Biochemical Basis and Therapeutic Implications of Angiogenesis by Jawahar L. Mehta Pankaj Mathur & Naranjan S. Dhalla

Author:Jawahar L. Mehta, Pankaj Mathur & Naranjan S. Dhalla
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

7.1.2 Novel/Experimental Agents

Anti-platelet Derived Growth Factor (PDGF)

Pericytes play an important role in the maintenance of neovascular endothelial cells by secreting VEGF and other growth factors. Fovista (Ophthotech, New York, NY) is a 32-mer pegylated DNA aptamer that selectively binds to PDGF-BB and PDGF-AB receptors on pericytes. In addition, inhibition of PDGF can reduce the recruitment of non-neovascular components such as myofibroblasts, RPE, and glial cells around the neovascular endothelial cells to limit the amount of fibrovascular and fibrous tissues. In combination with an anti-VEGF agent, Fovista enhances the anti-angiogenic effect by stripping pericytes from neovascular endothelial cells. In the multi-centered randomized control phase IIb trial, combination therapy of fovista and ranibizumab achieved a 62% incremental benefit in terms of visual outcome compared to ranibizumab alone in patients with subfoveal classic CNV. The combination therapy group also had less severe subretinal fibrosis, as well as less progression of subretinal fibrosis compared to the ranibizumab monotherapy group [77]. Unfortunately, the phase III trials failed to demonstrate superiority of fovista combination therapy over ranibizumab monotherapy.

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