Breye Therapeutics has completed a phase Ib clinical trial evaluating danegaptide, an oral therapy for non-proliferative diabetic retinopathy with associated edema, a diabetes-related eye condition where damaged retinal blood vessels leak fluid, causing swelling (edema) in the macula. This can blur vision and lead to blindness if untreated.
The trial demonstrated that oral danegaptide was well tolerated across all dose levels, with no dose-limiting toxicities reported. Pharmacokinetic data confirmed that targeted exposures were achieved, and early signs of clinical activity were observed through retinal imaging, indicating reductions in vascular leakage and improvements in anatomical parameters.
Danegaptide works by stabilizing the vasculature and protecting against retinal capillary breakdown and vascular leakage caused by hyperglycemia. According to the company, it offers a non-invasive treatment solution, which can be used at an earlier disease stage, compared to late-stage disease where the current intravitreal treatments are used.
“Intravitreally administered products, injected directly into the eye for patients with late-stage diabetic retinopathy, have prevented patients from going blind. However, such injections are invasive and burdensome. We wanted to develop a non-invasive medication that can treat both eyes and halt and reverse the core disease pathologies,” says Breye CEO Ulrik Mouritzen.
Treatment options for diabetic retinopathy are currently limited for patients in the earlier or moderate stages of the disease. Ideally patients should be treated at earlier stages to prevent irreversible tissue damage and the need for needle-based therapies. The intravitreal treatments are known to be poorly tolerated and associated with low compliance, highlighting the critical need for alternative solutions.
While danegaptide was previously being evaluated as a treatment for different cardiac conditions, Mouritzen explains that the therapeutic indication of diabetic retinopathy provided an opportunity to treat where there is ample time to intervene as the disease is slowly progressive.
Mouritzen adds, “As an oral and non-invasive therapy, danegaptide can treat patients with moderate to severe NPDR, who otherwise have limited treatment options as the currently approved needle-injections are too burdensome for patients to accept, highlighting the critical need for more effective and non-invasive treatment solutions. Roughly half of patients become non-compliant to the needle-based therapies after a year.”
All treatment guidelines for diabetes state that patients should have their eyes checked at least once a year due to the slow progression and “silent” nature of non-proliferative diabetic retinopathy. Non-invasive retinal imaging and AI can help find more patients at risk, and initiate treatment earlier. The treatment goal of orally administered danegaptide is to halt and reverse the disease and thereby bring the patients into a lower disease score with reduced risks for developing vision threatening events. Patients would take the orally administered medication together with their orally administered anti-diabetic medications.
“A subsequent phase II trial is planned to evaluate danegaptide in a targeted patient population using the regulatory endpoint of ≥2-step improvement on the Diabetic Retinopathy Severity Scale (DRSS), which classifies retinopathy from none to mild, moderate, and severe non-proliferative, and proliferative diabetic retinopathy,” says Mouritzen. “We are actively fundraising to support this next phase of development. Our focus is on validating the findings. In our phase III plans, we have included a clinical trial designed to generate data evaluating danegaptide as a maintenance therapy after six months of IVT-based induction therapy in patients with advanced disease.”
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