Breye Therapeutics has announced the successful completion of its Phase 1b clinical trial evaluating danegaptide, an oral therapy for the early treatment of non-proliferative diabetic retinopathy (NPDR) and associated edema. The first-in-class oral small molecule represents a potential breakthrough in addressing a significant treatment gap for patients with early-to-moderate stage diabetic eye disease.
Novel Mechanism Targets Vascular Stabilization
Danegaptide operates through a novel mode of action that stabilizes the vasculature and protects against cell-cell uncoupling, retinal capillary breakdown, and vascular leakage caused by hyperglycemia. This mechanism addresses the underlying pathophysiology of diabetic retinopathy at its early stages, potentially preventing progression to more severe forms of the disease.
The drug has the potential to fill a critical treatment gap for patients with NPDR. While successful intravitreally administered products have been developed for patients with late-stage disease, treatment options are currently limited for patients in the earlier or moderate stages. The intravitreal treatments are burdensome, often poorly tolerated, and associated with low compliance, highlighting the critical need for effective and non-invasive alternatives.
Phase 1b Trial Design and Results
The Phase 1b trial was a multicenter, open-label, dose-escalation study that assessed the safety, tolerability, pharmacokinetics, and early signs of biologic activity of danegaptide in patients with NPDR and associated diabetic macular edema. The study was conducted across 11 clinical sites in the UK, Germany, and the US, enrolling 24 patients.
The trial demonstrated several key findings:
- The oral treatment was well tolerated, with early signs of clinical activity
- No dose-limiting toxicities were reported
- Pharmacokinetic data confirmed that targeted exposures of danegaptide were reached as guided by preclinical data
- Early signs of clinical activity were observed on retinal imaging, with reductions in retinal vascular leakage and improvements in anatomic parameters
In preclinical models of NPDR, danegaptide has demonstrated protection against retinal capillary loss and vascular leakage, supporting its therapeutic potential.
Clinical Expert Perspectives
"An oral approach like danegaptide has the potential to fundamentally shift how we treat moderate-to-severe stages of diabetic eye disease, offering patients a much-needed and non-invasive treatment solution for the large group of patients with NPDR," said Carl Regillo, MD, Director of Retina Service of Wills Eye Hospital, Professor of Ophthalmology at Thomas Jefferson University in Philadelphia, and a member of the Breye Therapeutics Scientific Advisory Board.
Path Forward to Phase 2
Ulrik Mouritzen, Chief Executive Officer of Breye Therapeutics, emphasized the significance of these results: "These results continue to support danegaptide's potential as an oral, non-invasive therapeutic solution for patients in the earlier stages of diabetic retinopathy. As we now prepare to advance into Phase 2 clinical evaluation, our focus is on validating these findings using regulatory-accepted clinical outcomes to progress our mission of developing safe and effective treatment options for these patients to preserve their vision before the onset of irreversible damage."
The company also believes this treatment solution may support the maintenance of treatment response after induction therapy with intravitreally administered products, potentially offering a combination approach for comprehensive diabetic retinopathy management.
A subsequent Phase 2 trial is planned to evaluate danegaptide in a targeted NPDR patient population using the regulatory endpoint of ≥2-step improvement on the Diabetic Retinopathy Severity Scale, a well-established measure for assessing therapeutic efficacy in diabetic retinopathy trials.
