Eteplirsen

Identification

Summary

Eteplirsen is an antisense oligonucleotide used to treat Duchenne muscular dystrophy (DMD) only in patients who are confirmed to have a specific type of mutation.

Brand Names
Exondys
Generic Name
Eteplirsen
DrugBank Accession Number
DB06014
Background

Eteplirsen is a phosphoramidite morpholino sequence complementary to a portion of exon 51. 1 It exerts it's mechanism of action by forcing the exclusion of exon 51 from the mature DMD mRNA. 1

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Gene Therapies
Antisense oligonucleotides
Synonyms
  • (P-deoxy-P-(dimethylamino)](2',3'-dideoxy-2',3'-imino-2',3'-seco)(2'a→5')(C-m5U-C-C-A-A-C-A-m5U-C-A-A-G-G-A-A-G-A-m5U-G-G-C-A-m5U-m5U-m5U-C-m5U-A-G),5'-(P-(4-((2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)carbonyl)-1-piperazinyl)-N,N-dimethylphosphonamidate) RNA
  • Eteplirsen
External IDs
  • AVI-4658

Pharmacology

Indication

Eteplirsen is indicated for treatment of certain individuals with Duchenne muscular dystrophy (DMD). Its use is limited to those with a confirmed mutation of the DMD gene which would benefit from exon 51 skipping. Based on clinical studies showing increased dystrophin production in skeletal muscle in some patients given this drug, the above indication was approved under accelerated approval. Further confirmatory trials are required to demonstrate clinical benefit of eteplirsen.

Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:
Machine Learning
Data Science
Drug Discovery
Accelerate your drug discovery research with our fully connected ADMET dataset
Learn more
Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Contraindications & Blackbox Warnings
With our commercial data, access important information on dangerous risks, contraindications, and adverse effects.
Learn more
Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects
Learn more
Pharmacodynamics

The defining characteristic of DMD is lack of dystrophin, which is a protein that plays a vital role in maintaining muscle cell membrane integrity. (2) This is caused by a mutation in the DMD gene which leads to disruption of the translational reading frame, and ultimately in a non-functional protein. (2) Eteplirsen, is a targeted oligonucleotide that causes exon skipping of exon 51 and restores the translational reading frame. (2) The expected result is production of an internally deleted but functional dystrophin protein. (2)
Three clinical studies were done to evaluate eteplirsen. All patients in studies had a confirmed mutation of the DMD gene susceptible to exon 51 skipping. All patients treated with the drug produced messenger ribonucleic acid (mRNA) coding for an internally truncated dystrophin protein. In study 3, after 48 weeks of treatment with eteplirsen, the average dystrophin protein level was 0.44% of normal (what would be found in a healthy subject) compared to 0.16% of normal prior to treatment. There was a median increase of 0.1% in truncated dystrophin.

Mechanism of action

Eteplirsen, is a targeted oligonucleotide that causes exon skipping of exon 51 and restores the translational reading frame. (2) The expected result is production of an internally deleted but functional dystrophin protein. (2)

TargetActionsOrganism
ADMD-001 gene (exon 51 target site)
binding
Humans
Absorption

Not Available

Volume of distribution

Mean apparent volume of distribution = 600 mL/kg (value found following weekly intravenous infusion at a dose of 30mg/kg)

Protein binding

Studies suggest that plasma protein binding of eteplirsen is 6-17% in humans.

Metabolism

Metabolism of eteplirsen does not appear to occur in human hepatic microsomes.

Route of elimination

Two-thirds of eteplirsen is renally eliminated within 24 hours of intravenous administration.

Half-life

Mean half-life (dose of 30 mg/kg) = 3.3 hours, and mean half-life (dose of 50 mg/kg) = 3.2 hours (3)

Clearance

The kidneys are responsible for 65-70% of total eteplirsen clearance. (3) After 12 weeks of treatment at a dose of 30 mg/kg/week, total clearance was found to be 339 mL/hr/kg.

