Agalsidase beta

Identification

Summary

Agalsidase beta is a recombinant human alpha-galactosidase indicated to treat Fabry disease, a genetic deficiency in the enzyme leading to buildup of globotriaosylceramide.

Brand Names
Fabrazyme
Generic Name
Agalsidase beta
DrugBank Accession Number
DB00103
Background

Agalsidase beta is a recombinant human α-galactosidase A similar to agalsidase alfa. While patients generally do not experience a clinically significant difference in outcomes between the two drugs, some patients may experience greater benefit with agalsidase beta.1,2 Use of agalsidase beta has decreased in Europe, in favor of agalsidase alfa, after a contamination event in 2009.5

Agalsidase beta was granted FDA approval on 24 April 2003.6

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Recombinant Enzymes
Protein Structure
Db00103
Protein Chemical Formula
C2029H3080N544O587S27
Protein Average Weight
45351.6 Da
Sequences
>DB00103 sequence
LDNGLARTPTMGWLHWERFMCNLDCQEEPDSCISEKLFMEMAELMVSEGWKDAGYEYLCI
DDCWMAPQRDSEGRLQADPQRFPHGIRQLANYVHSKGLKLGIYADVGNKTCAGFPGSFGY
YDIDAQTFADWGVDLLKFDGCYCDSLENLADGYKHMSLALNRTGRSIVYSCEWPLYMWPF
QKPNYTEIRQYCNHWRNFADIDDSWKSIKSILDWTSFNQERIVDVAGPGGWNDPDMLVIG
NFGLSWNQQVTQMALWAIMAAPLFMSNDLRHISPQAKALLQDKDVIAINQDPLGKQGYQL
RQGDNFEVWERPLSGLAWAVAMINRQEIGGPRSYTIAVASLGKGVACNPACFITQLLPVK
RKLGFYEWTSRLRSHINPTGTVLLQLENTMQMSLKDLL
References:
  1. NCBI: Galactosidase Alpha Gene [Link]
Download FASTA Format
Synonyms
  • Agalsidasa beta
  • Agalsidase beta
  • Agalsidase beta (genetical recombination)

Pharmacology

Indication

Agalsidase beta is indicated in the treatment of Fabry disease.6

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Agalsidase beta is a recombinant human α-galactosidase A used as enzyme replacement therapy in the treatment of Fabry disease.[L16398] It has a long duration of action and a wide therapeutic index.6 Patients should be counselled regarding the risk of infusion related reactions and hypersensitivity.6

Mechanism of action

α-galactosidase A is uptaken by cells via the mannose 6 phosphate receptor.3 Agalsidase beta hydrolyzes globotriaosylceramide and other glycosphingolipids that would normally be hydrolyzed by endogenous α-galactosidase A.6 Preventing the accumulation of glycosphingolipids prevents or reduces the severity of manifestations of Fabry disease such as renal failure, cardiomyopathy, or cerebrovascular events.6

TargetActionsOrganism
AGlobotriaosylceramide
metabolizer
ligand
Humans
Absorption

A 1 mg/kg dose of agalsidase beta with a mean infusion length of 115 minutes reaches a Cmax 5.0 ± 1.1 µg/mL with an AUC of 496 ± 137 µg*min/mL.6

Volume of distribution

A 1 mg/kg dose of agalsidase beta with a mean infusion length of 115 minutes has a VSS of 112 ± 13 mL/kg.6

Protein binding

Data regarding the protein binding of agalsidase beta is not readily available.6

Metabolism

Data regarding the metabolism of agalsidase beta is not readily available.6 However, protein drugs are expected to be degraded by proteases and other catalytic enzymes to smaller peptides and amino acids.4

Route of elimination

After nonspecific proteolysis, the amino acids from protein drugs are reused for protein synthesis or further broken down and eliminated by the kidneys.4

Half-life

agalsidase beta has a half like of 67 ± 12 min for a 1 mg/kg dose with a mean infusion length of 115 minutes.6

Clearance

A 1 mg/kg dose of agalsidase beta with a mean infusion length of 115 minutes has a clearance of 2.1 ± 0.7 mL/min/kg.6

Adverse Effects
Medicalerrors
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Toxicity

Data regarding overdoses of agalsidase beta are not readily available.6 Patients experiencing an overdose of agalsidase beta may experience an increased incidence and severity of adverse effects.6 Overdose can be managed through the use of symptomatic and supportive measures.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AmiodaroneThe therapeutic efficacy of Agalsidase beta can be decreased when used in combination with Amiodarone.
ChloroquineThe therapeutic efficacy of Agalsidase beta can be decreased when used in combination with Chloroquine.
GentamicinThe therapeutic efficacy of Agalsidase beta can be decreased when used in combination with Gentamicin.
Interactions
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Food Interactions
No interactions found.

Products

Products
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FabrazymePowder, for solution35 mg / vialIntravenousSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2004-04-08Not applicableCanada flag
FabrazymeInjection, powder, for solution5 mgIntravenousGenzyme Europe Bv2016-09-08Not applicableEU flag
FabrazymeInjection, powder, for solution35 mgIntravenousGenzyme Europe Bv2016-09-08Not applicableEU flag
FabrazymeInjection, powder, lyophilized, for solution5 mg/1mLIntravenousGenzyme Corporation2008-12-17Not applicableUS flag
FabrazymePowder, for solution5 mg / vialIntravenousSanofi Genzyme, a Division of Sanofi Aventis Canada Inc2004-09-17Not applicableCanada flag
FabrazymeInjection, powder, for solution5 mgIntravenousGenzyme Europe Bv2016-09-08Not applicableEU flag
FabrazymeInjection, powder, for solution35 mgIntravenousGenzyme Europe Bv2016-09-08Not applicableEU flag
FabrazymeInjection, powder, for solution5 mgIntravenousGenzyme Europe Bv2016-09-08Not applicableEU flag
FabrazymeInjection, powder, for solution35 mgIntravenousGenzyme Europe Bv2016-09-08Not applicableEU flag
FabrazymeInjection, powder, lyophilized, for solution5 mg/1mLIntravenousGenzyme Corporation2008-12-17Not applicableUS flag

