Danegaptide Shows Promise in Reducing Diabetic Retinopathy Leakage | Healio

A new oral therapy, danegaptide, is showing promise in the early treatment of nonproliferative diabetic retinopathy (NPDR), a leading cause of vision loss. Results from a phase 1b clinical trial, presented at the Angiogenesis, Exudation, and Degeneration 2026 meeting, suggest that the drug may reduce vascular leakage and macular exudation in some patients.

Diabetic retinopathy develops as a complication of diabetes, damaging the blood vessels in the retina. NPDR is an early stage of the disease, characterized by changes in retinal blood vessels but without the growth of new, fragile vessels. While treatments exist for more advanced stages, options for early intervention have been limited, often requiring frequent and burdensome intravitreal injections.

Danegaptide, developed by Breye Therapeutics, is a first-in-class oral small molecule designed to stabilize the vasculature and protect against retinal capillary breakdown and vascular leakage caused by hyperglycemia – high blood sugar. The phase 1b trial, conducted across 11 clinical sites in the U.K., Germany, and the U.S., involved 24 adults with NPDR and associated diabetic macular edema. Participants received oral danegaptide once or twice daily for 28 days, followed by 14 days of follow-up.

The study focused on assessing the safety, tolerability, and pharmacokinetics of danegaptide, as well as early signs of biological activity. Researchers found that the drug was well-tolerated, with no dose-limiting toxicities reported. Plasma levels of the drug were maintained within targeted ranges. Importantly, no clinical safety signals were observed during the trial period.

Analysis of the data revealed that in 55% of patients, there were signs of reduced vascular leakage – indicated by decreased area and intensity of fluorescein leakage – and/or reduced macular exudation, evidenced by decreased macular thickness, macular volume, and fewer intraretinal cysts. These findings were assessed using fluorescein angiography and high-definition optical coherence tomography (OCT).

“Danegaptide has the potential to be a medicine capable of treating diabetic retinopathy from its earlier [nonproliferative diabetic retinopathy] stages,” said Carl D. Regillo, MD, director of the retina service at Wills Eye Hospital and a member of Breye’s scientific advisory board, in a press release. “This would create new options for how diabetic retinopathy is treated — opening the door to halting or even reversing disease and treating it before the risk emerges of disease progression to advanced forms.”

The successful completion of the phase 1b trial, initially announced in June 2025, has paved the way for a phase 2 randomized clinical trial. Breye Therapeutics is currently fundraising to support this next stage of research.

This development offers a potential new avenue for managing diabetic retinopathy, particularly for patients in the early stages of the disease. The oral administration of danegaptide could offer a significant advantage over current treatments, which often require invasive intravitreal injections. However, it’s important to remember that these are early-stage trial results, and further research is needed to confirm the efficacy and long-term safety of danegaptide.

The need for more accessible and less invasive treatments for diabetic retinopathy is significant. Diabetic retinopathy affects millions worldwide, and early detection and intervention are crucial for preventing vision loss. The potential of an oral therapy like danegaptide to address this unmet need is a promising development in the field of retinal disease.