DOP71 Efficacy of once-daily, orally administered obefazimod in patients with moderately to severely active UC at weeks 8, 48, and 96 broken down by induction treatment dose

Abstract

Abstract Background Obefazimod (obe) 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]. Obe demonstrated efficacy in patients with UC at week-8 in a phase 2b, double-blind, placebo-controlled, dose ranging, induction trial and in the subsequent open-label maintenance (OLM) study [2]. Methods During the induction Phase 2b trial, patients received placebo or obe 25mg, 50mg or 100mg once daily (od). Irrespective of their clinical response, patients could enter the optional 96-week OLM study with obe 50mg od. Of the 222 eligible patients, 217 continued treatment in the OLM. We examine the efficacy outcomes at weeks 8, 48, and 96, for patients enrolled in the OLM according to their induction dose group. Results Among the 58 patients who initially received obe 25 mg during the induction period, 28% (16/58) achieved clinical remission at week 8. After switching to 50 mg in the OLM, the rate of clinical remission increased to 60% (35/58) at weeks 48 and 96. Similar trends were observed for clinical response (66% (38/58) at week 8, 85% (49/58) at week 48, and 74% (43/58) at week 96), endoscopic improvement (36% (21/58) at week 8, 60% (35/58) at week 48, and 66% (38/58) at week 96), and endoscopic remission (7% (4/58) at week 8, 28% (16/58) at week 48, and 47% (27/58) at week 96). In the group of patients who received obe 50 mg in the induction period (n= 51), 20% (10/51) achieved clinical remission at week 8. After switching to 50 mg in the OLM, the rate of clinical remission increased to 49% (25/51) at week 48 and 96. Similar trends were observed for clinical response and endoscopic improvement (Table 1). Among the 53 patients who received obe 100 mg in the induction period, 28% (15/53) achieved clinical remission at week 8. After switching to 50 mg in the OLM, the rate of clinical remission increased to 55% (29/53) at week 48 and week 96. Similar trends were observed for clinical response and endoscopic improvement (Table 1). Among the 55 patients who received placebo in the induction period, 15% (8/55) achieved clinical remission at week 8. After switching to 50 mg in the OLM, the rate of clinical remission increased to 55% (30/55) at week 48, and 45% (25/55) at week 96. Similar trends were observed for clinical response and endoscopic improvement (Table 1). Conclusion These findings suggest that patients with UC treated with obefazimod 50mg od after the week 8 induction period maintained efficacy and continued to improve, irrespective of their induction dose, as evidenced by higher percentages of patients reaching clinical endpoints at weeks 48 and 96 relative to week 8.