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.
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- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- 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)
Target Actions Organism ADMD-001 gene (exon 51 target site) bindingHumans - 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
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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
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Exondys 51 Injection 50 mg/1mL Intravenous Sarepta Therapeutics, Inc. 2016-09-19 Not applicable US 
Exondys 51 Injection 50 mg/1mL Intravenous Sarepta Therapeutics, Inc. 2016-09-19 Not applicable US
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
- 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]
- 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]
- 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]
- External Links
- KEGG Drug
- D09900
- PubChem Substance
- 347910319
- 1810569
- ChEMBL
- CHEMBL2108278
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Eteplirsen
- FDA label
- Download (197 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Muscular Dystrophy, Duchenne 1 3 Completed Treatment Duchenne's Muscular Dystrophy (DMD) 1 2 Completed Treatment Duchenne's Muscular Dystrophy (DMD) 4 2 Completed Treatment Muscular Dystrophy, Duchenne 1 2 Enrolling by Invitation Treatment Duchenne's Muscular Dystrophy (DMD) 2 1, 2 Completed Treatment Duchenne's Muscular Dystrophy (DMD) 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 50 mg/1mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9018368 No 2015-04-28 2025-06-28 US US9416361 No 2016-08-16 2021-05-04 US US9506058 No 2016-11-29 2034-03-14 US US8486907 No 2013-07-16 2025-06-28 US US9243245 No 2016-01-26 2028-10-27 US US10364431 No 2019-07-30 2034-03-14 US US10337003 No 2019-07-02 2034-03-14 US USRE47751 No 2019-12-03 2025-06-28 US USRE47769 No 2019-12-17 2025-06-28 US US10533174 No 2001-05-04 2021-05-04 US US10781451 No 2005-06-28 2025-06-28 US USRE48468 No 2008-10-27 2028-10-27 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
References
- 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