Casimersen

Casimersen, sold under the brand name Amondys 45, is an antisense oligonucleotide medication used for the treatment of Duchenne muscular dystrophy (DMD) in people who have a confirmed mutation of the dystrophin gene that is amenable to exon 45 skipping.[1][2][3][4] It is an antisense oligonucleotide of phosphorodiamidate morpholino oligomer (PMO).[1] Duchenne muscular dystrophy is a rare disease that primarily affects boys.[5] It is caused by low levels of a muscle protein called dystrophin.[5] The lack of dystrophin causes progressive muscle weakness and premature death.[5]

Casimersen
Clinical data
Trade namesAmondys 45
Other namesSRP-4045
AHFS/Drugs.comMonograph
License data
Routes of
administration		Intravenous
Drug classAntisense oligonucleotide
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
FormulaC268H424N124O95P22
Molar mass7584.536 g·mol−1

The most common side effects include upper respiratory tract infections, cough, fever, headache, joint pain and throat pain.[2][5]

Casimersen was approved for medical use in the United States in February 2021,[1][2][6] and it is the first FDA-approved targeted treatment for people who have a confirmed mutation of the DMD gene that is amenable to skipping exon 45.[2]

Medical uses

Casimersen is indicated for the treatment of Duchenne muscular dystrophy (DMD) in people who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping.[1][2]

Adverse effects

Common side effects include: headache, fever, joint pain, cough and cold symptoms.[7]

Pharmacology

Pharmacodynamics

Duchenne muscular dystrophy is an X-linked recessive disorder that results in the absence of a functional dystrophin protein.[8] Dystrophin protein is a protein that consists of an N-terminal actin-binding domain, C-terminal B-dystroglycan- binding domain, and 24 internal spectrum-like repeats. Dystrophin plays a role in muscle function and without dystrophin, muscle tissue will be replaced with fibrous and adipose tissue. Casimersen is an antisense phosphorodiamidate morpholino oligonucleotide designed to bind to the exon 45 of the DMD pre-MRNA, which prevents its exclusion into the mature RNA before translation. This change causes the production of an internally truncated dysphotrophin protein.[8]

History

Casimersen was evaluated in a double-blind, placebo-controlled study in which 43 participants were randomized 2:1 to receive either intravenous casimersen or placebo.[2] All participants were male, between 7 and 20 years of age, and had a genetically confirmed mutation of the DMD gene that is amenable to exon 45 skipping.[2] The benefit was evaluated by measuring the level of dystrophin in muscle biopsies in 43 participants before treatment and at week 48, in an interim analysis.[5] The trial was conducted at seven sites in five countries (United States, Canada, Germany, Spain, Czech Republic).[5]

The U.S. Food and Drug Administration (FDA) granted the application for casimersen fast track, priority review, and orphan drug designations.[2][9][10] The FDA granted the approval of Amondys 45 to Sarepta Therapeutics, Inc.[2]

References
  1. "Amondys 45- casimersen injection". DailyMed. Retrieved 1 March 2021.
  2. "FDA Approves Targeted Treatment for Rare Duchenne Muscular Dystrophy Mutation". U.S. Food and Drug Administration (FDA) (Press release). 25 February 2021. Retrieved 25 February 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  3. "Sarepta Therapeutics Announces FDA Approval of Amondys 45 (casimersen) Injection for the Treatment of Duchenne Muscular Dystrophy (DMD) in Patients Amenable to Skipping Exon 45" (Press release). Sarepta Therapeutics. 25 February 2021. Retrieved 25 February 2021 – via GlobeNewswire.
  4. Rodrigues M, Yokota T (2018). "An Overview of Recent Advances and Clinical Applications of Exon Skipping and Splice Modulation for Muscular Dystrophy and Various Genetic Diseases". Exon Skipping and Inclusion Therapies. Methods in Molecular Biology. Vol. 1828. Clifton, N.J. pp. 31–55. doi:10.1007/978-1-4939-8651-4_2. ISBN 978-1-4939-8650-7. PMID 30171533.{{cite book}}: CS1 maint: location missing publisher (link)
  5. "Drug Trial Snapshot: Amondys 45". U.S. Food and Drug Administration (FDA). 2 December 2022. Retrieved 2 December 2022. Public Domain This article incorporates text from this source, which is in the public domain.
  6. "Drug Approval Package: Amondys 45". U.S. Food and Drug Administration (FDA). 18 March 2021. Retrieved 13 September 2021.
  7. "Casimersen Uses, Side Effects & Warnings". Drugs.com. Retrieved 13 May 2022.
  8. "Casimersen". Drugbank. Retrieved 6 May 2022.
  9. "Casimersen Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 4 June 2019. Retrieved 25 February 2021.
  10. Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (PDF). U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. Archived from the original on 6 December 2022. Retrieved 22 January 2023. Public Domain This article incorporates text from this source, which is in the public domain.
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