Researchers from AsclepiX Therapeutics and the Johns Hopkins University School of Medicine have evaluated a new suprachoroidal formulation of AXT107, an anti-angiogenic peptide for retinal and choroidal vascular diseases, designed to deliver sustained activity from a single injection. The 9-month GLP toxicology study in Göttingen minipigs supporting the safety of this approach was conducted at Versa Biomedical’s facilities in Barcelona (then Specipig). Download case

About the study:

Purpose

Retinal and choroidal vascular diseases, such as neovascular age-related macular degeneration and diabetic macular oedema, are leading causes of vision loss, and current treatments require frequent intravitreal injections. The study set out to assess whether AXT107, reformulated as microparticles and delivered into the suprachoroidal space, could provide sustained anti-angiogenic activity with a favourable ocular safety profile.

Methods

Safety and durability were evaluated in a 9-month GLP toxicology study at Versa Biomedical. Thirty-two Göttingen minipigs were randomised into four groups and received a single suprachoroidal injection in both eyes, using microneedles: vehicle, or 0.125, 0.5 or 1.25 mg of AXT107 per eye. Intraocular pressure, ocular health and systemic exposure were monitored throughout the study. At the end of the study, AXT107 levels were measured in the ocular tissues.

Results

In previous rats studies, the microparticle formulation reduced neovascular area by approximately 60% compared with vehicle. In minipigs, OCT imaging confirmed successful delivery to the suprachoroidal space. Intraocular pressure rose briefly after injection and had returned to normal by the first follow-up at one week. Mild ocular findings resolved by day 5. No treatment-related adverse findings were observed for the rest of the study. Nine months after a single injection, AXT107 was still present in the choroid/RPE and sclera, and it was not detected in blood at any time point.

Conclusions

Suprachoroidal delivery of AXT107 microparticles showed sustained activity, prolonged tissue retention and a favourable ocular safety profile. The highest dose tested, 1.25 mg per eye, was established as the no-observed-adverse-effect level. These results support further clinical development, and the programme has since advanced into clinical evaluation.

Keywords

Ophthalmology; Retinal vascular diseases; Suprachoroidal delivery; Microparticles; GLP toxicology; Göttingen minipig.