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| Primary information |
|---|
| ID | 10765 |
| Therapeutic ID | Th1177 |
| Protein Name | Elosulfase alfa |
| Sequence | >Th1177_Elosulfase_alfa
APQPPNILLLLMDDMGWGDLGVYGEPSRETPLCSPSRAALLTGRLPIRNGFYTTNAHARNLLKKAGYVSKIVGKWHLGHRPQFHPLKHGFNIPVYRDWEMVGRYYEEFPINLKTGEANLTFLYWAVDATHAPVYASKPFLGTSQRGRYGDVADNTFVFFTSDNGAALISAPEQGGSNGPFPGHVTAGQVSHQLGSIMDLFTTSLALAGLTLMDRPIFYYRGDTLMAATLGQHKAHFWTWTVTTHNLEDHTKLPLIFHLGRDPGERFPLSFEALVPAQPQLNVCNWAVMNWAPPGCEKLGKPNLDRMAAEGLLFPNFYSANAYTPQEIVGGIPDSEQLLPEDEWFGSPNCHFGPYDNKARPQIYLQEALDFIKRQARHHPFAVREIDDSIGKILELLQDLHLCGKQTTFEGGMREPALAWWPPSDRAIDGLNLLPTLLQGRNSWENFRQGIDFCPGQNVSGASAEYQEALSRITSVVQQHQCLTPPESIPKKCLWSH
|
| Molecular Weight | 110800 |
| Chemical Formula | C5020H7588N1364O1418S35 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | week 0: 7.52 min week 22: 35.9 min |
| Description | Elosulfase alfa is a synthetic version of the enzyme N-acetylgalactosamine-6-sulfatase. It was approved by the FDA in 2014 for the treatment of Morquio syndrome. Elosulfase alfa was developed by BioMarin Pharmaceutical Inc. and is marketed under the brand Vimizimâ„¢. The recommended dose is 2 mg per kg given intravenously over a minimum range of 3.5 to 4.5 hours, based on infusion volume, once every week. |
| Indication/Disease | Vimizim is a hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme indicated for patients with Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome). |
| Pharmacodynamics | AUC: 238 min x μg/mL, standard deviation 100. |
| Mechanism of Action | Mucopolysaccharidoses comprise a group of lysosomal storage disorders caused by the deficiency of specific lysosomal enzymes required for the catabolism of glycosaminoglycans (GAG). Mucopolysaccharidosis IVA (MPS IVA, Morquio A Syndrome) is characterized by the absence or marked reduction in N-acetylgalactosamine-6-sulfatase activity. The sulfatase activity deficiency results in the accumulation of the GAG substrates, KS and C6S, in the lysosomal compartment of cells throughout the body. The accumulation leads to widespread cellular, tissue, and organ dysfunction. Vimizim is intended to provide the exogenous enzyme N-acetylgalactosamine-6-sulfatase that will be taken up into the lysosomes and increase the catabolism of the GAGs KS and C6S. Elosulfase alfa uptake by cells into lysosomes is mediated by the binding of mannose-6-phosphate-terminated oligosaccharide chains of elosulfase alfa to mannose-6-phosphate receptors. In the absence of an animal disease model that recapitulates the human disease phenotype, elosulfase alfa pharmacological activity was evaluated using human primary chondrocytes from two MPS IVA patients. Treatment of MPS IVA chondrocytes with elosulfase alfa induced clearance of KS lysosomal storage from the chondrocytes. |
| Toxicity | NA |
| Metabolism | NA |
| Absorption | Cmax: 1.49 µg/mL, standard deviation 0.534. |
| 396 mL/kg, standard deviation 316. |
| Clearance | 10.0 mL/min/kg. (standard deviation: 3.73). |
| Categories | Enzymes; Alimentary Tract and Metabolism |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | N-acetylgalactosamine-6-sulfatase |
| Brand Name | Vimizim |
| Company | Bio Marin Pharmaceutical Inc. |
| Brand Description | Bio Marin Pharmaceutical Inc. |
| Prescribed For | Vimizim (elosulfase alfa) is indicated for patients with Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome). |
| Chemical Name | NA |
| Formulation | 5 mg/5mL |
| Physical Appearance | Injection, solution |
| Route of Administration | IV |
| Recommended Dosage | The recommended dose is 2 mg per kg given intravenously over a minimum range of 3.5 to 4.5 hours, based on infusion volume, once every week. Pre-treatment with antihistamines with or without antipyretics is recommended 30 to 60 minutes prior to the start of the infusion |
| Contraindication | NA |
| Side Effects | Anaphylaxis and hypersensitivity reactions. |
| Useful Link 1 | NA |
| Useful Link 2 | NA |
| Remarks | NA |