Elapegademase

Identification

Name
Elapegademase
Accession Number
DB14712
Description

Elapegademase is a PEGylated recombinant adenosine deaminase. It can be defined molecularly as a genetically modified bovine adenosine deaminase with a modification in cysteine 74 for serine and with about 13 methoxy polyethylene glycol chains bound via carbonyl group in alanine and lysine residues.5 Elapegademase is generated in E. coli, developed by Leadiant Biosciences and FDA approved on October 5, 2018.1,6

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Recombinant Enzymes
Protein Chemical Formula
C1797H2795N477O544S12
Protein Average Weight
115000.0 Da
Sequences
>>Elapegademase<<<
AQTPAFNKPKVELHVHLDGAIKPETILYYGRKRGIALPADTPEELQNIIGMDKPLSLPEF
LAKFDYYMPAIAGSREAVKRIAYEFVEMKAKDGVVYVEVRYSPHLLANSKVEPIPWNQAE
GDLTPDEVVSLVNQGLQEGERDFGVKVRSILCCMRHQPSWSSEVVELCKKYREQTVVAID
LAGDETIEGSSLFPGHVKAYAEAVKSGVHRTVHAGEVGSANVVKEAVDTLKTERLGHGYH
TLEDTTLYNRLRQENMHFEVCPWSSYLTGAWKPDTEHPVVRFKNDQVNYSLNTDDPLIFK
STLDTDYQMTKNEMGFTEEEFKRLNINAAKSSFLPEDEKKELLDLLYKAYGMPSPA
References:
  1. NIHS reports [File]
Download FASTA Format
Synonyms
  • Elapegademase-lvlr
External IDs
  • EZN-2279

Pharmacology

Indication

Elapegademase is approved for the treatment of adenosine deaminase severe combined immune deficiency (ADA-SCID) in pediatric and adult patients.1 This condition was previously treated by the use of bovine pegamedase as part of an enzyme replacement therapy.2

ADA-SCID is a genetically inherited disorder that is very rare and characterized by a deficiency in the adenosine deaminase enzyme. The patients suffering from this disease often present with a compromised immune system. This condition is characterized by very low levels of white blood cells and immunoglobulin levels which results in severe and recurring infections.3

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

In clinical trials, elapegademase was shown to increase adenosine deaminase activity while reducing the concentrations of toxic metabolites which are the hallmark of ADA-SCID. As well, it was shown to improve the total lymphocyte count.7

Mechanism of action

The ADA-SCID is caused by the presence of mutations in the ADA gene which is responsible for the synthesis of adenosine deaminase. This enzyme is found throughout the body but it is mainly active in lymphocytes. The normal function of adenosine deaminase is to eliminate deoxyadenosine, created when DNA is degraded, by converting it into deoxyinosine. This degradation process is very important as deoxyadenosine is cytotoxic, especially for lymphocytes. Immature lymphocytes are particularly vulnerable as deoxyadenosine kills them before maturation making them unable to produce their immune function.3

Therefore, based on the causes of ADA-SCID, elapegademase works by supplementing the levels of adenosine deaminase. Being a recombinant and an E. coli-produced molecule, the use of this drug eliminates the need to source the enzyme from animals, as it was previously.1

TargetActionsOrganism
AAdenosine
metabolizer
Humans
Absorption

Elapegademase is administered intramuscularly and the reported Tmax, Cmax and AUC are approximately 60 hours, 240 mmol.h/L and 33000 hr.mmol/L as reported during a week.Label

Volume of distribution

This pharmacokinetic property has not been fully studied.

Protein binding

This pharmacokinetic property is not significant as the main effect is in the blood cells.

Metabolism

Metabolism studies have not been performed but it is thought to be degraded by proteases to small peptides and individual amino acids.

Route of elimination

This pharmacokinetic property has not been fully studied.

Half-life

This pharmacokinetic property has not been fully studied.

Clearance

This pharmacokinetic property has not been fully studied.

Adverse Effects
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Toxicity

As elapegademase is a therapeutic protein, there is a potential risk of immunogenicity.

There are no studies related to overdose but the highest weekly prescribed dose in clinical trials was 0.4 mg/kg. In nonclinical studies, a dosage of 1.8 fold of the clinical dose produced a slight increase in the activated partial thromboplastin time.Label

Affected organisms
  • Humans
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
Antihemophilic Factor (Recombinant), PEGylatedThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Antihemophilic Factor (Recombinant), PEGylated.
Certolizumab pegolThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Certolizumab pegol.
Damoctocog alfa pegolThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Damoctocog alfa pegol.
LipegfilgrastimThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Lipegfilgrastim.
Methoxy polyethylene glycol-epoetin betaThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Methoxy polyethylene glycol-epoetin beta.
Nonacog beta pegolThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Nonacog beta pegol.
PegademaseThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Pegademase.
PegaptanibThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Pegaptanib.
PegaspargaseThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Pegaspargase.
PegfilgrastimThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Pegfilgrastim.
Additional Data Available
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  • Severity
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  • Evidence Level
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  • Action
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Food Interactions
Not Available

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RevcoviInjection1.6 mg/1mLIntramuscularLeadiant Biosciences, Inc.2018-10-05Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number
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    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
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    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L03AX21 — Elapegademase
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

Chemical Identifiers

UNII
9R3D3Y0UHS
CAS number
1709806-75-6

References

General References
  1. Rare DR [Link]
  2. Globe News Wire [Link]
  3. NIH [Link]
  4. FDA Approved Drug Products: Revcovi (elapegademase-lvlr) for intramuscular injection [Link]
  5. NIHS reports [File]
  6. WHO Drug Information 2017 [File]
  7. Revcovi information [File]
RxNav
2059218
Wikipedia
Elapegademase
FDA label
Download (145 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentADA-SCID / Adenosine Deaminase Deficiency / Severe Combined Immunodeficiency1
Not AvailableRecruitingNot AvailableAdenosine Deaminase Deficiency / Severe Combined Immunodeficiency1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntramuscular1.6 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

Kind
Small molecule
Organism
Humans
Pharmacological action
Yes
Actions
Metabolizer
Curator comments
Note: Adenosine deaminase is involved in the metabolism of a number of purines, including adenosine. Adenosine was chosen as a representative molecule.
References
  1. FDA Approved Drug Products: Revcovi (elapegademase-lvlr) for intramuscular injection [Link]

Drug created on October 09, 2018 09:55 / Updated on August 01, 2020 06:25

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