abivax, Regenxbio, Boerhinger Ingelhiem, Pharmacoevidence, Mcure B Jacobstein, Doug: Employee of Abivax Cataldi, Fabio: Employee of Abivax Armuzzi, Alessandro: Grant: Abbvie, Biogen, MSD, Pfizer, Takeda Personal Fees: Abbvie, Abivax, AG Pharma, Alfa Sigma, Astra Zeneca, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Giuliani, Johnson & Johnson, Lionhealth, MSD, Nestlé, Novartis, Pfizer, Protagonist Therapeutics, Roche, Samsung-Bioepis, Sandoz, Sanofi, Takeda, Teva Pharmaceuticals, Tillots Pharma Non-financial Support: Abbvie, Janssen, Merck, Pfizer, Sofar, Takeda