Identification

Name
Agalsidase beta
Accession Number
DB00103  (BTD00075, BIOD00075)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Recombinant Enzymes
Description

Recombinant human alpha-galactosidase A. The mature protein is composed of 2 subunits of 398 residues. Protein is glycosylated and produced by CHO cells

Protein structure
Db00103
Protein chemical formula
C2029H3080N544O587S27
Protein average weight
45351.6 Da
Sequences
>DB00103 sequence
LDNGLARTPTMGWLHWERFMCNLDCQEEPDSCISEKLFMEMAELMVSEGWKDAGYEYLCI
DDCWMAPQRDSEGRLQADPQRFPHGIRQLANYVHSKGLKLGIYADVGNKTCAGFPGSFGY
YDIDAQTFADWGVDLLKFDGCYCDSLENLADGYKHMSLALNRTGRSIVYSCEWPLYMWPF
QKPNYTEIRQYCNHWRNFADIDDSWKSIKSILDWTSFNQERIVDVAGPGGWNDPDMLVIG
NFGLSWNQQVTQMALWAIMAAPLFMSNDLRHISPQAKALLQDKDVIAINQDPLGKQGYQL
RQGDNFEVWERPLSGLAWAVAMINRQEIGGPRSYTIAVASLGKGVACNPACFITQLLPVK
RKLGFYEWTSRLRSHINPTGTVLLQLENTMQMSLKDLL
Download FASTA Format
Synonyms
  • Agalsidase alfa
  • Alpha-D- galactoside galactohydrolase
  • Alpha-D-galactosidase A
  • Alpha-galactosidase A precursor
  • Melibiase
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FabrazymeInjection, powder, lyophilized, for solution5 mg/mLIntravenousGenzyme Corporation2008-12-17Not applicableUs
FabrazymeInjection, powder, for solution5 mgIntravenousGenzyme Europe Bv2001-08-03Not applicableEu
FabrazymeInjection, powder, for solution35 mgIntravenousGenzyme Europe Bv2001-08-03Not applicableEu
FabrazymePowder, for solution5 mgIntravenousSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2004-09-17Not applicableCanada
FabrazymeInjection, powder, for solution5 mgIntravenousGenzyme Europe Bv2001-08-03Not applicableEu
FabrazymeInjection, powder, for solution35 mgIntravenousGenzyme Europe Bv2001-08-03Not applicableEu
FabrazymeInjection, powder, lyophilized, for solution5 mg/mLIntravenousGenzyme Corporation2008-12-17Not applicableUs
FabrazymeInjection, powder, for solution5 mgIntravenousGenzyme Europe Bv2001-08-03Not applicableEu
FabrazymeInjection, powder, for solution35 mgIntravenousGenzyme Europe Bv2001-08-03Not applicableEu
FabrazymePowder, for solution35 mgIntravenousSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2004-04-08Not applicableCanada
Categories
UNII
RZD65TSM9U
CAS number
104138-64-9

Pharmacology

Indication

For treatment of Fabry's disease (alpha-galactosidase A deficiency)

Structured Indications
Pharmacodynamics

Used in the treatment of Fabry disease, an X-linked genetic disorder of glycosphingolipid metabolism. The disease is characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A, which leads to progressive accumulation of glycosphingolipids, predominantly GL-3, in many body tissues. Clinical manifestations of Fabry disease include renal failure, cardiomyopathy, and cerebrovascular accidents. Fabrazyme is intended to provide an exogenous source of alpha-galactosidase A and to limit the accumulation of these glycolipids in the tissues. Studies show unconclusive evidence for the clinical efficacy of either agalasidase alfa or agalasidase beta in preventing morbidity.

Mechanism of action

Alpha-galactosidase A catalyzes the hydrolysis of globotriaosylceramide (GL-3) and other a-galactyl-terminated neutral glycosphingolipids, such as galabiosylceramide and blood group B substances to ceramide dihexoside and galactose.

TargetActionsOrganism
AGlobotriaosylceramide
ligand
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

