Ocuphire Pharma, Inc. announced topline efficacy and safety results from its ZETA-1 Phase 2 trial evaluating oral APX3330 for the treatment of diabetic retinopathy. ZETA-1 was a randomized, double-masked, placebo-controlled Phase 2 trial designed to evaluate the efficacy and safety of APX3330 in diabetic retinopathy patients. ZETA-1 was conducted at 25 U.S. sites and enrolled 103 patients with at least one eye meeting criteria for moderately severe to severe non-proliferative DR or mild proliferative diabetic retinopathy.

The ETDRS diabetic retinopathy severity scale is a categorical tool for clinical trials that contains 10 discreet steps, from no retinopathy to severe proliferative retinopathy, derived from the grading of fundus photographs for each eye at a central reading center. Each patient's study eye had a baseline DRSS step of 5, 6 or 7. The patients were randomized to receive 600 mg APX3330 or placebo daily over 24 weeks. Primary and secondary endpoints evaluated +/- 1, 2, 3, and 4 step improvement and worsening in DRSS at week 12 and week 24, change in best-corrected visual acuity change in central subfield thickness and safety and tolerability.

Patient demographics and baseline characteristics were well-balanced across both treatment groups. In the ZETA-1 Phase 2 trial, APX3330 did not meet the primary endpoint Given the oral systemic delivery of APX3330, however, it is important to evaluate the effect on both eyes. A potential Phase 3 registration primary endpoint is a = 3-step worsening of DRSS as a composite of both eyes.

This secondary endpoint was pre-specified and evaluated in the ZETA-1 trial. APX3330 demonstrated statistically significant reduction of disease progression at 24 weeks: No (0%) APX3330-treated patients had a binocular = 3-step worsening of DRSS from baseline compared with 16% for placebo-treated patients. This endpoint is the planned Phase 3 primary endpoint for future registration trials that will be confirmed at the EOP2 meeting with the FDA.

Additional efficacy endpoints were directionally favorable to support the effect of APX3330 in slowing the progression of DR and preserving vision. Visual acuity was stable with APX3330 and a trend was seen with fewer APX3330 treated patients losing 5 or more letters of distance vision compared to placebo patients. APX3330 showed a favorable safety and tolerability profile.

Treatment-related adverse events were uncommon, and most were mild in severity. There were no treatment-related serious adverse events. No changes were observed in liver, kidney, or heart function as well as complete blood count and comprehensive metabolic panel.

Further analysis of the trial data is ongoing and detailed results will be presented at multiple medical meetings and submitted for peer review publication in 2023, including Angiogenesis, Exudation and Degeneration, February 10-11, 2023, and The Macula Society Annual Meeting, February 15–18, 2023.