Abx464 (Obefazimod) in Patients with Moderate-to-Severe Ulcerative Colitis: An Interim 48-Week Safety and Efficacy Analysis from an Ongoing 96-Week Open-Label Maintenance Phase 2b Study

ABSTRACT

Introduction: ABX464 (obefazimod) is an oral small molecule that modulates inflammation by upregulating a specific anti-inflammatory micro- RNA (miR-124). ABX464 has demonstrated safety and efficacy in patients with moderate-to-severe ulcerative colitis (UC) in a randomized, placebocontrolled, phase 2b induction study (NCT04023396)1. This analysis presents interim data at week 48 after enrollment in the open-label (OL) maintenance study. Aims & Methods: During the 16-week induction Phase 2b, patients received placebo or obefazimod 25mg, 50mg or 100mg once daily (od) and, irrespective of their clinical response, could enter the OL 96-week maintenance study with obefazimod 50mg od. Patients were enrolled into this study from January 13, 2020. Here we present data from an interim analysis cut-off date on Feb 13, 2022. Patients were followed monthly for safety and efficacy. Non-responder imputation (NRI) was used for missing efficacy data. All subjects were assessed for safety treatment emergent adverse events (TEAEs), TEAEs leading to study discontinuation, serious adverse events (SAEs). Result(s) Of 222 patients who completed the phase2b induction study, 217 (97.7%) were enrolled in the OL maintenance study. 33/217 (15.2%) patients dropped out prior to week 48, mainly for UC worsening (10/33). All dropouts were considered as treatment failures for this interim analysis. Main efficacy results are presented in the table below. Among the 96 patients with no clinical response after induction, 42.7% achievedde novo clinical remission at week 48 of the OL maintenance study. Among the 52 patients with clinical remission after induction, 73.1% maintained clinical remission at week 48. In total, 139/217 subjects (64.1%) reported at least one TEAE. TEAEs leading to study discontinuation were reported in 15 subjects (6.9%) and serious adverse events (SAEs) were reported in 17 subjects (7.8%). The most frequent TEAEs (>= 5%) were headache (11.5%), COVID-19 (10.1%), ulcerative colitis (6.5%) and nasopharyngitis (5.9%). No new safety risks were identified over these initial 48 weeks. Conclusion(s) Results from this 48-week interim analysis of the OL maintenance Phase 2b study confirmed excellent long-term efficacy of obefazimod 50mg od in clinical responders and non-clinical responders after induction as well as a favorable long-term safety profile.