| Primary information |
|---|
| ThPP ID | Th1133 |
| Therapeutic Peptide/Protein Name | Aflibercept |
| Sequence | SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDTLI view full sequnce in fasta |
| Functional Classification | Ib |
| Molecular Weight | 115000 |
| Chemical Formula | C4318H6788N1164O1304S32 |
| Isoelectric Point | N.A. |
| Hydrophobicity | N.A. |
| Melting Point (℃) | N.A. |
| 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. |
| Volume of Distribution | After Intravenous infusion 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 | US7306799 |
| Date of Issue | 26/03/09 |
| Date of Expiry | 24/05/24 |
| Drug Interaction | N.A. |
| Target | Vascular endothelial growth factor A,Placenta growth factor,Vascular endothelial growth factor B |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Eylea |
| Company | Regeneron Pharmaceuticals |
| Brand Discription | EYLEA (aflibercept) is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 formulated as an iso-osmotic solution for intravitreal administration. Aflibercept is a dimeric glycoprotein with a protein molecular weight of 97 kilodaltons (kDa) and contains glycosylation, constituting an additional 15% of the total molecular mass, resulting in a total molecular weight of 115 kDa. Aflibercept is produced in recombinant Chinese hamster ovary (CHO) cells. |
| Prescribed for | Neovascular (Wet) Age-Related Macular Degeneration (AMD), Macular Edema Following Central Retinal Vein Occlusion (CRVO) |
| Chemical Name | N.A. |
| Formulation | EYLEA is supplied as a preservative-free, sterile, aqueous solution in a single-use, glass vial designed to deliver 0.05 mL (50 microliters) of EYLEA (40 mg/mL in 10 mM sodium phosphate, 40 mM sodium chloride, 0.03% polysorbate 20, and 5% sucrose, pH 6.2). |
| Physcial Appearnce | EYLEA is a sterile, clear, and colorless to pale yellow solution. |
| Route of Administration | Intravitreal Injection |
| Recommended Dosage | The recommended dose for EYLEA is 2 mg (0.05 mL or 50 microliters) administered by intravitreal injection every 4 weeks (monthly) for the first 12 weeks (3 months), followed by 2 mg (0.05 mL) via intravitreal injection once every 8 weeks (2 months). |
| Contraindication | ocular or periocular infections, active intraocular inflammation, Hypersensitivity |
| Side Effects | Endophthalmitis and retinal detachments, Increased intraocular pressure, Thromboembolic events |
| Useful Link | http://www.rxlist.com/eylea-drug.htm http://www.eylea.com/international/?p=/eylea-home/index.php http://www.drugs.com/eylea.html |
| PubMed ID | 25646034, 25634529, 25632361, 25627086, 23673444, 23560774 |
| 3-D Structure | Th1133 (View) or (Download) |