Compound Name:Ziv-afliberceptMolecular Target:VEGF, PIGRMolecular Structure:Fusion protein: IgG Fc, and ligand binding domains of VEGFR-1 and VEGFR-2Licensed Indication:Metastatic colorectal cancerManufacturer and/or Distributor:Regeneron/ Sanofi-AventisInitial FDA Approval:2012Summary:Ziv-aflibercept is a fusion protein construct consisting of the Fc portion of human IgG linked to the ligand binding domains of the VEGRF-1 and VEGRF-2 receptors. It binds with high affinity to (vascular endothelial growth factor) VEGF-A, VEGF-B, (placental growth factor) PlGF-1 and PlGF-2, and inhibits neovascularization and vascular permeability. It thus exerts an anti-tumor effect. It is the same medicine as aflibercept (Eylea®), which is marketed for treatment of macular degeneration and macular edema following central retinal vein occlusion. Ziv-aflibercept was approved for the treatment of metastatic colorectal cancer that has failed treatment with an oxaliplatin-containing regimen. It is indicated for use in conjunction with 5-fluorouracil, leucovorin, and irinotecan (FOLFORI). In a single phase III trial comparing regimens of FOLFORI with ziv-aflibercept or with placebo, the ziv-aflibercept group showed improved median overal survival and median progression-free survival. The major safety concerns are gastrointestingal hemorrhage, fistula formation or perforation, hypertension, arterial thromboses, proteinuria, neutropenia, severe diarrhea, reversible posterior leukoencephalopathy, and impaired wound healing.References

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