Phase 2 clinical trial kicks off for diabetic retinopathy drug candidate

Ocuphire Pharma Inc. announced this week it is screening the first patients in ZETA-1 (NCT04692688), a Phase 2 trial to evaluate APX3330 in non-proliferative diabetic retinopathy (NPDR) and mild proliferative diabetic retinopathy (mild PDR).

According to the company, the effects on diabetic macular edema will be explored as a secondary outcome. A number of retinal centers across the US are active and recruiting eligible diabetic retinopathy patients.

The ZETA-1 trial is a randomly assigned, placebo-controlled, double-masked study designed to evaluate the efficacy of APX3330 to improve diabetic retinopathy over 24 weeks. The study will be conducted in up to 20 U.S. sites and is expected to enroll approximately 100 subjects with moderately-severe to severe NPDR or mild PDR in the study eye. 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.

The primary endpoint of the study will evaluate the percentage of subjects with a ≥ 2 step improvement on the Diabetic Retinopathy Severity Scale (DRSS) score. Secondary endpoints include evaluation of central subfield thickness to assess effects on diabetic macular edema, BCVA, safety and tolerability.

The company noted that ZETA-1 is investigating the potential of APX3330 to offer an oral treatment for diabetic retinopathy that addresses both of these disease pathways.

“There remains a strong need to develop a non-injectable alternative treatment option for patients with DR as these injectables—although approved for this indication— are not widely used,” Peter K. Kaiser, MD, a professor of ophthalmology at the Cole Eye Institute of the Cleveland Clinic Foundation, said in a statement. “If successfully developed, APX3330 could lead to the first oral option for DR as well as an adjunct therapy that may improve dosing convenience and compliance by alleviating some of the burden of chronic anti-VEGF injection treatments for DME and other retinal diseases.”

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

Mark R. Kelley, PhD, a professor in the Department of Pediatrics and Glick Eye Center at Indiana University School of Medicine, co-founder of the APX3330 program, and a member of Ocuphire’s Medical Advisory Board, noted that it is rewarding to see APX3330 begin the Phase 2 trial in ophthalmology with the potential to offer a new treatment option for patients with retinal diseases, particularly diabetics.

“APX3330, a potential first oral therapy for DR, is not only novel in its oral route of administration, but it builds on decades of studies targeting Ref-1 as an impactful way to block both angiogenesis and inflammation using a single drug candidate,” he said in a statement.

Diabetes remains the leading cause of blindness among adults from 20 to 74. In the United States alone, more than 7 million patients suffer from diabetic retinopathy (DR), a complication of diabetes in which chronically elevated blood sugar levels cause damage to blood vessels in the retina. Moreover, an additional 750,000 patients suffer from diabetic macular edema (DME), one of the most common complications of diabetic retinopathy where the macula swells from fluid leaked from damaged blood vessels. The disease progression of both DR and DME involves abnormal vessel proliferation and inflammation.

Current approved treatments for DR and DME encompass a more than $10 billion global market and involve administering anti-VEGF injections to decrease vessel formation or steroids to decrease inflammation into eyes with advanced retinal disease.

Mina Sooch, president and CEO of Ocuphire Pharma, noted that the company is looking forward to the -1 Phase 2 clinical trial.

“Building off of 11 prior trials that have demonstrated a favorable safety and tolerability profile in over 300 oncology and hepatic patients, APX3330 has the potential to become the first oral therapy used for diabetic retinopathy,” Sooch said in a statement. “Due to its highly differentiated mechanism of action, we believe that APX3330 could also emerge as an important add-on therapy with the currently approved anti-VEGF treatments and extend the time between injections. The team at Ocuphire has now initiated all 4 clinical trials planned since its public listing last November, and we look forward to continuing enrollment and data readouts over the next 12 months.”