Dual VEGF and PDGF Antagonists to Treat Exudative AMD
Dual VEGF and PDGF Antagonists to Treat Exudative AMD
Neovascular AMD is a major cause of visual disability worldwide, yet current treatment strategies have substantial limitations. Advancements in vascular biology, in part fueled by cancer research, led to the development and the US FDA approval of the first pharmacotherapies for wet AMD: pegaptanib, ranibizumab and recently aflibercept. Although the development of VEGF inhibitors for wet AMD has been a major therapeutic advancement, work in oncology and vascular biology indicates that combined inhibition of VEGF and PDGF in wet AMD may be more effective than VEGF inhibition alone. VEGF stimulates early vessel growth while PDGF stabilizes maturing vessels by recruiting pericytes to the vascular endothelium. Hence, dual inhibition offers the opportunity to target both immature and maturing vessels. Additionally, PDGF inhibition has the added theoretical benefit of reducing subretinal scarring that follows CNV regression. Such scarring limits the visual potential in AMD after stabilization of the CNV. Recent case studies with sorafenib and early-stage clinical trials with pazopanib (GSK) and E10030 (Ophthotech) suggest that combined VEGF/PDGF inhibition is more effective than anti-VEGF monotherapy. Although these early studies are promising, we hope to learn more about the potential for dual VEGF/PDGF inhibition for wet AMD as programs for pazopanib and E10030 advance into late-stage clinical trials.
Expert Commentary
Neovascular AMD is a major cause of visual disability worldwide, yet current treatment strategies have substantial limitations. Advancements in vascular biology, in part fueled by cancer research, led to the development and the US FDA approval of the first pharmacotherapies for wet AMD: pegaptanib, ranibizumab and recently aflibercept. Although the development of VEGF inhibitors for wet AMD has been a major therapeutic advancement, work in oncology and vascular biology indicates that combined inhibition of VEGF and PDGF in wet AMD may be more effective than VEGF inhibition alone. VEGF stimulates early vessel growth while PDGF stabilizes maturing vessels by recruiting pericytes to the vascular endothelium. Hence, dual inhibition offers the opportunity to target both immature and maturing vessels. Additionally, PDGF inhibition has the added theoretical benefit of reducing subretinal scarring that follows CNV regression. Such scarring limits the visual potential in AMD after stabilization of the CNV. Recent case studies with sorafenib and early-stage clinical trials with pazopanib (GSK) and E10030 (Ophthotech) suggest that combined VEGF/PDGF inhibition is more effective than anti-VEGF monotherapy. Although these early studies are promising, we hope to learn more about the potential for dual VEGF/PDGF inhibition for wet AMD as programs for pazopanib and E10030 advance into late-stage clinical trials.
