Efficacy and Safety of Obefazimod in Patients With Ulcerative Colitis at Week 48 of an Open-Label Maintenance Study Among Clinical Nonresponses at Week 8 of the Phase 2b Induction Trial

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). 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. Here we present efficacy and safety among patients who did and those that did not achieve clinical response at week 8 of the double-blind induction trial.
Methods:
Patients received placebo or obefazimod 25 mg, 50 mg, or 100 mg 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 50 mg od. Patients were followed monthly for safety and efficacy. This analysis evaluates efficacy (at week 48) and safety (through week 96) among patients who achieved and those who did not achieve 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 (CR group), and 43% (93/217) did not (NCR group). Proportions of patients achieving efficacy endpoints were numerically higher within the CR group than those observed in NCR group. At week 48, 66% of CR patients and 40% of NCR patients achieved clinical remission; 86% of CR patients and 75% of NCR patients achieved clinical response; endoscopic improvement was achieved by 70% of CR patients and by 50% of NCR patients, and endoscopic remission was achieved by 38% of CR patients and 27% of NCR patients. At week 8, median FCP was lower in CR patients (253 µg/g) than in NCR patients (923 µg/g). By week 48, median FCP was 83 µg/g for CR patients and 97 µg/g for NCR patients. 64% and 46% of patients had FCP < 250 µg/g among CR and NCR patients, respectively, with 56% and 43% achieving FCP < 150 µg/g. There was no significant difference in the safety profile between these 2 subpopulations.
Conclusions:
Substantial proportions of patients treated with obefazimod 50 mg od achieved clinical outcomes at week 48 of an open label maintenance study, irrespective of whether they achieved clinical response at week 8 of the prior induction trial. Patients achieving clinical response at week 8 of the induction trial consistently showed higher efficacy rates throughout the 48-week open-label maintenance trial. The safety profile remains consistent over time, regardless of treatment response at week 8.