Categories

ATC Codes
A16AB04 — Agalsidase beta
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
RZD65TSM9U
CAS number
Not Available

References

General References
  1. Germain DP, Elliott PM, Falissard B, Fomin VV, Hilz MJ, Jovanovic A, Kantola I, Linhart A, Mignani R, Namdar M, Nowak A, Oliveira JP, Pieroni M, Viana-Baptista M, Wanner C, Spada M: The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts. Mol Genet Metab Rep. 2019 Feb 6;19:100454. doi: 10.1016/j.ymgmr.2019.100454. eCollection 2019 Jun. [Article]
  2. Wilcox WR, Feldt-Rasmussen U, Martins AM, Ortiz A, Lemay RM, Jovanovic A, Germain DP, Varas C, Nicholls K, Weidemann F, Hopkin RJ: Improvement of Fabry Disease-Related Gastrointestinal Symptoms in a Significant Proportion of Female Patients Treated with Agalsidase Beta: Data from the Fabry Registry. JIMD Rep. 2018;38:45-51. doi: 10.1007/8904_2017_28. Epub 2017 May 17. [Article]
  3. Prabakaran T, Nielsen R, Satchell SC, Mathieson PW, Feldt-Rasmussen U, Sorensen SS, Christensen EI: Mannose 6-phosphate receptor and sortilin mediated endocytosis of alpha-galactosidase A in kidney endothelial cells. PLoS One. 2012;7(6):e39975. doi: 10.1371/journal.pone.0039975. Epub 2012 Jun 29. [Article]
  4. Katsila T, Siskos AP, Tamvakopoulos C: Peptide and protein drugs: the study of their metabolism and catabolism by mass spectrometry. Mass Spectrom Rev. 2012 Jan-Feb;31(1):110-33. doi: 10.1002/mas.20340. Epub 2011 Jun 22. [Article]
  5. Pisani A, Riccio E, Sabbatini M: Agalsidase alfa and agalsidase beta in the treatment of Fabry disease: does the dose really matter? Genet Med. 2015 Jan;17(1):21-3. doi: 10.1038/gim.2014.79. Epub 2014 Jul 10. [Article]
  6. FDA Approved Drug Products: Fabrazyme Agalsidase Beta Intravenous Injection [Link]
UniProt
P06280
Genbank
X14448
PubChem Substance
46508538
RxNav
338817
ChEMBL
CHEMBL2108888
PharmGKB
PA164746527
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Alpha-galactosidase
AHFS Codes
  • 44:00.00 — Enzymes
FDA label
Download (38.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentFabry's Disease5
4RecruitingTreatmentAlpha Galactosidase A Deficiency / Fabry's Disease1
4WithdrawnTreatmentFabry's Disease2
3Active Not RecruitingTreatmentFabry's Disease1
3CompletedTreatmentFabry's Disease3
2CompletedTreatmentFabry's Disease3
2TerminatedTreatmentChronic Kidney Disease, Stage IV (Severe) / Fabry's Disease1
1CompletedTreatmentFabry's Disease1
Not AvailableCompletedNot AvailableFabry's Disease2
Not AvailableCompletedNot AvailableFabry's Disease / Proteinuria1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Genzyme Inc.
  • Shire Inc.
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous
Injection, powder, for solutionIntravenous35 mg
Injection, powder, for solutionIntravenous5 mg
Injection, powder, for solutionIntravenous; Parenteral
Injection, powder, lyophilized, for solutionIntravenous5 mg/1mL
Powder, for solutionIntravenous35 mg / vial
Powder, for solutionIntravenous5 mg / vial
InjectionParenteral
Injection, powder, lyophilized, for solutionIntravenous
SolutionSubcutaneous
Powder35 mg/1vial
Powder5 mg/1vial
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)Region
CA2265464No2007-06-262017-09-12Canada flag

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Drugtargets
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1. Globotriaosylceramide
Kind
Group
Organism
Humans
Pharmacological action
Yes
Actions
Metabolizer
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. [Article]
  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. [Article]
  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. [Article]
  4. FDA Approved Drug Products: Fabrazyme Agalsidase Beta Intravenous Injection [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transmembrane signaling receptor activity
Specific Function
Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate r...
Gene Name
M6PR
Uniprot ID
P20645
Uniprot Name
Cation-dependent mannose-6-phosphate receptor
Molecular Weight
30993.06 Da
References
  1. Prabakaran T, Nielsen R, Satchell SC, Mathieson PW, Feldt-Rasmussen U, Sorensen SS, Christensen EI: Mannose 6-phosphate receptor and sortilin mediated endocytosis of alpha-galactosidase A in kidney endothelial cells. PLoS One. 2012;7(6):e39975. doi: 10.1371/journal.pone.0039975. Epub 2012 Jun 29. [Article]
  2. EMA Summary of Product Characteristics: Replagal Agalsidase Alfa Intravenous Injection [Link]
  3. FDA Approved Drug Products: Fabrazyme Agalsidase Beta Intravenous Injection [Link]

Drug created on June 13, 2005 13:24 / Updated on May 15, 2021 12:14