Ocuphire Pharma Announces End-of-Phase 2 Meeting with FDA for Oral APX3330 in Diabetic Retinopathy

Ocuphire Pharma announced the successful outcome of an end-of-phase 2 (EOP2) meeting with the FDA supporting the advancement of oral APX3330 for the treatment of diabetic retinopathy (DR) into phase 3 studies based on the recently completed phase 2 ZETA-1 trial.

“We are pleased to have FDA agreement on the primary endpoint for phase 3 pivotal trials of APX3330 which we believe is the most advanced oral therapy currently in development for diabetic retinopathy,” George Magrath, MD, MBA., MS, Chief Executive Officer of Ocuphire, said in a company news release. “Results from our phase 2 ZETA-1 results demonstrate that oral APX3330 has the potential to slow or prevent clinically meaningful progression of diabetic retinopathy, as measured by the percentage of subjects with ≥ 3-step worsening on a binocular diabetic retinopathy severity scale (DRSS), which will be the phase 3 primary endpoint. As recommended by the FDA, Ocuphire plans to submit a Special Protocol Assessment to agree on the clinical trial protocol and statistical analysis plan for the phase 3 trials and will share specifics on the study design parameters and anticipated timing once agreed with the FDA. We are grateful for the FDA’s support and guidance and look forward to continued collaboration as we advance APX3330 into phase 3 development.”

The EOP2 meeting was supported by results from the previously completed phase 2 ZETA-1 trial. The randomized, double-masked, placebo-controlled phase 2 trial was designed to evaluate the efficacy and safety of oral APX3330 in diabetic retinopathy patients. A higher percentage of placebo-treated patients had ≥ 3-step worsening on binocular DRSS from baseline compared to APX3330-treated patients at 24 weeks. APX3330 demonstrated favorable safety and tolerability in diabetic patients.

“Given the increasing number of DR patients and current treatment options, I am encouraged by the results of the ZETA-1 trial showing that APX3330 can potentially slow or prevent progression to vision threatening diseases such as proliferative diabetic retinopathy," David Brown, MD, FACS, co-chairman of the medical leadership board at Retina Consultants of America (RCA), said in the news release. "The current treatment paradigm for NPDR patients is for physicians to monitor progression every 4-6 months depending on DR severity. Approved anti-VEGF therapies are not widely utilized in NPDR patients because of the necessity for consistent intravitreal injections in asymptomatic patients. A safe convenient oral medication that could slow or prevent diabetic retinopathy would be a major advance in our fight against diabetic blindness.”

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 – which involve angiogenesis (VEGF) and inflammation (NFkB) – 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). APX3330 has shown a favorable safety and tolerability profile in 12 clinical trials conducted in healthy, hepatitis, cancer, and diabetic subjects.