Casimersen Explained

Width:300
Tradename:Amondys 45
Dailymedid:Casimersen
Routes Of Administration:Intravenous
Class:Antisense oligonucleotide
Atc Prefix:M09
Atc Suffix:AX13
Legal Us:Rx-only
Legal Us Comment:[1]
Cas Number:1422958-19-7
Drugbank:DB14984
Unii:X8UHF7SX0R
Kegg:D11988
Synonyms:SRP-4045
C:268
H:424
N:124
O:95
P:22

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.[2] [3] [4] It is an antisense oligonucleotide of phosphorodiamidate morpholino oligomer (PMO). Duchenne muscular dystrophy is a rare disease that primarily affects boys. It is caused by low levels of a muscle protein called dystrophin. The lack of dystrophin causes progressive muscle weakness and premature death.

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

Casimersen was approved for medical use in the United States in February 2021,[5] 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.

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.

Adverse effects

Common side effects include: headache, fever, joint pain, cough and cold symptoms.[6]

Pharmacology

Pharmacodynamics

Duchenne muscular dystrophy is an X-linked recessive disorder that results in the absence of a functional dystrophin protein.[7] 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 dystrophin protein.

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. 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. 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. The trial was conducted at seven sites in five countries (United States, Canada, Germany, Spain, Czech Republic).[8]

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

External links

Notes and References

  1. Web site: Amondys 45- casimersen injection . DailyMed . 1 March 2021.
  2. FDA Approves Targeted Treatment for Rare Duchenne Muscular Dystrophy Mutation . U.S. Food and Drug Administration (FDA) . 25 February 2021 . 25 February 2021.
  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 . Sarepta Therapeutics . GlobeNewswire . 25 February 2021 . 25 February 2021.
  4. Book: Toshifumi Yokota . Rodrigues M, Yokota T . Exon Skipping and Inclusion Therapies . An Overview of Recent Advances and Clinical Applications of Exon Skipping and Splice Modulation for Muscular Dystrophy and Various Genetic Diseases . Methods in Molecular Biology . Clifton, N.J. . 1828 . 31–55 . 2018 . 30171533 . 10.1007/978-1-4939-8651-4_2 . 978-1-4939-8650-7 .
  5. Web site: Drug Approval Package: Amondys 45 . U.S. Food and Drug Administration (FDA) . 18 March 2021 . 13 September 2021.
  6. Web site: Casimersen Uses, Side Effects & Warnings . 13 May 2022 . Drugs.com .
  7. Web site: Casimersen . 6 May 2022 . Drugbank.
  8. Web site: Drug Trial Snapshot: Amondys 45 . U.S. Food and Drug Administration (FDA) . 2 December 2022 . 2 December 2022.
  9. Web site: Casimersen Orphan Drug Designations and Approvals . U.S. Food and Drug Administration (FDA) . 4 June 2019 . 25 February 2021.
  10. Advancing Health Through Innovation: New Drug Therapy Approvals 2021 . U.S. Food and Drug Administration (FDA) . 13 May 2022 . PDF . 22 January 2023 . 6 December 2022 . https://web.archive.org/web/20221206210020/https://www.fda.gov/media/155227/download . live .