DOP12 Efficacy and safety of obefazimod in UC patients at weeks 48 and 96 of an open-label maintenance study among clinical responders at week 8 of the Phase 2b induction trial

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 moderately to severely active ulcerative colitis (UC) [1]. Obefazimod demonstrated efficacy and safety in patients with UC at week-8 in a placebo-controlled, Phase 2b induction trial and in the subsequent open-label maintenance (OLM) study [2]. Here we report efficacy and safety at weeks 48 and 96 among patients who achieved clinical response at week 8 of the double-blind induction trial and compared efficacy to the overall study population. Methods Patients received placebo or obefazimod 25mg, 50mg or 100mg once daily (od) during the Phase 2b, induction trial and, irrespective of their clinical response, could enter the optional 96-week OLM study with obefazimod 50mg od. Patients were followed monthly for safety and efficacy. This analysis focuses on efficacy and safety among patients who reached clinical response (decrease from baseline in the Modified Mayo score (MMS) ≥ 2 points and ≥30% from baseline, plus a decrease in rectal bleeding sub-score (RBS) ≥ 1 or an absolute RBS ≤ 1) at week 8 of double-blind induction and continued treatment in the OLM. Results Among the 217 patients who participated in the OLM, 57% (124/217) achieved clinical response at week 8 of the induction trial. Within this subgroup, 66% (82/124) and 60% (74/124) achieved clinical remission at weeks 48 and 96, respectively. Clinical response was achieved by 86% (107/124) and 77% (95/124), endoscopic improvement was achieved by 70% (87/124) and 64% (79/124), and endoscopic remission was achieved by 38% (47/124) and 42% (52/124) at weeks 48 and 96, respectively. The proportions of patients achieving these efficacy endpoints in this subpopulation were numerically higher than those observed in the overall study population (Table 1). No new safety findings were observed in this sub-population during the OLM. Conclusion A substantial proportion of patients who reached clinical response at week 8 of the induction study achieved clinical efficacy endpoints at week 48 and 96 of the open-label maintenance study. Among these patients, nearly 8 out of 10 maintained clinical response, and 6 of 10 achieved durable clinical remission for up to 96 weeks of treatment with 50 mg of once-daily obefazimod.