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eteplirsen (Exondys)
Indications:
- Duchenne muscular dystrophy (accelerated FDA approval)
Dosage:
- intravenous infusion 50 mg/mL (0.5-1 mL)
Pharmacokinetics:
- not metabolized
- renal elimination
- protein binding < 16%
Mechanism of action:
- targets mutations in a region implicated in 13% of Duchenne muscular dystrophy cases
- morpholino antisense oligomer triggering excision of exon 51 during pre-mRNA splicing of the dystrophin RNA transcript
- this changes the downstream reading frame of dystrophin
- eteplirsen given to a healthy person would result in a non-functional dystrophin protein
- for Duchenne muscular dystrophy patients with particular frameshifting mutations, eteplirsen can restore the mRNA reading frame resulting in a functional (albiet modified) dystrophin
General
oligonucleotide
metabolic agent (metabolic modifier)
References
- Wikipedia: Eteplirsen
https://en.wikipedia.org/wiki/Eteplirsen
- Cirak S, Arechavala-Gomeza V, Guglieri M et al
Exon skipping and dystrophin restoration in patients with
Duchenne muscular dystrophy after systemic phosphorodiamidate
morpholino oligomer treatment: an open-label, phase 2, dose-
escalation study.
Lancet. 2011 Aug 13;378(9791):595-605. Epub 2011 Jul 23.
PMID: 21784508 Free PMC Article
- FDA News Release. September 19, 2016
FDA grants accelerated approval to first drug for Duchenne
muscular dystrophy.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm
- Fiore K
Eteplirsen Boosts Dystrophin, Function in DMD -
Details from 12 patients in Study 201/202 reported at AAN.
MedPage Today. April 27, 2017
https://www.medpagetoday.com/MeetingCoverage/AAN/64874
- Mendell JR, et al
Exon skipping: Development and approval of eteplirsen for DMD
American Academy of Neurology (AAN) Annual Meeting 2017