Aflibercept
Identification
- Summary
Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor used to treat Neovascular (Wet) Age-Related Macular Degeneration (AMD), various types of macular edema and diabetic retinopathy.
- Brand Names
- Eylea, Zaltrap
- Generic Name
- Aflibercept
- DrugBank Accession Number
- DB08885
- Background
Aflibercept is a recombinant protein composed of the binding domains of two human vascular endothelial growth factor (VEGF) receptors fused with the Fc region of human immunoglobulin gamma 1 (IgG1). Structurally, Aflibercept is a dimeric glycoprotein with a protein molecular weight of 96.9 kilo Daltons (kDa). It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa. All five putative N-glycosylation sites on each polypeptide chain predicted by the primary sequence can be occupied with carbohydrate and exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the single unsialylated site associated with the Fc domain. Aflibercept, as an ophthalmic agent, is used in the treatment of macular edema following Central Retinal Vein Occlusion (CRVO) and neovascular Age-Related Macular Degeneration (AMD). Ziv-aflibercept, under the brand name Zaltrap, was developed as an injection for treatment of metastatic colorectal cancer. FDA approved in November 18, 2011 and EMA approved in November 2012.
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Fusion proteins - Protein Chemical Formula
- C4318H6788N1164O1304S32
- Protein Average Weight
- 115000.0 Da (with glycosylation)
- Sequences
> Protein sequence for aflibercept SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDS RKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKL VLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQ GLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPS DIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNH YTQKSLSLSPG
Download FASTA Format- Synonyms
- Aflibercept
- Aflibercept (genetical recombination)
- Ziv-aflibercept
- External IDs
- AVE 0005
- AVE 005
- AVE-0005
- AVE0005
- Bay 86-5321
- BAY-865321
- Bay86-5321
Pharmacology
- Indication
The opthalmic agent is used for the treatment of neovascular (wet) age-related mascular degeneration (AMD) and macular edema following central retinal vein occulsion (CRVO). The systemic injection, known as ziv-aflibercept, in combination with 5-fluorouracil, leucovorin, irinotecan-(FOLFIRI), is for the treatment of metastatic colorectal cancer that is resistant to or progressed following treatment with oxaliplatin.
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:Accelerate your drug discovery research with our fully connected ADMET dataset- Associated Conditions
- Branch Retinal Vein Occlusion With Macular Edema
- Central Retinal Vein Occlusion With Macular Edema
- Diabetic Macular Edema (DME)
- Diabetic Retinopathy (DR)
- Macular Edema
- Metastatic Colorectal Cancer (MCRC)
- Myopic Choroidal Neovascularization
- Neovascular Age Related Macular Degeneration
- Wet Age Related Macular Degeneration
- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- Pharmacodynamics
Compared to other anti-VEGF drugs like bevacizumab and ranibizumab, aflibercept has a higher binding affinity to VEGF-A (Kd = 0.5 pM).
- Mechanism of action
Ablibercept is a recombinant fusion protein that acts as a decoy receptor for the ligands, vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF). It prevents these ligands to binding to endothelial receptors, VEGFR-1 and VEGFR-2, to suppress neovascularization and decrease vascular permeability. This ultimately will slow vision loss or the progression of metastatic colorectal cancer.
Target Actions Organism AVascular endothelial growth factor A binderHumans APlacenta growth factor binderHumans AVascular endothelial growth factor B binderHumans - Absorption
In patients with wet AMD and CRVO, the mean peak plasma concentration (Cmax) was 0.02 mcg/mL and 0.05 mcg/mL respectively. These concentrations were reached in 1 to 3 days. Aflibercept did not accumulate when administered as repeated doses intravitreally every 4 weeks.
- Volume of distribution
After intravenous injection of aflibercept, the volume of distribution is 6 L.
- Protein binding
Not Available
- Metabolism
Because aflibercept is a protein, it is expected to be broken down via proteolysis into smaller peptides and amino acids. The cytochrome P450 enzyme system is not involved in the metabolism of aflibercept.
- Route of elimination
Via kidney and liver
- Half-life
Intravitreal half-life= 7.13 days in humans; Terminal elimination half-life of free aflibercept in plasma was 5 to 6 days after IV injection of 2 - 4 mg/kg dose.
