About

Substantial peer-reviewed research has found high concentrations of Vascular Endothelial Growth Factor ("VEGF") in the eyes of patients affected with AMD and diabetic retinopathy. VEGF is one of the major factors causing abnormal blood vessel growth in the eye; this blood vessel growth is known as "angiogenesis". These blood vessels leak fluid and blood into the eye, causing vision loss. In addition to its anti-angiogenic properties, Eyetech's anti-VEGF aptamer has anti-permeability properties that prevent blood vessels from leaking. Thus, the aptamer may have a strong effect in preventing and/or stopping leakage into the retina (including the central portion of the retina, known as the macula). This leakage is the cause of DME. By preventing leakage from blood vessels and stopping the growth of new blood vessels, Macugen™ (pegaptanib sodium) offers a potential two-pronged approach to the treatment of AMD and DME.

Since 1948, clinical and experimental evidence has led investigators to hypothesize that low oxygen levels (hypoxia) in the retina triggers the production and release of an angiogenic factor that induces neovascularization of the retina and iris.The putative angiogenic factor was termed Factor X and VEGF fulfills the criteria established for its identification. VEGF is made in the retina and its levels increase when the retina is hypoxic. The production of VEGF in the retina correlates with neovascularization of the retina, choroid and iris and the inhibition of VEGF with antibodies or soluble receptors prevent neovascularization of the retina, choroid and iris.

Data showing the inhibition of neovascularization and permeability by VEGF blockers support the clinical trials to investigate the inhibition of blood vessel growth and leakage in humans with macular degeneration and diabetic retinopathy.

Studies published in The New England Journal of Medicine and The American Journal of Ophthalmology have shown that vitreous levels of VEGF are very high in patients undergoing invasive vitreous surgery for proliferative neovascular diseases such as diabetic retinopathy, but are negligible for patients undergoing the same type of surgery for other non-proliferative, non-neovascularized diseases.

Injections of VEGF in the laboratory can reproduce much of the pathology of background diabetic retinopathy, including diabetic macular edema. Moreover, retinal VEGF are increased in human eyes with background retinopathy and high VEGF levels are co-localized to the areas of active vessel leakage. These data provide strong indirect support that VEGF is casual for diabetic macular edema. Diabetic macular edema is a disease of abnormal vessel permeability.

Key Points - There is pre-clinical evidence that VEGF may play an important role in ocular neovascularization and that inhibitors of VEGF, such as an anti-VEGF aptamer, could prevent or retard the disease process.

• Evidence suggests that VEGF could be the causative factor in retinal and choroidal neovascularization.

• VEGF is present at the site of macular degeneration and diabetic retinopathy in humans.

• High levels of VEGF are only present in the vitreous of humans in neovascular diseases, and not in diseases that are not caused by abnormal blood vessel growth.

• VEGF can cause abnormal blood vessel growth in the eye as the injection of this chemical causes ocular neovascularization.

• The inhibition of neovascularization in pre-clinical studies by VEGF blockers suggests that we may be able to inhibit blood vessel growth in humans with macular degeneration and diabetic retinopathy.

• Eyetech's anti-VEGF aptamer greatly inhibits retinal neovascularization by approximately 80% in the well-known ROP animal model.

• Diabetic macular edema is a disease of vascular permeability.

• Macugen™ (pegaptanib sodium) also has potent anti-permeability properties in the laboratory, which may be effective in treating diabetic macular edema.