Opus Genetics, Inc. (Nasdaq: IRD) has secured a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA) for its Phase 3 clinical trial evaluating oral APX3330 in patients with moderate to severe non-proliferative diabetic retinopathy (NPDR). The SPA agreement indicates that the FDA finds the trial design, endpoints, and planned analyses adequate to support a New Drug Application (NDA) submission, contingent on the trial's success and a comprehensive review of all data.
The primary endpoint agreed upon with the FDA is a reduction in 3-step or greater worsening on the binocular diabetic retinopathy severity scale (DRSS) score compared to placebo. This agreement provides a clear regulatory pathway for APX3330, a first-in-class, small molecule, oral inhibitor of the transcription factor regulator Ref-1 (reduction-oxidation effector factor-1).
Clinical Significance of APX3330
APX3330's novel mechanism of action modulates downstream pathways regulated by Ref-1, impacting angiogenesis (VEGF), oxidative stress (Nrf2), and inflammation (NFkB). This multimodal approach aims to restore homeostatic levels of angiogenic, oxidative stress, and inflammatory factors implicated in various ocular diseases, including diabetic retinopathy (DR), diabetic macular edema (DME), and age-related macular degeneration (AMD).
In a previous Phase 2 ZETA-1 trial, oral APX3330 demonstrated the potential to slow or prevent clinically meaningful progression of DR and exhibited a favorable safety profile. The Phase 3 trial aims to confirm these findings and establish APX3330 as a transformative treatment option for patients with NPDR.
Management Perspective
"This SPA agreement reflects our alignment with the FDA on the design of a Phase 3 trial for APX3330 and is a testament to the team’s developmental and regulatory acumen," said George Magrath, M.D., Chief Executive Officer of Opus Genetics. "If successful in Phase 3 and subsequently approved, APX3330 has the potential to be a transformative treatment option for patients with NPDR. We believe that having this SPA in place will help de-risk certain regulatory aspects of this program. Our intention is to seek a partner for APX3330 to fund further development, as we focus our resources on advancing our gene therapy candidates for IRDs."
Diabetic Retinopathy: A Significant Unmet Need
Diabetic retinopathy is a progressive eye disease and a leading cause of blindness in working-age adults, affecting approximately 10 million patients in the US. The disease results in vision impairment and blindness among adults with diabetes, highlighting the urgent need for effective treatments.
About Opus Genetics
Opus Genetics is focused on developing gene therapies for inherited retinal diseases (IRDs) and small-molecule drugs for other ophthalmologic disorders. Their pipeline includes adeno-associated virus (AAV)-based gene therapies targeting mutations in genes causing bestrophinopathy, Leber congenital amaurosis (LCA), and retinitis pigmentosa. The company's lead gene therapy program targets mutations in the LCA5 gene and is currently in a Phase 1/2 trial. Additionally, Opus is developing Phentolamine Ophthalmic Solution 0.75% for presbyopia and reduced dim light vision following keratorefractive surgery.
