Obefazimod in patients with moderate-to-severely active ulcerative colitis: efficacy and safety analysis from the 96-week open-label maintenance phase 2b study

Background and Aims: Obefazimod is an oral small molecule that selectively enhances the expression of a single micro-RNA (miRNA), miR-124. Obefazimod has demonstrated safety and efficacy in patients with moderate-to-severely active ulcerative colitis (UC) in a phase 2b induction trial. This analysis presents the 2-year outcome data of the open-label maintenance (OLM) study. Methods: Patients received placebo or obefazimod 25, 50, or 100 mg once-daily (od) during the induction trial and, irrespective of their clinical response, could enter the 96-week OLM study with obefazimod 50 mg od. Safety was monitored through monthly visits in the first year and quarterly visits in the second year. Efficacy was assessed at weeks 48 and 96 using nonresponder imputation (NRI) for missing data. Results: Of 222 eligible patients, 217 were enrolled and 164 (75.6%) completed week 96 of the OLM study. Clinical response was achieved at weeks 48 and 96 in 177 (81.6%) and 158 (72.8%) patients and clinical remission in 119 (54.8%) and 114 (52.5%) of patients. A total of 133 (61.3%) and 128 (59.0%) patients showed endoscopic improvement, and 72 (33.2%) and 78 (35.9%) endoscopic remission. In total, 148/217 patients (68.2%) reported at least 1 treatment-emergent adverse event (TEAE). The most frequent TEAEs were COVID-19 (14.3%), headache (11.5%), UC (7.8%), and nasopharyngitis (6.9%). No new safety risks emerged over 96 weeks. Conclusions: The 96-week OLM study supports the long-term efficacy and favorable safety profile of obefazimod 50 mg od. A phase 3 program with obefazimod in patients with moderate-to-severe UC is ongoing.