P0928Improvements in patient-reported work productivity and activity impairment 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 being investigated for the treatment of moderately to severely active ulcerative colitis (UC). Patients (pts) with UC experience symptoms which negatively impact their ability to work.1 Here we report the impact of 8-week Obe treatment on the patient-reported Work Productivity and Activity Impairment Questionnaire for adults with UC (WPAI:UC) in pts enrolled in the ABTECT trials. 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. Work productivity was measured using the WPAI:UC that measures impairments in paid and unpaid work using 6 questions across 4 domains (absenteeism, presenteeism, activity impairment and overall work impairment). WPAI:UC scores are expressed as percentage impairment. Meaningful within patient change (MWPC) thresholds were defined as: absolute decrease of 7.3 in overall work impairment, ≥6.5 decrease for absenteeism, ≥6.1 decrease for presenteeism, and ≥8.5 decrease for activity impairment. All p values are nominal. Results At baseline, 1272 pts were randomized and treated in ABTECT-1 (n = 636) and ABTECT-2 (n = 636); 1153 pts had WPAI:UC data. At baseline, 59.1% of pts in the Obe-50 group, 65.7% of pts in the Obe-25 group and 60.3% of PBO pts reported overall impairment while working. Abstenteeism was reported by 21.9%, 27.6%, and 21.3% of pts in the Obe-50, Obe-25, and PBO groups, respectively. Presenteeism was reported by 50.2%, 55.0%, and 51.4% of pts in the Obe-50, Obe-25, and PBO groups, respectively. Activity impairment was reported by 56.7%, 58.0%, and 59.1% of pts in the Obe-50, Obe-25, and PBO groups, respectively. At week 8, a smaller proportion of pts treated with Obe reported overall work impairment compared to PBO: 36.2% of Obe-50 pts and 34.6% of Obe-25 pts vs 47.8% of PBO pts (Obe-50: Δ-11.03, Obe-25: Δ-13.21, both p = 0.0002). Similar improvements were observed for pts treated with Obe vs PBO with nominal significance across most WPAI:UC domains. At week 8, greater proportions of pts treated with Obe reported a MWPC on overall work impairment relative to PBO: 66.3% for Obe-50 and 71.8% for Obe-25 vs 56.9% of PBO (Obe-50: Δ9.64, p = 0.06; Obe-25: Δ15.13, p 0.05). Greater proportions of Obe-treated pts also achieved a MWPC for the presenteeism and activity impairment domains vs PBO (Table). Conclusion Obe markedly improved work productivity and reduced activity impairment in pts with moderately to severely active UC across both ABTECT induction trials. Reference: 1. Kim et al. Qual Life Res. 2024;33(5):1373-1387 Conflict of interest: Tilg, Herbert: Consultant for Abivax Dulai, Parambir: Grant: Takeda, Bristol Meyer Squibb, Merck, Genentech, Geneoscopy Personal Fees: Abbvie, Abivax, Alimentiv, Bristol Meyer Squibb, Boehringer Ingelheim, Celltrion, Cristcot, Genentech, Geneoscopy, Janssen, Lilly, Merck, Pfizer, Sanofi, Takeda Skybalo, Svitlana: Has received speaker fees from Abivax Neshta, Viacheslav: Dr. Neshta served as the Principal Investigator for the presented study sponsored by Abivax. Howaldt, Stefanie: Dr. Howaldt served as the Principal Investigator for the presented study sponsored by 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. Gregus, Milos: Patricipation in clinical studies/ company sponsored grants: Eli Lilly Slovakia, AbbVie, Celltrion, Takeda, Roche Speaker / lecturer: AbbVie, Janssen, Pfizer Expert advisor: AbbVie, Eli Lilly, Takeda, Zentiva Rabbat, Chris: Employee of Abivax Fine, Jennifer T: Employee of Abivax Shan, Kejia: Employee of Abivax Dolan, Chantal M.: Paid Consultant for Genentech, Roche, Abivax, Regenxbio, Boerhinger Ingelhiem, Pharmacoevidence, Mcure Bio Jacobstein, Doug: Employee of Abivax Cataldi, Fabio: Employee of Abivax Siegmund, Britta: Grant: Pfizer Other: Consultant: Abbvie, Abivax, Boehringer Ingelheim, Bristol Myers Squibb, Dr. Falk Pharma, Eli Lilly, Endpoint Health, Galapagos, Janssen/Johnson & Johnson, Materia Prima, MSD, Pfizer, Takeda, Wedbush Securities. Speaker: Abbvie, AlfaSigma, Bristol Myers Squibb, CED Service GmbH, Dr. Falk Pharma, Eli Lilly, Ferring, Galapagos, Janssen/Johnson & Johnson, MD Education, MSD, Pfizer, Tr1xBio.