Abstract
Abstract Background Obefazimod is an investigational, oral, once-daily (QD), small molecule that enhances expression of microRNA-124 and is currently in phase 3 clinical trials for the treatment of patients with UC [1]. Obefazimod demonstrated efficacy and safety at Week 8 in two double-blind, placebo-controlled induction trials and ensuing open-label maintenance (OLM) studies [2, 3]. In a subsequent OLM study utilizing a lower dose, interim analysis indicated efficacy in patients with varying exposure lengths. Here, we report efficacy and safety in a subset of patients that completed both week 48 (W48) and week 96 (W96) endoscopies. Methods Patients with UC who received obefazimod 50mg QD for approximately four years in the Phase 2a OLM study and approximately two years in the Phase 2b OLM study, provided they met eligibility criteria (Mayo Endoscopic subscore = 0 or 1), were enrolled in a subsequent OLM study utilizing a reduced dose of 25mg QD for up to an additional 54 months. This interim analysis reports findings among the subset of patients who had completed W48 and W96 with all components of the modified Mayo score (MMS) available at the cutoff date (11SEP2024). Results As of the cutoff date, there were 73 patients who have all 3 components of the MMS available at baseline (ie, last before the first dose of 25mg QD), W48 and W96, with a mean age of 44.2 years; 37% were female, and mean UC disease duration of 10.6 years at the entry to this OLM study. At baseline of this OLM study, prior to dose de-escalation, 92% (67/73) of patients were in symptomatic remission. Following dose de-escalation, the proportion of patients achieving symptomatic remission was maintained at or above 92% for all quarterly study visits through W96. Similarly, median fecal calprotectin (FCP) levels were below 70 µg/g at each visit from baseline through W96 (min-max: 50.5-69.0 µg/g) (Figure 1). No new safety findings were identified over these 96 weeks. Conclusion In a patient population treated for 2-4 years in OLM studies with 50mg QD, a high percentage of patients who were compliant with the two annual endoscopy visits maintained efficacy measures for two additional years on a reduced dose of 25mg QD. FCP levels below 70 µg/g are generally associated with mucosal healing or remission. Safety was consistent with prior studies, with no new findings. These data further support the long-term efficacy and safety of a lower obefazimod maintenance dose.
Published Version
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