- Clearance
When cancer patients were given 2-9 mg/kg every 2 or 3 week; 1 hour IV infusion of aflibercept the typical estimated clearances were as follows: CL of free aflibercept (CLf) = 0.88 L/day; CL of bound aflibercept (CLf) = 0.19 L/day; Patients clear free aflibercept faster if they had low albumin or high alkaline phosphatase levels.
- Adverse Effects
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For all intravitreal VEGF inhibitors, there is increased risk of stroke and myocardial infarction. An increase in intraocular pressure may also occur. When used intravenously, most common adverse reactions were leukopenia, diarrhea, neutropenia, proteinuria, AST increased, stomatitis, fatigue, thrombocytopenia, ALT increased, hypertension, weight decreased, decreased appetite, epistaxis, abdominal pain, dysphonia, serum creatinine increased, and headache.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Eylea Injection, solution 40 mg/ml Intravitreal Bayer Ag 2016-09-08 Not applicable EU 
Eylea Injection, solution 40 mg/ml Intravitreal Bayer Ag 2016-09-08 Not applicable EU Eylea Solution 40 mg / mL Intravitreal Bayer 2020-11-17 Not applicable Canada 
Eylea Injection, solution 40 mg/1mL Intravitreal Regeneron Pharmaceuticals, Inc. 2011-11-21 Not applicable US 
Eylea Solution 40 mg / mL Intravitreal Bayer 2013-12-23 Not applicable Canada Zaltrap Solution 200 mg / 8 mL Intravenous Sanofi Aventis 2014-05-08 2020-07-13 Canada Zaltrap Injection, solution, concentrate 25 mg/ml Intravenous Sanofi Aventis Groupe 2016-09-08 Not applicable EU Zaltrap Solution, concentrate 100 mg/4mL Intravenous sanofi-aventis U.S. LLC 2012-08-03 Not applicable US Zaltrap Solution 100 mg / 4 mL Intravenous Sanofi Aventis 2014-05-08 2020-07-13 Canada Zaltrap Injection, solution, concentrate 25 mg/ml Intravenous Sanofi Aventis Groupe 2016-09-08 Not applicable EU
Categories
- ATC Codes
- S01LA05 — Aflibercept
- S01LA — Antineovascularisation agents
- S01L — OCULAR VASCULAR DISORDER AGENTS
- S01 — OPHTHALMOLOGICALS
- S — SENSORY ORGANS
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antineoplastic and Immunomodulating Agents
- Antineovascularisation Agents
- EENT Drugs, Miscellaneous
- Enzymes
- Enzymes and Coenzymes
- Membrane Proteins
- Ocular Vascular Disorder Agents
- Ophthalmics
- Ophthalmologicals
- Phosphotransferases
- Phosphotransferases (Alcohol Group Acceptor)
- Protein Kinases
- Protein-Tyrosine Kinases
- Proteins
- Receptor Protein-Tyrosine Kinases
- Receptors, Growth Factor
- Receptors, Peptide
- Recombinant Proteins
- Sensory Organs
- Transferases
- Vascular Endothelial Growth Factor Inhibitor
- Vascular Endothelial Growth Factor Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 15C2VL427D
- CAS number
- 862111-32-8
References
- General References
- Freund KB, Mrejen S, Gallego-Pinazo R: An update on the pharmacotherapy of neovascular age-related macular degeneration. Expert Opin Pharmacother. 2013 Jun;14(8):1017-28. doi: 10.1517/14656566.2013.787410. Epub 2013 Apr 8. [Article]
- Thai HT, Veyrat-Follet C, Mentre F, Comets E: Population pharmacokinetic analysis of free and bound aflibercept in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 Jul;72(1):167-80. doi: 10.1007/s00280-013-2182-1. Epub 2013 May 15. [Article]
- External Links
- KEGG Drug
- D09574
- PubChem Substance
- 347910379
- 1232150
- ChEMBL
- CHEMBL1742982
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Aflibercept
- FDA label
- Download (325 KB)
- MSDS
