P985 Efficacy and safety of de-escalation from 50 mg to 25 mg of oral, once-daily, obefazimod for the third and fifth year of open-label maintenance treatment in patients with moderately to severely active ulcerative colitis (UC): An interim analysis

Abstract

Abstract Background Obefazimod is an investigational, oral, once-daily, small molecule which enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with ulcerative colitis (UC) [1]. Obefazimod demonstrated efficacy and safety in patients with UC at week-8 in a Phase 2a and Phase 2b, double-blind, placebo-controlled induction trials [2] and their subsequent open-label maintenance (OLM) studies [3]. Methods Patients with UC who received 50 mg of oral, once-daily, obefazimod for approximately four years in the Phase 2a OLM study and approximately two years in the Phase 2b OLM study, provided they met the eligibility criteria (Mayo Endoscopic subscore = 0 or 1), were given the option to transition to a subsequent open-label maintenance study in which they were administered a daily dose of 25 mg of obefazimod for up to 2 years. This interim analysis, conducted with cut-off date of July 31, 2023, reports the findings of a cohort of patients who completed their week 48 visit. Results As of the cut-off date, there were 71 eligible patients, of whom 8 (11%) discontinued prior to week 48 and 63 (89%) completed their 48-week visit. An as observed analysis indicated a disease control rate of 84% (defined as a stable or improved Modified Mayo Score) (Table 1). The levels of fecal calprotectin were <250 and <150 µg/g for 93% (42/45) and 82% (37/45) of patients with available FCP values, respectively. In total, 39/76 subjects (51.3%) reported at least one treatment emergent adverse event (TEAE). The most frequent TEAEs (≥ 5%) were COVID-19 (7.9%) and ulcerative colitis (6.6%). No new safety findings were identified over these 48 weeks. Conclusion One year after dose de-escalation to a daily regimen of 25 mg of obefazimod, favorable outcomes in disease control were observed among patients with UC who demonstrated endoscopic improvement (ES<1) after 2-4 years of 50 mg od. No new safety signals have emerged for a duration of up to five years of treatment with once-daily obefazimod.