Elapegademase

Identification

Name
Elapegademase
Accession Number
DB14712
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Recombinant Enzymes
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.[4] Elapegademase is generated in E. coli, developed by Leadiant Biosciences and FDA approved on October 5, 2018.[1, 5]

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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RevcoviInjection1.6 mg/1mLIntramuscularLeadiant Biosciences, Inc.2006-07-24Not applicableUs
Categories
UNII
9R3D3Y0UHS
CAS number
1709806-75-6

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 pegamedase bovine 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 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]

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.[6]

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 used previously.[1]

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.

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
DrugInteraction
Abicipar PegolThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Abicipar Pegol.
Antihemophilic Factor (Recombinant), PEGylatedThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Antihemophilic Factor (Recombinant), PEGylated.
Cepeginterferon alfa-2BThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Cepeginterferon alfa-2B.
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.
Egaptivon pegolThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Egaptivon pegol.
Eptacog alfa pegol (activated)The therapeutic efficacy of Elapegademase can be decreased when used in combination with Eptacog alfa pegol (activated).
GlycoPEG-GCSFThe therapeutic efficacy of Elapegademase can be decreased when used in combination with GlycoPEG-GCSF.
Heptaethylene Glycol, Peg330The therapeutic efficacy of Elapegademase can be decreased when used in combination with Heptaethylene Glycol, Peg330.
Insulin peglisproThe therapeutic efficacy of Elapegademase can be decreased when used in combination with Insulin peglispro.
Food Interactions
Not Available

References

General References
  1. Rare DR [Link]
  2. Globe News Wire [Link]
  3. NIH [Link]
  4. NIHS reports [File]
  5. WHO Drug Information 2017 [File]
  6. Revcovi information [File]
External Links
Not Available
FDA label
Download (145 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentADA-SCID / Adenosine 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

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

Drug created on October 09, 2018 09:55 / Updated on November 02, 2018 07:56