Anti-PDGF inhibitor development continues despite negative results
Despite the failure of 2 clinical trials involving a combination therapy of platelet-derived growth factor (PDGF) inhibitor and anti-vascular endothelial growth factor (anti-VEGF) therapy, a third phase III study continues.
Reviewed by Pravin U. Dugel, MD
Despite the failure of 2 clinical trials involving a combination therapy of platelet-derived growth factor (PDGF) inhibitor and anti-vascular endothelial growth factor (anti-VEGF) therapy, a third phase III study continues.
Two phase III clinical trials designed to investigate the superiority of combination therapy with PDGF inhibitor E10030 (Fovista, Ophthotech) plus ranibizumab (Lucentis, Genentech) for improving visual acuity in eyes with neovascular age-related macular degeneration (nAMD) reportedly failed to meet their primary endpoint at 1 year.
The studies, which had a planned duration of 2 years, were terminated. However, a third phase III study investigating the potential benefit of adding the PDGF inhibitor to other anti-VEGF agents is ongoing, said Pravin U. Dugel, MD.
Dr. Dugel reviewed the rationale for the combination regimen as treatment for nAMD and topline results from preclinical and clinical trials. Dr. Dugel is managing partner, Retinal Consultants of Arizona, Phoenix, and clinical professor of ophthalmology, USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles.
“There is no doubt that anti-VEGF monotherapy has revolutionized treatment for nAMD, but there is also no doubt that it has significant limitations,” Dr. Dugel outlined. “About 75% of patients do not achieve significant improvement in vision, about 50% do not achieve driving vision of 20/40 or better, and after 2 years of treatment, about 25% of patients continue to lose vision.
“The biggest limitation, however, is the disconnect between visual acuity outcomes in clinical trials and those achieved in real-world practice,” said Dr. Dugel. “Simultaneous inhibition of VEGF and alternative pathways causing pathologic angiogenesis is a logical strategy for overcoming the limitations of anti-VEGF therapy and is the rationale for investigating the role of dual inhibition of PDGF and VEGF-A.”
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