- Download (91.1 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Age Related Macular Degeneration (ARMD) / Polypoidal Choroidal Vasculopathy (PCV) 1 4 Active Not Recruiting Treatment Diabetic Macular Edema (DME) 2 4 Active Not Recruiting Treatment Diabetic Retinopathy (DR) 1 4 Completed Basic Science Neovascular Age Related Macular Degeneration 1 4 Completed Other Wet Macular Degeneration 1 4 Completed Prevention Diabetic Macular Edema (DME) 1 4 Completed Treatment Age - Related Macular Degeneration (AMD) 1 4 Completed Treatment Age Related Macular Degeneration (ARMD) 4 4 Completed Treatment AMD (With Persistent or Recurrent Fluid Despite Monthly Intravitreal Anti-VEGF Therapy) 1 4 Completed Treatment Anti Vascular Endothelial Growth Factor / Macular Degeneration 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravitreal Injection, solution Intravitreal Injection, solution Intravitreal 40 mg/1mL Injection, solution Intravitreal 40 mg/ml Solution Intravitreal 40 mg / mL Solution Intraocular 2 mg Injection Intravenous Injection, solution, concentrate Intravenous 25 mg/ml Injection, solution, concentrate Intravenous 25 mg/1ml Injection, solution, concentrate Intravenous; Parenteral Solution Intravenous 100 mg / 4 mL Solution Intravenous 200 mg / 8 mL Solution, concentrate Intravenous 100 mg/4mL Solution, concentrate Intravenous 200 mg/8mL Injection Parenteral Injection, solution, concentrate Intravenous Solution Ophthalmic 40 mg/1ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7306799 No 2007-12-11 2020-05-23 US US7531173 No 2009-05-12 2026-02-02 US US7374758 No 2008-05-20 2020-05-23 US US7608261 No 2009-10-27 2027-06-14 US US7070959 No 2006-07-04 2020-05-23 US US7374757 No 2008-05-20 2020-05-23 US
Properties
- State
- Liquid
- Experimental Properties
Property Value Source water solubility >100 mg/mL MSDS
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Vascular endothelial growth factor receptor binding
- Specific Function
- Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of...
- Gene Name
- VEGFA
- Uniprot ID
- P15692
- Uniprot Name
- Vascular endothelial growth factor A
- Molecular Weight
- 27042.205 Da
References
- Browning DJ, Kaiser PK, Rosenfeld PJ, Stewart MW: Aflibercept for age-related macular degeneration: a game-changer or quiet addition? Am J Ophthalmol. 2012 Aug;154(2):222-6. doi: 10.1016/j.ajo.2012.04.020. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Heparin binding
- Specific Function
- Growth factor active in angiogenesis and endothelial cell growth, stimulating their proliferation and migration. It binds to the receptor FLT1/VEGFR-1. Isoform PlGF-2 binds NRP1/neuropilin-1 and NR...
- Gene Name
- PGF
- Uniprot ID
- P49763
- Uniprot Name
- Placenta growth factor
- Molecular Weight
- 24788.45 Da
References
- Browning DJ, Kaiser PK, Rosenfeld PJ, Stewart MW: Aflibercept for age-related macular degeneration: a game-changer or quiet addition? Am J Ophthalmol. 2012 Aug;154(2):222-6. doi: 10.1016/j.ajo.2012.04.020. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Vascular endothelial growth factor receptor 1 binding
- Specific Function
- Growth factor for endothelial cells. VEGF-B167 binds heparin and neuropilin-1 whereas the binding to neuropilin-1 of VEGF-B186 is regulated by proteolysis.
- Gene Name
- VEGFB
- Uniprot ID
- P49765
- Uniprot Name
- Vascular endothelial growth factor B
- Molecular Weight
- 21601.56 Da
References
- Browning DJ, Kaiser PK, Rosenfeld PJ, Stewart MW: Aflibercept for age-related macular degeneration: a game-changer or quiet addition? Am J Ophthalmol. 2012 Aug;154(2):222-6. doi: 10.1016/j.ajo.2012.04.020. [Article]
Drug created on May 24, 2013 21:16 / Updated on July 23, 2021 16:02