Macular degeneration agents

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Information about Macular degeneration agents

Macular degeneration is an age-related disease of the retina marked by progressive loss of central visual acuity that is usually due to neovascularization in the subretinal space. The vascularization is dependent, at least in part, on action of vascular endothelial growth factor (VEGF). Recently, several agents that specifically target VEGF have been developed and shown to slow the progression of neovascular or "wet" macular degeneration when given as intravitreal injections.

List of Macular degeneration agents

These agents include monoclonal antibodies to VEGF (bevacizumab, ranibizumab), aptamers (small oligonucleotides that bind to VEGF: pegaptanib), and fusion VEGF receptor proteins that act as a decoy of the circulating growth factor (aflibercept). All four agents are given as intravitreal injections every 4 to 8 weeks. Most adverse events of these agents are ocular and relate to their local injection. Systemic exposure is limited and ex-ocular adverse events are rare. Some of the agents have been implicated in cardiovascular or cerebrovascular thromoembolic events but these are uncommon. None of the drugs for macular degeneration have been implicated in causing hepatotoxicity, either serum enzyme elevations during treatment or clinically apparent liver injury, at least when administered by intravitreal injection. The lack of hepatotoxicity is probably due largely to the lack of significant systemic absorption and exposure. When given intravenously as therapy of neoplastic conditions, several have been linked to instances of liver injury.

Bevacizumab

Bevacizumab is a humanized monoclonal antibody to VEGF that is approved for use intravenously for metastatic colon, renal cell and non-small cell lung cancer and for brain glioblastoma. Bevacizumab has been used off label to treat macular degeneration and, in controlled trials, was as effective as ranibizumab in improving or stabilizing vision in persons with age-related neovascular (wet) macular degeneration.

Bevacizumab is available in vials of 100 and 400 mg in a concentration of 25 mg/mL under the brand name Avastin. The dosage used off label for macular degeneration is 1.25 mg (0.05 mL) once monthly by intravitreal injection.


Ranibizumab

Ranibizumab is a recombinant humanized monoclonal antibody fragment (Fab) to VEGF (similar to bevacizumab). It was approved for use in neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion and diabetic macular edema in 2006. Ranibizumab is available in single use vials of 0.5 mg/0.05 mL under the brand name Lucentis. The recommended dose is 0.5 mg once monthly by intravitreal injection.


Pegaptanib

Pegaptanib is a pegylated aptamer, a modified oligonucleotide which binds with and inactivates extracellular VEGF. It was approved for use in neovascular (wet) age-related macular degeneration in 2004. Pegaptanib is available in single use glass syringe of 0.3 mg/90 μL under the brand name Macugen. The recommended dose is 0.3 mg by intravitreal injection once every six weeks.


Aflibercept

Aflibercept is a unique fusion protein consisting of VEGF receptors 1 and 2 fused to the Fc portion of IgG that acts as a decoy receptor competing for the binding of endogenous VEGF. It was approved for use in neovascular age related macular degeneration and for macular edema after central retinal vein occlusion in 2011. Indications have been broadened and aflibercept is also approved for use in diabeteic macular edema and retinopathy. Aflibercept is available in single use vials of 2 mg/0.05 mL under the brand name Eylea. The initial recommended dose is 2 mg once monthly by intravitreal injection.

Aflibercept is also available in a form for parenteral administration (ziv-aflibercept: Zaltrap) which is approved for use in combination with other antineoplastic agents (fluorouracil, leucovorin and irinotecan: FOLFIRI) for metastatic colon cancer. Administration of FOLFIRI is associated with fairly high rates of serum ALT and AST elevations and with occasional liver related serious adverse events. The addition of ziv-aflibercept to FOLFIRI has not been associated with higher rates of either serum enzyme elevations or clinically apparent liver injury, but experience with this combination has been limited.

Drug class for Macular degeneration agents

Macular Degeneration Agents, Monoclonal Antibodies Template:Macular degeneration agents

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