Successful phase 1B study of oral therapy for diabetic retinopathy

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Breye Therapeutics announced the successful completion of its phase 1b clinical trial of an oral therapy, danegaptide, for early treatment of non-proliferative diabetic retinopathy (NPDR) and associated edema.

Danegaptide is a first-in-class oral small molecule with a novel mode of action that stabilizes the vasculature and protects against cell-cell uncoupling, retinal capillary breakdown, and vascular leakage caused by hyperglycemia, according to the company.

The drug has the potential to fill a treatment gap for these patients. 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, according to the press release.

Phase 1 trial

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 performed in 11 clinical sites in the UK, Germany, and the US and enrolled 24 patients.

According to a company press release, the first-in-class oral treatment demonstrated that

• The oral treatment was well tolerated, with early signs of clinical activity
• In models of NPDR, danegaptide has demonstrated protection against retinal capillary loss and vascular leakage
• Data support continued advancement into Phase 2 clinical evaluation

No dose-limiting toxicities were reported. The 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 observed.

“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.

“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. Additionally, we believe this treatment solution may also support the maintenance of treatment response after induction therapy with intravitreally administered products,” according to Ulrik Mouritzen, Chief Executive Officer of Breye Therapeutics.

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.