Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration

Background: Recent studies have suggested that vascular endothelial growth factor (VEGF) is an important stimulus for the growth of new blood vessels in the eye. Anti-VEGF therapy is thus a potential treatment for exudative macular degeneration and diabetic retinopathy. Methods: Previously described animal models of vascular leakage and ocular neovascularization, including the Miles assay, the rat corneal angiogenesis model, and the mouse retinopathy of prematurity (ROP) model, were used to study this drug. After these studies, a phase 1A single ascending dose study of intravitreal injections of the drug was performed in 15 patients with subfoveal choroidal neovascularization secondary to exudative age-related macular degeneration (AMD). Results: The Miles assay model showed almost complete attenuation of VEGF-mediated vascular leakage following addition of EYE001, and the corneal angiogenesis model also showed a significant reduction in neovascularization with EYE001. The ROP model showed inhibition of 80% of the retinal neovascularization compared with controls (P = 0.0001). The phase 1A safety study of patients with exudative AMD showed no significant safety issues related to the drug. Ophthalmic evaluation revealed that 80% of patients showed stable or improved vision 3 months after treatment and that 27% of eyes demonstrated a three-line or greater improvement in vision on the Early Treatment for Diabetic Retinopathy Study chart at this time. Conclusion: Anti-VEGF therapy is a promising new avenue for the treatment of neovascular diseases of the eye, including exudative macular degeneration and diabetic retinopathy. Preclinical data from studies with EYE001 support clinical evaluation of its efficacy in such diseases. This report is the first to describe administration of anti-VEGF therapy in humans for exudative macular degeneration and shows the safety of such therapy for single injections. Further clinical studies are necessary to determine the safety of multiple intravitreal injections of EYE001 and larger studies are needed to prove the efficacy of this novel, potentially therapeutic agent for neovascular AMD.