Elapegademase

Identification

Summary

Elapegademase is a recombinant adenosine deaminase used to treat adenosine deaminase severe combined immune deficiency.

Brand Names

Oncaspar

Generic Name

Elapegademase

DrugBank Accession Number

DB14712

Background

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

• (74-SERINE (C>S),245-THREONINE (A>T))BOS TAURUS ADENOSINE DEAMINASE (BOVINE ADENOSINE AMINOHYDROLASE, EC=3.5.4.4)-(1-356)-PEPTIDE PRODUCED IN ESCHERICHIA COLI, AN AVERAGE OF 13 RESIDUES ARE SUBSTITUTED ON N.ALPHA..1ALANINE AND N6 OF LYSINE RESIDUES WITH
• (CYS74>SER,ALA245>THR)ADENOSINE DEAMINASE (BOS TAURUS, BOVINE)-(1-356)-PEPTIDE, PRODUCED IN ESCHERICHIA COLI, SUBSTITUTED ON N2 OF THE N-TERMINAL ALANYL RESIDUE (A1) AND ON N6 OF LYSYL RESIDUES (K) WITH AN AVERAGE OFAPPROXIMATELY 13 .OMEGA.-METHOXYPOLY(O
• Elapegademase
• Elapegademase-lvlr
• monomethoxypolyethylene glycol recombinant adenosine deaminase
• POLY(OXY-1,2-ETHANEDIYL), .ALPHA.-CARBOXY-.OMEGA.-METHOXY-, AMIDE WITH ADENOSINE DEAMINASE (SYNTHETIC)

External IDs

• EZN 2279
• EZN-2279
• EZN2279

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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

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Severe combined immunodeficiency syndrome caused by adenosine deaminase deficiency		••••••••••••	•••••• •••••••••		•••••••••• ••••••••

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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

Target	Actions	Organism
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

Pathways

Not Available

Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">

Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
Integrate drug-drug interactions in your software
Antihemophilic factor (recombinant), PEGylated	The therapeutic efficacy of Elapegademase can be decreased when used in combination with Antihemophilic factor (recombinant), PEGylated.
Certolizumab pegol	The therapeutic efficacy of Elapegademase can be decreased when used in combination with Certolizumab pegol.
Damoctocog alfa pegol	The therapeutic efficacy of Elapegademase can be decreased when used in combination with Damoctocog alfa pegol.
Lipegfilgrastim	The therapeutic efficacy of Elapegademase can be decreased when used in combination with Lipegfilgrastim.
Methoxy polyethylene glycol-epoetin beta	The therapeutic efficacy of Elapegademase can be decreased when used in combination with Methoxy polyethylene glycol-epoetin beta.

Food Interactions

No interactions found.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Revcovi	Injection	1.6 mg/1mL	Intramuscular	Chiesi USA, Inc.	2018-10-05	Not applicable
Revcovi	Injection	1.6 mg/1mL	Intramuscular	Leadiant Biosciences, Inc.	2018-10-05	2022-08-31

Categories

ATC Codes

L03AX21 — Elapegademase

• L03AX — Other immunostimulants
• L03A — IMMUNOSTIMULANTS
• L03 — IMMUNOSTIMULANTS
• L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Categories

• Adenosine Deaminase Inhibitors
• Adjuvants, Immunologic
• Amino Acids, Peptides, and Proteins
• Aminohydrolases
• Antineoplastic and Immunomodulating Agents
• Enzyme Inhibitors
• Enzyme Replacement Therapy
• Enzymes
• Enzymes and Coenzymes
• Hydrolases
• Nucleoside Deaminases
• Pegylated agents
• Proteins
• Recombinant Adenosine Deaminases
• Recombinant Proteins

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

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]

External Links

RxNav

2059218

Wikipedia

Elapegademase

FDA label

Download (145 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
3	Completed	Treatment	ADA-SCID / Adenosine Deaminase Deficiency / Severe Combined Immunodeficiency Syndrome	1
Not Available	Completed	Not Available	Adenosine Deaminase Deficiency / Severe Combined Immunodeficiency Syndrome	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection	Intramuscular	1.6 mg/1mL

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Not Available

Targets

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Details1. Adenosine

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]

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Drug created at October 09, 2018 15:55 / Updated at September 30, 2023 19:52