NAV

Aflibercept

Identification

Summary

Afliberceptis 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是一种重组蛋白组成的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
蛋白质平均体重
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.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug events
Improve clinical decision support with information oncontraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
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
binder
 Humans
APlacenta growth factor
binder
 Humans
AVascular endothelial growth factor B
binder
 Humans
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
Improve decision support & research outcomes
With structured adverse effects data, including:blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
Toxicity

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
药物基因组学效应/ adrBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug InteractionsLearn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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.
Drug Interaction
Integrate drug-drug
interactions in your software
Alendronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Aflibercept is combined with Alendronic acid.
Clodronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Aflibercept is combined with Clodronic acid.
Etidronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Aflibercept is combined with Etidronic acid.
Ibandronate The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Aflibercept is combined with Ibandronate.
Pamidronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Aflibercept is combined with Pamidronic acid.
Risedronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Aflibercept is combined with Risedronic acid.
Tiludronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Aflibercept is combined with Tiludronic acid.
Zoledronic acid The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Aflibercept is combined with Zoledronic acid.
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
No interactions found.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image
Eylea Injection, solution 40 mg/ml Intravitreal 拜耳公司 2016-09-08 Not applicable EU flag
Eylea Solution 2 mg / 0.05 mL Intravitreal Bayer 2020-11-17 Not applicable Canada flag
Eylea Solution 2 mg / 0.05 mL Intravitreal Bayer 2013-12-23 Not applicable Canada flag
Eylea Injection, solution 40 mg/1mL Intravitreal Regeneron Pharmaceuticals, Inc. 2011-11-21 Not applicable US flag
Eylea Injection, solution 40 mg/ml Intravitreal 拜耳公司 2016-09-08 Not applicable EU flag
Zaltrap Solution, concentrate 100 mg/4mL Intravenous sanofi-aventis U.S. LLC 2012-08-03 Not applicable US flag
Zaltrap Injection, solution, concentrate 25 mg/ml Intravenous SANOFI WINTHROP INDUSTRIE 2016-09-08 Not applicable EU flag
Zaltrap Solution 200 mg / 8 mL Intravenous Sanofi Aventis 2014-05-08 2020-07-13 Canada flag
Zaltrap Solution, concentrate 200 mg/8mL Intravenous sanofi-aventis U.S. LLC 2012-08-03 Not applicable US flag
Zaltrap Injection, solution, concentrate 25 mg/ml Intravenous SANOFI WINTHROP INDUSTRIE 2016-09-08 Not applicable EU flag

Categories

ATC Codes
S01LA05 — Aflibercept L01XX44 — Aflibercept
Drug Categories
Chemical TaxonomyProvided byClassyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
有机酸
Class
碳水化合物食品xylic 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

通用再保险公司ferences
  1. 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]
  2. 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]
KEGG Drug
D09574
PubChem Substance
347910379
RxNav
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 TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
4 Active Not Recruiting Treatment Diabetic Macular Edema (DME) 1
4 Completed Other Wet Macular Degeneration 1
4 Completed Prevention Diabetic Macular Edema (DME) 1
4 Completed Treatment Age - Related Macular Degeneration (AMD) 5
4 Completed Treatment Age - Related Macular Degeneration (AMD)/Polypoidal Choroidal Vasculopathy (PCV) 1
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
4 Completed Treatment Branch Retinal Vein Occlusion/Central Retinal Vein Occlusion (CRVO)/Diabetic Macular Edema (DME)/Retinal Vein Occlusion 1
4 Completed Treatment Central Retinal Vein Occlusion (CRVO) 2
4 Completed Treatment Chorioretinal Vascular Disease 1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Form Route Strength
Injection Intravitreal
Injection, solution Intravitreal 40 mg/1mL
Solution Intravitreal 2 mg / 0.05 mL
Injection, solution Intravitreal 40 mg/ml
Injection, solution Intravitreal
Injection, solution Intravitreal 2.0 mg/50mcl
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 25 MG/ML
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 100 mg/4ml
Injection Parenteral
Injection, solution, concentrate Intravenous 200 mg/8ml
Injection, solution, concentrate Intravenous
Solution Intravenous 25.0 mg/ml
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 flag
US7531173 No 2009-05-12 2026-02-02 US flag
US7374758 No 2008-05-20 2020-05-23 US flag
US7608261 No 2009-10-27 2027-06-14 US flag
US7070959 No 2006-07-04 2020-05-23 US flag
US7374757 No 2008-05-20 2020-05-23 US flag

Properties

State
Liquid
Experimental Properties
Property Value Source
water solubility >100 mg/mL MSDS

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets tounlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details 1.Vascular endothelial growth factor A
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
粘结剂
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
分子量
27042.205 Da
References
  1. 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]
Details 2.Placenta growth factor
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
粘结剂
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
分子量
24788.45 Da
References
  1. 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]
Details 3.Vascular endothelial growth factor B
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
粘结剂
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
分子量
21601.56 Da
References
  1. 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 at May 24, 2013 21:16 / Updated at January 28, 2023 12:29