How do anti-VEGF Agents Work?

Vascular endothelial growth factor (VEGF) is a factor normally found in the eye that helps to promote new blood vessel growth. As discussed in Question 59, prior to birth VEGF is believed to play a critical role in the development of blood vessels in the eye, as well as other parts of the body. Once a person is born, the role of VEGF is less clear. While VEGF still plays a role in normal physiologic activities in the body, it is also known to play a critical role in the development of abnormal blood vessels in the body. This has been demonstrated in numerous clinical trials in which various inhibitors of VEGF have led to prevention of various disease characteristics or prevention of the disease altogether.

Anti-VEGF agents, such as Lucentis of Avastin, work by blocking VEGF. VEGF is required for the growth of the abnormal new blood vessels associated with wet macular degeneration. Anti-VEGF agents either bind to circulating VEGF, preventing it from binding to its receptor, or anti-VEGF agents may actually block the receptor, preventing circulating VEGF from attaching to the receptor. VEGF must bind with its receptor to initiate its actions, such as blood vessel growth or increased leaking. Other anti-VEGF therapies currently under investigation may try to inhibit the production of VEGF on a molecular level—that is, before it is even made. All anti-VEGF therapies share the common goal of pre-venting VEGF from carrying out its actions.