aflibercept

Aflibercept is a recombinant fusion protein that acts as a decoy receptor for vascular endothelial growth factor (VEGF). It binds VEGF-A, VEGF-B, and placental growth factor (PlGF-1/2) with high affinity, preventing VEGF from activating its receptors and thereby inhibiting abnormal angiogenesis and vascular leakage. It is produced by recombinant DNA technology in Chinese hamster ovary cells.

In ophthalmology, aflibercept is formulated for intravitreal injection to treat neovascular (wet) age-related macular degeneration, diabetic macular edema, and macular edema following retinal vein occlusion. In oncology, the fusion protein is marketed as Zaltrap for metastatic colorectal cancer in combination with FOLFIRI after progression on oxaliplatin-containing therapy.

Dosing and administration vary by indication. Ophthalmic use involves 2 mg intravitreal injections, typically following a loading schedule with monthly injections and then less frequent dosing (such as every eight weeks) depending on response. For cancer, aflibercept is given as an intravenous infusion according to cancer chemotherapy regimens. Pharmacokinetically, the drug achieves systemic exposure when given intravenously, while intravitreal administration leads to local exposure in the eye with a different clearance profile.

Adverse effects can include ocular events such as conjunctival hemorrhage, eye pain, floaters, and increased intraocular pressure; endophthalmitis is a rare but serious risk. Systemic events may include hypertension and thromboembolic processes. As with other anti-VEGF therapies, treatment decisions rely on balancing therapeutic benefits with potential risks.

Development and regulatory history: aflibercept was developed by Regeneron Pharmaceuticals and Sanofi. It was approved by the U.S. Food and Drug Administration for wet AMD in 2011 and for metastatic colorectal cancer (as Zaltrap) in 2012.