Adverse Effects
Medicalerrors
Reduce medical errors
and improve treatment outcomes with our comprehensive & structured data on drug adverse effects.
Learn more
Reduce medical errors & improve treatment outcomes with our adverse effects data
Learn more
Toxicity

Potential adverse effects of eteplirsen were determined in 2 studies: 1. A 24 week double-blind, placebo-controlled study, 2. An open label extension following the first study. In study 1, the following adverse effects occurred more frequently in 2 or more patients receiving eteplirsen compared to placebo: Balance disorder (38%), vomiting (38%), contact dermatitis (25%). These percentages represent crude frequencies due to the small sample of patients studied; therefore, they may not be representative of the general population. All patients in study 1 continued to participate in study 2. The following adverse effects occurred at a rate ≥10% among the 88 patients receiving ≥30 mg/kg/week of eteplirsen for up to 208 weeks in study 2: vomiting, contusion, excoriation, arthralgia, rash, pain at catheter site, and upper respiratory tract infections. These adverse events also occurred more frequently in patients in study 2 compared to patients in study 1 on the same dose of eteplirsen. Facial flushing, transient erythema, and elevated temperature have been reported to occur on the days of eteplirsen infusion.

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.
Not Available
Food Interactions
No interactions found.

Products

Products
Comprehensive & structured drug product info
From application numbers to product codes, connect different identifiers through our commercial datasets.
Learn more
Easily connect various identifiers back to our datasets
Learn more
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Exondys 51Injection50 mg/1mLIntravenousSarepta Therapeutics, Inc.2016-09-19Not applicableUS flag
Exondys 51Injection50 mg/1mLIntravenousSarepta Therapeutics, Inc.2016-09-19Not applicableUS flag

Categories

ATC Codes
M09AX06 — Eteplirsen
Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
AIW6036FAS
CAS number
1173755-55-9

References

General References
  1. Miceli MC, Nelson SF: The case for eteplirsen: Paving the way for precision medicine. Mol Genet Metab. 2016 Jun;118(2):70-1. doi: 10.1016/j.ymgme.2016.04.001. Epub 2016 Apr 14. [Article]
  2. Kole R, Krieg AM: Exon skipping therapy for Duchenne muscular dystrophy. Adv Drug Deliv Rev. 2015 Jun 29;87:104-7. doi: 10.1016/j.addr.2015.05.008. Epub 2015 May 14. [Article]
  3. Mendell JR, Rodino-Klapac LR, Sahenk Z, Roush K, Bird L, Lowes LP, Alfano L, Gomez AM, Lewis S, Kota J, Malik V, Shontz K, Walker CM, Flanigan KM, Corridore M, Kean JR, Allen HD, Shilling C, Melia KR, Sazani P, Saoud JB, Kaye EM: Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013 Nov;74(5):637-47. doi: 10.1002/ana.23982. Epub 2013 Sep 10. [Article]
KEGG Drug
D09900
PubChem Substance
347910319
RxNav
1810569
ChEMBL
CHEMBL2108278
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Eteplirsen
FDA label
Download (197 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentMuscular Dystrophy, Duchenne1
3CompletedTreatmentDuchenne's Muscular Dystrophy (DMD)1
2CompletedTreatmentDuchenne's Muscular Dystrophy (DMD)4
2CompletedTreatmentMuscular Dystrophy, Duchenne1
2Enrolling by InvitationTreatmentDuchenne's Muscular Dystrophy (DMD)2
1, 2CompletedTreatmentDuchenne's Muscular Dystrophy (DMD)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
InjectionIntravenous50 mg/1mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9018368No2015-04-282025-06-28US flag
US9416361No2016-08-162021-05-04US flag
US9506058No2016-11-292034-03-14US flag
US8486907No2013-07-162025-06-28US flag
US9243245No2016-01-262028-10-27US flag
US10364431No2019-07-302034-03-14US flag
US10337003No2019-07-022034-03-14US flag
USRE47751No2019-12-032025-06-28US flag
USRE47769No2019-12-172025-06-28US flag
US10533174No2001-05-042021-05-04US flag
US10781451No2005-06-282025-06-28US flag
USRE48468No2008-10-272028-10-27US flag

Properties

State
Solid
Experimental Properties
Not Available

Targets

Drugtargets
Accelerate your drug discovery research
with our fully connected ADMET & drug target dataset.
Learn more
Accelerate your drug discovery research with our ADMET & drug target dataset
Learn more
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Binding
References
  1. Mendell JR, Rodino-Klapac LR, Sahenk Z, Roush K, Bird L, Lowes LP, Alfano L, Gomez AM, Lewis S, Kota J, Malik V, Shontz K, Walker CM, Flanigan KM, Corridore M, Kean JR, Allen HD, Shilling C, Melia KR, Sazani P, Saoud JB, Kaye EM: Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013 Nov;74(5):637-47. doi: 10.1002/ana.23982. Epub 2013 Sep 10. [Article]

Drug created on November 18, 2007 18:29 / Updated on April 30, 2021 13:06