Abstract
Purpose: :
XV-615 is a proprietary formulation of a novel low molecular weight vascular endothelial growth factor receptor 2 (VEGFR2) and platelet-derived growth factor (PDGFR) inhibitor. When dosed orally in rat CNV models, the drug substance potently inhibits angiogenesis (Huang D, et al. IOVS 2009;50: E-Abstract 2966). The present study focuses on safety assessment of XV-615 delivered to rabbits by intravitreal injection.
Methods: :
Three groups of New Zealand white rabbits (N = 3) received intravitreal injections (50 µL) of either 500 µg XV-615, 50 µg XV-615, or vehicle. Animals were observed for 30 days, during which period ocular exams, intraocular pressure measurements, and electroretinograms were performed. At the end of the study, animals were euthanized and eyes were processed for histology.
Results: :
Intravitreal injection of XV-615 was well tolerated in all groups. Slight conjunctival congestion was observed 24 hours post injection in some animals that received either 500 µg or 50 µg XV-615. There was no evidence of ocular inflammation or congestion in any animals 48 hours post injection. Immediately after injection, XV-615 was visible in the vitreous cavity in the high and low dose groups, and its presence declined steadily over the course of the experiment. At the end of the 30 day study period, trace amounts of XV-615 were still visible in the inferior vitreous in the high dose group but not low dose group. Intraocular pressure remained normal throughout the study. All retinal exams were devoid of any findings, and electroretinograms on Day 14 were normal. Histologic analysis did not reveal evidence of ocular toxicity associated with XV-615.
Conclusions: :
Intravitreal delivery of XV-615 was well tolerated in rabbits over a 30 day period. No evidence of toxicity was observed in doses up to 500 µg per eye. Confirmatory studies in additional species may be required to further evaluate the safety of intravitreally injected XV-615.
Keywords: age-related macular degeneration • retinal neovascularization • drug toxicity/drug effects