Golodirsen

Golodirsen, sold under the brand name Vyondys 53, is a 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 53 skipping.[3] Golodirsen is an antisense oligonucleotide.[2]

Golodirsen
Clinical data
Trade namesVyondys 53
Other namesSRP-4053
AHFS/Drugs.comMonograph
License data
Pregnancy
category
  • US: N (Not classified yet) [1]
    Routes of
    administration    		Intravenous
    Drug classAntisense oligonucleotide
    ATC code
    • None
    Legal status
    Legal status
    Identifiers
    CAS Number
    DrugBank
    UNII
    KEGG
    Chemical and physical data
    FormulaC305H481N138O112P25
    Molar mass8647.401 g·mol−1

    The drug was developed by Sarepta Therapeutics. It works by inducing exon skipping in the dystrophin gene and thereby increasing the amount of dystrophin protein available to muscle fibers.[4][5]

    The most common side effects include headache, fever, fall, cough, vomiting, abdominal pain, cold symptoms (nasopharyngitis) and nausea.[3][2]

    No clinical benefit of using golodirsen has been established. As of December 2019, golodirsen is approved for therapeutic use in the United States, as well as in the countries that automatically recognize the decisions of the US Food and Drug Administration, under the condition that its benefit will be demonstrated in a confirmatory clinical trial.

    Medical uses

    Golodirsen 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 53 skipping.[3][2]

    Pharmacokinetics and toxicity

    In the pivotal clinical trial of golodirsen, dystrophin levels increased, on average, from 0.10% of normal at baseline to 1.02% of normal after 48 weeks of treatment with the drug or longer.[3] The change was a surrogate endpoint and the trial did not establish clinical benefit of the drug, including changes to subject's motor function.[3]

    The most common side effects reported by participants receiving golodirsen in clinical studies were headache, fever (pyrexia), cough, vomiting, abdominal pain, cold symptoms (nasopharyngitis) and nausea.[3] Hypersensitivity reactions, including rash, fever, itching, hives, skin irritation (dermatitis) and skin peeling (exfoliation), have occurred in people who were treated with golodirsen.[3]

    Renal toxicity was observed in animals who received golodirsen.[3][6] Although renal toxicity was not observed in the clinical studies with golodirsen, renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides.[3] Renal function should be monitored in those taking golodirsen.[3][7][8]

    History

    The U.S. Food and Drug Administration (FDA) approved golodirsen in December 2019,[3][9][10] under the accelerated approval pathway.[3] The application for golodirsen was granted fast track designation, priority review designation, orphan drug designation, and a rare pediatric disease priority review voucher.[3]

    References
    1. "Golodirsen (Vyondys 53) Use During Pregnancy". Drugs.com. 18 February 2020. Retrieved 6 August 2020.
    2. "Vyondys 53- golodirsen injection". DailyMed. 31 March 2020. Retrieved 6 August 2020.
    3. "FDA grants accelerated approval to first targeted treatment for rare Duchenne muscular dystrophy mutation". U.S. Food and Drug Administration (FDA) (Press release). 12 December 2019. Archived from the original on 13 December 2019. Retrieved 12 December 2019. This article incorporates text from this source, which is in the public domain.
    4. Aslesh T, Maruyama R, Yokota T (January 2018). "Skipping Multiple Exons to Treat DMD-Promises and Challenges". Biomedicines. 6 (1): 1. doi:10.3390/biomedicines6010001. ISSN 2227-9059. PMC 5874658. PMID 29301272.
    5. Lim KR, Yokota T (2018). "Quantitative Evaluation of Exon Skipping in Immortalized Muscle Cells In Vitro". Methods Mol. Biol. 1828: 127–39. doi:10.1007/978-1-4939-8651-4_7. PMID 30171538.
    6. "Safety risks highlighted in FDA letter on Sarepta's Vyondys". BioPharma Dive. 22 January 2020. Retrieved 22 January 2020.
    7. Terry, Mark (22 January 2020). "FDA Publishes Initial Rejection Letter of Sarepta's Vyondys 53 for DMD". BioSpace. Retrieved 22 January 2020.
    8. Unger EF (19 August 2019). "NDA 211970 Other action letter" (PDF). U.S. Food and Drug Administration (FDA). Retrieved 22 January 2020.
    9. "Drug Approval Package: Vyondys 53 (golodirsen)". U.S. Food and Drug Administration (FDA). 21 January 2020. Retrieved 22 January 2020.
    10. "Drug Trials Snapshots: Vyondys 53". U.S. Food and Drug Administration (FDA). 12 December 2019. Retrieved 24 January 2020. This article incorporates text from this source, which is in the public domain.
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