Last patient completes final visit in Ocuphire Pharma’s ZETA-1 Phase 2b 24-Week trial of APX3330

Oral ZPX3330 found to demonstrate favorable safety and tolerability profile in interim masked safety results, consistent with 11 Prior Trials of APX3330.

Ocuphire Pharma, Inc. this week announced that the last patient of the 103 enrolled subjects since April 2021 has completed their 24-week study visit in the Phase 2b ZETA-1 trial of oral APX3330 for the treatment of diabetic retinopathy (DR). Top-line results are expected in the fourth quarter of 2022.

In a statement, Mina Sooch, Ocuphire Pharma’s founder and CEO, noted that APX3330 is a potential first-in-class oral treatment for diabetic retinopathy/diabetic macular edema, where the need for early intervention remains high.

“With the final patient visit completed in this longer term study, we remain on track to report top-line results in the fourth quarter of this year, potentially bringing us one step closer to delivering the first small molecule, dual action, oral treatment option to patients with progressive vision-threatening diabetic eye disease,” Sooch said in a statement. “We look forward to sharing our top-line results later this year. In advance of the top-line results, Ocuphire plans to host a retina KOL webinar to showcase APX3330 and discuss the opportunity in DR.”

Sooch noted that the event is scheduled for October 14, 2022.

David Boyer, MD, senior partner, Retina-Vitreous Associates Medical Group said, “As an investigator in the ZETA-1 trial and a retina specialist that provides care for a large diabetic patient population, I am excited by the prospect of providing my DR/DME patients with a potential first-in-class, oral therapy with a novel dual mechanism of action of anti-inflammatory and anti-VEGF. Interim masked safety results seen to-date demonstrate favorable safety and tolerability profile, consistent with 11 prior trials of APX3330. If approved, APX3330 could represent a paradigm shift from observation and monitoring progression today to an early, non-injection treatment option.”

The multi-center, randomized, double-masked, placebo-controlled Phase 2b ZETA-1 trial was designed to evaluate the efficacy and safety of APX3330 in diabetic retinopathy patients. The study was conducted at 25 U.S. sites and enrolled 103 subjects with moderately severe to severe non-proliferative DR (NPDR) or mild proliferative diabetic retinopathy (mild PDR). Patients were randomized to receive 600 mg APX3330 or placebo daily over 24 weeks. The trial initiated in April 2021 and completed last patient last visit in August 2022.

According to the company, APX3330 is a first-in-class, small molecule, oral inhibitor of the transcription factor regulator Ref-1 (reduction-oxidation effector factor-1). With a novel dual mechanism of action, APX3330 blocks the downstream pathways regulated by Ref-1 -- including those involving angiogenesis (VEGF) and inflammation (NFkB) -- to decrease abnormal activation of both angiogenesis, and of inflammatory pathways that are implicated across several ocular diseases, including DR, DME, and age-related macular degeneration (AMD).

APX3330 has shown a favorable safety and tolerability profile over 11 clinical trials conducted in healthy, hepatitis, and cancer subjects prior to the current Phase 2 ZETA-1 trial in diabetic retinopathy.

The most recent interim analysis of masked safety data from ZETA-1 trial was presented by Michael Allingham, MD, PhD, at the American Society of Retina Specialists’ 40th Annual Scientific Meeting in July.

These data indicated that oral APX3330 continued to demonstrate a favorable safety profile consistent with the prior trials comprising hundreds of patients. Across all the trials, the safety findings represent over 9000 subject-days of exposure at the target dose of 600 mg/day.