|Pegaptanib is a pegylated anti-VEGF aptamer, a single strand of nucleic acid that binds with specificity to a particular target. Pegaptanib specifically binds to VEGF 165, a protein that plays a critical role in angiogenesis (the formation of new blood vessels) and increased permeability (leakage from blood vessels), two of the primary pathological processes responsible for the vision loss associated with neovascular AMD. [Wikipedia]
Gilead Sciences Inc.
For the treatment of neovascular (wet) age-related macular degeneration.
Pegaptanib is a selective vascular endothelial growth factor (VEGF) antagonist. VEGF is a secreted protein that selectively binds and activates its receptors located primarily on the surface of vascular endothelial cells. VEGF induces angiogenesis, and increases vascular permeability and inflammation, all of which are thought to contribute to the progression of the neovascular (wet) form of age-related macular degeneration (AMD), a leading cause of blindness. VEGF has been implicated in blood retinal barrier breakdown and pathological ocular neovascularization.
mechanism of action
Pegaptanib binds to the major pathological VEGF isoform, extracellular VEGF165, thereby inhibiting VEGF165 binding to its VEGF receptors. The inhibition of VEGF164, the rodent counterpart of human VEGF165, was effective at suppressing pathological neovascularization.
Based on preclinical data, pegaptanib is metabolized by endo- and exonucleases.
In animals, pegaptanib is slowly absorbed into the systemic circulation from the eye after intravitreous administration.
In humans, after a 3 mg monocular dose (10 times the recommended dose), the average (± standard deviation) apparent plasma half-life of pegaptanib is 10 (± 4) days.