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In a phase I study, E10030 (Ophthotech) combined with ranibizumab (Lucentis, Genentech) in patients with subfoveal neovascular age-related macular degeneration was well tolerated and seemed to have biologic activity against choroidal neovascularization, according to one ophthalmologist.
Fort Lauderdale, FL-A phase I study of E10030 (Ophthotech), an intravitreal anti-platelet-derived growth factor (PDGF) aptamer that targets pericytes, was evaluated in combination therapy with ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (AMD). The results indicated that the drug is well tolerated and seems to have biologic activity against choroidal neovascularization (CNV), according to David S. Boyer, MD, who reported the findings for the Ophthotech Study Group at the annual meeting of the Association for Research in Vision and Ophthalmology.
He then cited examples of patients who were treated four times with ranibizumab and experienced increased visual acuity with marked reductions in the volume of subretinal fluid and drying of the CNV but no reduction in the size of the neovascular tissue.
E10030 targets PDGF, which controls pericytes and regulates vascular maturation. In a corneal neovascularization model, when PDGF and VEGF were both blocked, the result is massive inhibition regression. Patients pretreated with a combination of anti-PDGF and anti-VEGF had dramatic inhibition of growth of neovascularization compared with monotherapy treatment with either agent. In patients with established blood vessels, again the combination therapy was more successful in controlling growth, he said.
"E10030 seems to target pericytes covering only neovascular tissue," he said and showed that in a treated group, the normal pericytes were unaffected by treatment.
In preclinical models, E10030, a pegylated aptamer, strips pericytes. It inhibits PDGF with picomolar affinity; it is very sensitive. The half life in treated animals translates to about 1 month in humans, he added.