Ocuphire Completes Enrollment in 24-Week ZETA-1 Phase 2b Trial of Oral APX3330 for the Treatment of Diabetic Retinopathy

Ocuphire Pharma announced that it has completed enrollment of 103 diabetic patients with moderately severe-to-severe nonproliferative diabetic retinopathy (NPDR) or mild proliferative diabetic retinopathy (mild PDR) in ZETA-1, a phase 2b trial evaluating the efficacy and safety of APX3330 for the treatment of diabetic retinopathy (DR) at 25 investigational sites across the US in less than a year.

Currently approved treatments for DR consist mainly of anti-VEGF injections to improve retinal vascular integrity. Despite their approval for the treatment of DR, intravitreal injection therapies are not widely used in patients at an early stage without macular edema or proliferative diseases because of the asymptomatic nature before progression and patients’ resistance to adhere to invasive and frequent VEGF therapies.

“APX3330 is a potential first oral therapy for DR/DME. It has a highly differentiated dual mechanism of action supported by an extensive body of evidence suggesting that targeting Ref-1 can block both angiogenesis and inflammation,” David Boyer, MD, practicing ophthalmologist at Retina-Vitreous Associates Medical Group, Medical Adviser to Ocuphire, and Investigator in the ZETA-1 trial, said in a company news release. “If approved, APX3330 as an oral, systemic therapy has the potential to address the large unmet need in diabetic retinopathy patients and other diabetes-related complications such as diabetic nephropathy and neuropathy. Importantly, it could also be used as an oral adjunct therapy in patients with PDR or DME that may improve dosing convenience and compliance by alleviating the burden associated with chronic anti-VEGF intravitreal injection treatments.”

The ZETA-1 trial is a multicenter, randomized, placebo-controlled, double-masked phase 2b trial designed to evaluate the safety and efficacy of APX3330 in DR. A total of 103 subjects (target of 80-100) with moderately severe-to-severe NPDR or mild PDR with a Diabetic Retinopathy Severity Scale (DRSS) score between 47 and 61 have been enrolled. Subjects are randomized to receive 600mg APX3300 or placebo daily over 24 weeks. The primary endpoint is a responder analysis that evaluates the percentage of subjects with a ≥ 2 step improvement on the DRSS score. If patients who are enrolled also have DME in their non-study eye, this eye will also be followed during the trial for potential improvement. Secondary endpoints include evaluation of central subfield thickness to assess effects on diabetic macular edema, BCVA, safety, and tolerability. For more information about the ZETA-1 phase 2b trial design and its US clinical sites, refer to www.ClinicalTrials.gov Identifier: NCT04692688.

Jeffrey Heier, MD, Medical Advisor to Ocuphire added, “As an investigator in many retinal clinical trials, historically, we have faced challenges with patient enrollment and retention. This trial enrolled remarkably well, and we would like to thank the ZETA-1 investigators, their site staff, and especially the patients electing to participate in a 6-month trial with multiple site visits during a global pandemic. It speaks to the unmet need and patient willingness to adopt and continue self-administering a convenient oral treatment option. An oral treatment has the potential to minimize the need for frequent office visits and intraocular injections, thereby making treatment more accessible to patients for whom such visits are difficult, including those in rural areas in the U.S. and globally.”

Mina Sooch, MBA, CEO and Founder, Ocuphire Pharma commented, “Completion of enrollment in ZETA-1 in under a year is impressive relative to competitive DR trials over the last few years. In addition, this trial marks the completion of enrollment of four late-stage clinical trials in the first few months of 2022. We are very pleased to have exceeded enrollment with more than 100 DR patients in ZETA-1 Phase 2b trial and we look forward to the 24-week primary endpoint data in the second half of 2022. The team at Ocuphire is excited to be advancing APX3330 as the first small molecule, dual action, oral treatment option with the potential to address the high unmet need for early intervention for progressive vision-threatening diabetic eye disease.”