aflibercept

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Ligands
aflibercept

GtoPdb Ligand ID: 6786

Synonyms: AVE0005 | Eylea® | VEGF Trap | Zaltrap® | ziv-aflibercept

aflibercept is an approved drug (FDA (2011), EMA (2012))

Comment: Alfibercept is a fusion protein combining the Fc portion of human IgG with the ligand binding domains of the VEGRF1 and VEGRF2 receptors.

Biosimilars:
Patent protection for originator alfibercept was expected to expire earliest in Japan and China (2022), then in US (2023, if Regeneron's extended patent claims were accepted) and the EU (2025), and biosimilar development proceeded during the run-up to patent expiry [4]. Early examples included Momenta Pharmaceuticals/Mylan's M710MYL-1701P, Alteogen's ALT-L9 (a heat stabilised formulation with a predicted longer shelf-life than Eylea; NCT04058535), and Formycon/Santo Holdings' FYB203.

The table below lists Eylea biosimilars with regulatory approval.

Name	Trade name	Company	Clinical Phase	Indications
aflibercept-jbvf	Yesafili®	Biocon Biologics	UK MHRA & EMA (2023), FDA (2024)	As per originator reference product; interchangeable
aflibercept-yszy (SB15)	Opuviz®	Biogen	FDA (2024)	As per originator reference product; interchangeable
aflibercept-mrbb (FYB203)	Ahzantive®	Formycon/Klinge Biopharma	FDA (2024), EMA (2025)	As per originator reference product
aflibercept-abzv (SOK583A1)	Enzeevu®	Sandoz	FDA (2024)	As per originator reference product
aflibercept-ayyh (ABP 938) [3]	Pavblu ®	Amgen	FDA (2024)	As per originator reference product

Peptide Sequence
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCE ATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSG SEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT ISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

Peptide Sequence

SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCE
ATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSG
SEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR
TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKT
ISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS
RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

Post-translational Modification
This is a recombinant fusion protein comprising vascular endothelial growth factor (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2 fused to the Fc portion of human IgG1. It exists as a dimer, covalently linked by disulphide bridges.

Chemical Modification
Covalent disulphide bonds form between amino acids as follows: Intra peptide disulphide bonds (30-79, 124-185, 246-306, 352-410) Inter peptide disulphide bonds (214-214, 211-211)