Oral APX3330, a Ref-1 Inhibitor, Slows Progression of Diabetic Retinopathy on a Binocular DRSS Person-Level Scale

Abstract

Purpose : To evaluate the efficacy of APX3330, an oral, small molecule inhibitor of Ref-1, in preventing progression of Diabetic Retinopathy using a binocular 17-step DRSS person-level scale

Methods : This is a post-hoc analysis of data from ZETA-1, a multi-center, randomized, placebo-controlled, double-masked, Phase 2 clinical trial that included 103 subjects with Diabetic Retinopathy Severity Scale (DRSS) scores of 47, 53, or 61 without center-involved diabetic macular edema (CI-DME) in the study eye randomized 1:1 to receive 600 mg APX3330 or placebo. A post-hoc analysis was performed in subjects without CI-DME and with DRSS scores of 43, 47, or 53 in both eyes, using a binocular 17-step DRSS person-level scale, which is an FDA agreed-upon scale for evaluation of systemic agents in diabetic retinopathy. The inclusion criteria and scale used in this post-hoc analysis will be used in future APX3330 Phase 3 studies

Results : Results of the primary endpoint were presented at ARVO last year (Su et al, 2023; IOVS 64(8):3753). A post-hoc analysis of 68 subjects with 2 qualified eyes demonstrated a numerical reduction from baseline in binocular ≥ 3 step worsening on a DRSS person-level scale (a registration endpoint) at week 24, with 15.2% of placebo subjects worsening compared to 5.7% of APX3330 subjects (p=0.26) and a numerical reduction of binocular ≥ 4 step worsening, with 15.2% of placebo subjects compared to 0% of APX3330 subjects (p=0.07). This represents a 61% reduction in binocular ≥ 3 step worsening and 100% reduction in ≥ 4 step worsening between the placebo and APX3330 treated groups.

Conclusions : A clinically meaningful reduction in binocular ≥ 3 step and ≥ 4 step worsening in APX3330 treated subjects compared to placebo was observed in this trial. APX3330 may represent a promising oral treatment option for delaying or preventing disease progression in NPDR patients who otherwise are monitored and untreated until they progress to sight-threatening disease. These Phase 2 data support further evaluation of APX3330 in Phase 3 registration trials.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.