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| Primary information |
|---|
| ID | 10644 |
| Therapeutic ID | Th1133 |
| Protein Name | Aflibercept |
| Sequence | >Th1133_Aflibercept
SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQTNTIIDVVLSPSHGIELSVGEKLVLNCTARTELNVGIDFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKFLSTLTIDGVTRSDQGLYTCAASSGLMTKKNSTFVRVHEKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG
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| Molecular Weight | 115000 |
| Chemical Formula | C4318H6788N1164O1304S32 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Intravitreal half life - 7.13 days |
| Description | Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor. It is a recombinant dimeric fusion glycoprotein that comprises (VEGF) binding portions from the extracellular domains of human VEGF receptors 1 and 2, this is fused to the Fc portion of human IgG1. It contains approximately 15% glycosylation to give a total molecular weight of 115 kDa (protein part = 96.9 kDa). It has 5 putative N-glycosylation sites on each polypeptide chain and the attached carbohydrates exhibit some degree of chain heterogeneity, including heterogeneity in terminal sialic acid residues, except at the site associated with the Fc domain, which is unsialylated |
| Indication/Disease | 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| After intravenous injection of aflibercept, the volume of distribution is 6 L. |
| 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. |
| Categories | Antineoplastic Agents and Ophthalmics |
| Patents Number | US7531173 |
| Date of Issue | 5-Dec-2009 |
| Date of Expiry | 2-Feb-2026 |
| Drug Interaction | NA |
| Target | Vascular endothelial growth factor A,Placenta growth factor,Vascular endothelial growth factor B |
| Brand Name | Zaltrap |
| Company | Sanofi and Regeneron Pharmaceuticals, Inc. |
| Brand Description | Sanofi and Regeneron Pharmaceuticals, Inc. |
| Prescribed For | metastatic colorectal cancer (mCRC) that is resistant to or has progressed following an oxaliplatin-containing regimen |
| Chemical Name | NA |
| Formulation | ZALTRAP is supplied in single-use vials of 100 mg per 4 ml and 200 mg per 8 ml formulated as 25 mg/mL ziv-aflibercept in polysorbate 20 (0.1%), sodium chloride (100 mM), sodium citrate (5 mM), sodium phosphate (5 mM), and sucrose (20%), in Water for Injection USP, at a pH of 6.2. |
| Physical Appearance | ZALTRAP is a sterile, clear, colorless to pale yellow, non-pyrogenic, preservative-free, solution for administration by Intravenous infusion. |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | 4 mg per kg as an intravenous (IV) infusion over 1 hour every two weeks. |
| Contraindication | NA |
| Side Effects | Hemorrhage, Gastrointestinal, Compromised Wound Healing, Fistula Formation, Hypertension, Arterial Thromboembolic Events, Proteinuria, Neutropenia and Neutropenic Complications, Diarrhea and Dehydration, Reversible Posterior Leukoencephalopathy Syndrome |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |