Abstract
Purpose :
The administration of anti-vascular endothelial growth factor (VEGF) agents has become a first-line treatment for neovascular Age-Related Macular Degeneration (nAMD). However, persistent fluid and active exudation is common following anti-VEGF therapy. Beyond VEGF, fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) were shown to play a role in the signaling cascade for angiogenesis that is related to the pathophysiology of nAMD. Developing a therapy that can inhibit VEGF, FGF and PDGF pathways may improve treatment efficacy while decreasing the occurrence rate of drug resistance.
AIV007 is a potent, broad-spectrum kinase inhibitor of VEGF, FGF, and PDGF receptors currently in clinical development. Its effect on neovascularization, granulomatous inflammation, and subretinal fibrosis were evaluated in multiple ocular pharmacology animal models.
Methods :
AIV007, vehicle, and/or anti-VEGF antibody administered by intravitreal injection or eyedrop were evaluated in the following animal models:
- Laser-induced choroidal neovascularization (CNV) in rats
- Suture-induced corneal neovascularization and fibrosis in rabbits
- Scar formation and fibrosis following glaucoma filtration surgery in rabbits
- CNV and subretinal fibrosis in mice
Results :
AIV007 treatment, as compared to vehicle, significantly reduced lesion size by 44.5% in the CNV rat model and showed inhibition of corneal neovascularization by 94.7% in the rabbit corneal neovascularization and fibrosis model. In the rabbit glaucoma model, AIV007 reduced neovascularization by 47.6% and collagen density and distribution by 33.3% following trabeculectomy surgery. In a mouse model, AIV007 inhibited CNV leakage by 83.6% with a 43.7% reduction in subretinal fibrosis. Taken together, the significant findings in these ocular animal models supported the advancement of AIV007 to the clinic.
Conclusions :
AIV007 demonstrated significant inhibition of neovascularization and granulomatous inflammation, and reduction of subretinal fibrosis in multiple ocular pharmacology animal models. These findings support the clinical development of AIV007 for retinal diseases associated with these clinical symptoms such as edema and fibrosis. AIV007’s broad spectrum inhibition of VEGF, FGF and PDGF pathways may offer therapeutic benefits over current anti-VEGF agents.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.