Durham, NC-A novel vascular endothelial growth factor receptor 2 (VEGF-R2) topical eye drop may revolutionize the treatment of neovascular age-related macular degeneration (AMD) by making intravitreal injections a thing of the past for certain patients.
A major advantage for this topical therapy (PAN-90806, PanOptica Inc.) is that the risks associated with intravitreal anti-VEGF injections to treat AMD would be eliminated. The drug was found to be efficacious for patients with wet AMD who presented with milder lesions, characterized by thinner subfield thickness and small area.
This molecule, according to Scott Cousins, MD, is a selective inhibitor of VEGF-R2 (50% inhibitory concentration, 1.27 nm). Dr. Cousins is the Robert Machemer Professor of Ophthalmology and Immunology, vice chairman for research, and director of the Duke Center for Macular Diseases, Duke Eye Center, Durham, NC.
In a phase I/II dose-ranging trial for neovascular AMD, Dr. Cousins and colleagues sought to assess the safety and tolerability of the drug, establish a topical maximal tolerated dose, and look for signals of biologic activity.
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In the stage 1 monotherapy study phase, 40 patients were treated with 1 of 5 doses of PAN-90806, ranging from 1 to 4 mg/ml once to twice daily for 8 weeks. In the stage 2 maintenance study phase, in which 10 patients participated, 1 intravitreal injection of ranibizumab (Lucentis, Genentech Inc.) was administered, followed by 1 mg/mL of PAN-90806 once daily for 12 weeks.
The administration of rescue ranibizumab injections was based on worsening of the visual acuity by 10 letters and findings of increased thickening on optical coherence tomography (OCT), Dr. Cousins explained.
A responder to PAN-90806 was defined as a patient who:
• did not need rescue therapy with ranibizumab;
• was able to continue the topical therapy without signs of toxicity;
• showed evidence of a clinical response on imaging that was reviewed by retina specialists masked to the treatment doses and agreement of at least 2 experts that there was a qualitative, clinically relevant, response regarding intra- and subretinal fluid, blood, lesion, size, and fluorescein leakage, and evidence of a Wisconsin Reading Center quantified anatomic response on OCT and fluorescein angiography.