45-102 min

Clearance
  • 4.1 +/- 1.2 mL/min/kg [adult patients with Fabry disease,0.3 mg/kg, 1 infusion]
  • 4.6 +/- 2.2 mL/min/kg [adult patients with Fabry disease, 0.3 mg/kg, 5 infusions]
  • 2.1 +/- 0.7 mL/min/kg [adult patients with Fabry disease, 1 mg/kg, 1 infusion]
  • 3.2 +/- 2.6 mL/min/kg [adult patients with Fabry disease, 1 mg/kg, 5 infusions]
  • 0.8 +/- 0.3 mL/min/kg [adult patients with Fabry disease, 3 mg/kg, 1 infusion]
  • 0.8 +/- 0.4 mL/min/kg [adult patients with Fabry disease, 3 mg/kg, 5 infusions]
  • 1.8 +/- 0.8 mL/min/kg [Pediatric Patients with Fabry Disease, 1 mg/kg, 1-3 infusions]
  • 4.9 +/- 5.6 mL/min/kg [Pediatric Patients with Fabry Disease, 1 mg/kg, 7 infusions]
  • 2.3 +/- 2.2 mL/min/kg [Pediatric Patients with Fabry Disease, 1 mg/kg, 11 infusions]
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AmiodaroneThe therapeutic efficacy of Agalsidase beta can be decreased when used in combination with Amiodarone.Approved, Investigational
ChloroquineThe therapeutic efficacy of Agalsidase beta can be decreased when used in combination with Chloroquine.Approved, Investigational, Vet Approved
GentamicinThe therapeutic efficacy of Agalsidase beta can be decreased when used in combination with Gentamicin.Approved, Vet Approved
Food Interactions
Not Available

References

General References
  1. Schaefer RM, Tylki-Szymanska A, Hilz MJ: Enzyme replacement therapy for Fabry disease: a systematic review of available evidence. Drugs. 2009 Nov 12;69(16):2179-205. doi: 10.2165/11318300-000000000-00000. [PubMed:19852524]
  2. El Dib RP, Pastores GM: Enzyme replacement therapy for Anderson-Fabry disease. Cochrane Database Syst Rev. 2010 May 12;(5):CD006663. doi: 10.1002/14651858.CD006663.pub2. [PubMed:20464743]
  3. Lim-Melia ER, Kronn DF: Current enzyme replacement therapy for the treatment of lysosomal storage diseases. Pediatr Ann. 2009 Aug;38(8):448-55. [PubMed:19725195]
External Links
UniProt
P06280
Genbank
X14448
PubChem Substance
46508538
ChEMBL
CHEMBL2108888
PharmGKB
PA164746527
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Agalsidase_beta
ATC Codes
A16AB04 — Agalsidase betaA16AB03 — Agalsidase alfa
AHFS Codes
  • 44:00.00 — Enzymes
FDA label
Download (38.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentFabry's Disease2
2CompletedNot AvailableFabry's Disease1
2CompletedTreatmentFabry's Disease7
2TerminatedTreatmentChronic Kidney Disease, Stage IV (Severe) / Fabry's Disease1
3CompletedTreatmentFabry's Disease4
3RecruitingTreatmentFabry's Disease2
4CompletedNot AvailableFabry's Disease1
4CompletedTreatmentFabry's Disease6
4RecruitingTreatmentFabry's Disease1
4WithdrawnTreatmentFabry's Disease1
Not AvailableCompletedNot AvailableFabry's Disease / Proteinuria1
Not AvailableEnrolling by InvitationNot AvailableFabry's Disease1
Not AvailableNo Longer AvailableNot AvailableFabry's Disease1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Genzyme Inc.
  • Shire Inc.
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous35 mg
Injection, powder, for solutionIntravenous5 mg
Injection, powder, lyophilized, for solutionIntravenous5 mg/mL
Powder, for solutionIntravenous35 mg
Powder, for solutionIntravenous5 mg
Injection, solution, concentrateIntravenous1 mg/ml
SolutionIntravenous1 mg
Prices
Unit descriptionCostUnit
Fabrazyme 35 mg vial5403.6USD vial
Fabrazyme 5 mg vial771.6USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2265464No2007-06-262017-09-12Canada

Properties

State
Liquid
Experimental Properties
PropertyValueSource
hydrophobicity-0.307Not Available
isoelectric point5.17Not 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

Targets

1. Globotriaosylceramide
Kind
Group
Organism
Human
Pharmacological action
Yes
Actions
Ligand
References
  1. Schaefer RM, Tylki-Szymanska A, Hilz MJ: Enzyme replacement therapy for Fabry disease: a systematic review of available evidence. Drugs. 2009 Nov 12;69(16):2179-205. doi: 10.2165/11318300-000000000-00000. [PubMed:19852524]
  2. El Dib RP, Pastores GM: Enzyme replacement therapy for Anderson-Fabry disease. Cochrane Database Syst Rev. 2010 May 12;(5):CD006663. doi: 10.1002/14651858.CD006663.pub2. [PubMed:20464743]
  3. Lim-Melia ER, Kronn DF: Current enzyme replacement therapy for the treatment of lysosomal storage diseases. Pediatr Ann. 2009 Aug;38(8):448-55. [PubMed:19725195]

Drug created on June 13, 2005 07:24 / Updated on April 23, 2018 22:56