Elosulfase alfa

Identification

Name
Elosulfase alfa
Accession Number
DB09051
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Recombinant Enzymes
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 Vimizim™. 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.

Protein structure
Db09051
Protein chemical formula
C5020H7588N1364O1418S34
Protein average weight
110800.0 Da
Sequences
>Elosulfase-alfa
APQPPNILLLLMDDMGWGDLGVYGEPSRETPLCSPSRAALLTGRLPIRNGFYTTNAHARN
LLKKAGYVSKIVGKWHLGHRPQFHPLKHGFNIPVYRDWEMVGRYYEEFPINLKTGEANLT
FLYWAVDATHAPVYASKPFLGTSQRGRYGDVADNTFVFFTSDNGAALISAPEQGGSNGPF
PGHVTAGQVSHQLGSIMDLFTTSLALAGLTLMDRPIFYYRGDTLMAATLGQHKAHFWTWT
VTTHNLEDHTKLPLIFHLGRDPGERFPLSFEALVPAQPQLNVCNWAVMNWAPPGCEKLGK
PNLDRMAAEGLLFPNFYSANAYTPQEIVGGIPDSEQLLPEDEWFGSPNCHFGPYDNKARP
QIYLQEALDFIKRQARHHPFAVREIDDSIGKILELLQDLHLCGKQTTFEGGMREPALAWW
PPSDRAIDGLNLLPTLLQGRNSWENFRQGIDFCPGQNVSGASAEYQEALSRITSVVQQHQ
CLTPPESIPKKCLWSH
Download FASTA Format
Synonyms
  • N-acetylgalactosamine-6-sulfatase
External IDs
BMN 110 / J1322 / rhGALNS
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VimizimSolution1 mgIntravenousBiomarin International Limited2014-08-27Not applicableCanada
VimizimInjection, solution, concentrate5 mg/5mLIntravenousBiomarin International Limited2014-02-14Not applicableUs
Categories
UNII
ODJ69JZG85
CAS number
9025-60-9

Pharmacology

Indication

Vimizim is a hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme indicated for patients with Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome).

Structured Indications
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.

Absorption

Cmax: 1.49 μg/mL, standard deviation 0.534.

Volume of distribution

396 mL/kg, standard deviation 316.

Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

week 0: 7.52 min week 22: 35.9 min

Clearance

10.0 mL/min/kg. (standard deviation: 3.73).

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Sanford M, Lo JH: Elosulfase alfa: first global approval. Drugs. 2014 Apr;74(6):713-8. doi: 10.1007/s40265-014-0210-z. [PubMed:24700469]
External Links
UniProt
P34059
KEGG Drug
D10333
PubChem Substance
347910399
ChEMBL
CHEMBL2108676
Drugs.com
Drugs.com Drug Page
Wikipedia
Elosulfase_alfa
ATC Codes
A16AB12 — Elosulfase alfa
AHFS Codes
  • 44:00.00 — Enzymes
FDA label
Download (290 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentMPS IV A1
1, 2TerminatedTreatmentMorquio A Syndrome / MPS IV A / Mucopolysaccharidosis IVA1
2CompletedTreatmentMorquio A Syndrome / MPS IVA / Mucopolysaccharidosis IVA1
2TerminatedTreatmentMorquio A Syndrome / MPS IVA / Mucopolysaccharidosis IVA2
3CompletedTreatmentMPS IV A1
3CompletedTreatmentMorquio A Syndrome / MPS IVA / Mucopolysaccharidosis IV A1
3Unknown StatusTreatmentMucopolysaccharidosis IVA (Morquio A Syndrome)1
Not AvailableApproved for MarketingNot AvailableMorquio A Syndrome / MPS IVA / Mucopolysaccharidosis IVA1
Not AvailableNot Yet RecruitingNot AvailableMucopolysaccharidosis IV A1
Not AvailableRecruitingNot AvailableMorquio A Syndrome / MPS IVA / Mucopolysaccharidosis IV Type A1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solution, concentrateIntravenous5 mg/5mL
SolutionIntravenous1 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

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

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Other
General Function
Sulfuric ester hydrolase activity
Specific Function
Not Available
Gene Name
GALNS
Uniprot ID
P34059
Uniprot Name
N-acetylgalactosamine-6-sulfatase
Molecular Weight
58025.575 Da
References
  1. Sanford M, Lo JH: Elosulfase alfa: first global approval. Drugs. 2014 Apr;74(6):713-8. doi: 10.1007/s40265-014-0210-z. [PubMed:24700469]

Drug created on May 06, 2015 13:53 / Updated on January 14, 2018 10:04