A phase I study of an intravitreal anti-platelet-derived growth factor (PDGF) aptamer (E10030, Ophthotech) that targets pericytes, evaluated in combination therapy with ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (AMD), indicated that the drug is safe and seems to have biologic activity against choroidal neovascularization (CNV), said David Boyer, MD, of Retina-Vitreous Associates, Beverly Hills. 

“Ranibizumab is the gold standard and has provided great benefit to patients, but despite improvements in vision, CNV still grows, as seen in several trials,” added Dr. Boyer, speaking for the Ophthotech Study Group. “We may be able to improve vision by reducing the size of the CNV.” 

The hallmark of maturation is the presence of pericytes. The aptamer targets PDGF, which controls pericytes and regulates vascular maturation. 

Twenty-two patients were enrolled in the dose-escalating, uncontrolled, single- and multiple-dose, multicenter phase 1 study. The patients had predominantly or minimally classic subfoveal neovascular AMD 5 disc areas or less in total lesion size. Subjects received either one injection of 0.03 mg of the aptamer/eye and three monthly injections of ranibizumab 0.5 mg/eye (n = 3), or three monthly injections of one of four doses of the aptamer (0.03, 0.3, 1.5, or 3 mg/eye) and ranibizumab (0.5 mg/eye) (n = 3-8/doses). The end point was the presence of a dose-limiting response; the results were evaluated at 12 weeks, Dr. Boyer said. 

At week 12, 60% of patients had a three-line gain in visual acuity (VA) and decreased central foveal thickness. An early increase in VA at 4 weeks was maintained at 12 weeks as was the decrease in CNV. There was 86% regression of neovascularization, according to Dr. Boyer. 

The results indicated that the aptamer, combined with ranibizumab in patients with subfoveal neovascular AMD, was well tolerated. 

“This PDGF therapy inhibits pericyte recruitment, strips pericytes in mature new vessels, induces regression in models of anti-VEGF therapy, enhances inhibition of new vessels when used with anti-VEGF therapy, and showed potential bioactivity,” Dr. Boyer concluded. “Another confirmatory trial is warranted.” 

A phase I study of an intravitreal anti-platelet-derived growth factor (PDGF) aptamer (E10030, Ophthotech) that targets pericytes, evaluated in combination therapy with ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (AMD), indicated that the drug is safe and seems to have biologic activity against choroidal neovascularization (CNV), said David Boyer, MD, of Retina-Vitreous Associates, Beverly Hills.