P0636 Impact of obefazimod treatment on histologic and combined histologic and endoscopic outcomes in patients with moderately to severely active ulcerative colitis: results from the Phase 2b open-label maintenance study

Abstract Background Obefazimod is an investigational, oral, once-daily (QD), small molecule which enhances expression of microRNA-124 and demonstrated efficacy and safety in patients with moderately to severely active ulcerative colitis (UC) in a placebo-controlled, Phase 2b induction trial and the subsequent 96-week open-label maintenance (OLM) study [1, 2]. Here, we report proportions of patients that met endoscopic, histologic and combined histologic-endoscopic outcomes at the end of the induction trial (baseline of OLM), Weeks 48 (W48) and 96 (W96) of the OLM study. Methods Patients received obefazimod 25mg, 50mg or 100mg once daily (QD) or placebo during induction and could enter the optional 96-week OLM study irrespective of their clinical response to receive obefazimod 50mg QD. Rectal or sigmoidal biopsies were collected during endoscopy at OLM baseline, W48 and W96 to evaluate treatment effect on histopathology scores using the Geboes score. Endoscopic improvement (endoscopic sub-score ≤1), endoscopic remission (endoscopic sub-score = 0), histologic improvement (Geboes histologic score ≤3.1), histologic remission (Geboes histologic score <2.0), histo-endoscopic mucosal improvement (HEMI, Geboes histologic score ≤ 3.1 and endoscopic improvement) and histo-endoscopic mucosal remission (HEMR, Geboes histologic score <2.0 and endoscopic remission) were evaluated using as observed analysis (i.e. only patients with both endoscopic and histologic outcome for each endpoint) and non-responder imputation (NRI) for patients missing either endoscopy data and/or histology data. Results There were 217 patients that completed the induction trial and entered OLM. In a data-as-observed analysis, the proportions of patients achieving endoscopic improvement increased from 49% at OLM baseline to 73% at W48, and 78% at W96. The proportion of patients achieving histologic improvement rose from 59% at OLM baseline to 85% at W48, and 89% at W96; 39% achieved HEMI at OLM baseline, and increased to 69% at W48, and 74% at W96 (Table 1). Similar trends were observed for remission endpoints as well as in the NRI analysis. Conclusion In this Phase 2b OLM study, patients with moderately to severely active UC treated with obefazimod experienced clinically meaningful improvements in endoscopic, histologic, and combined histologic-endoscopic outcomes with proportions of patients meeting these endpoints consistently increasing from OLM baseline through W96. These data suggest sustained and progressive therapeutic benefits over time. References 1. Vermeire S, et al. J Crohns Colitis. 2023; 17: 1689-16972. 2. Vermeire S, et al. The Lancet Gastroenterology & Hepatology. 2022; 7: 1024-1035.