 | |
| Clinical data | |
|---|---|
| Trade names | Vyondys 53 |
| Other names | SRP-4053 |
| AHFS/Drugs.com | Monograph |
| License data | |
| Routes of administration | Intravenous |
| Drug class | Antisense oligonucleotide |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
| CAS Number | |
| DrugBank | |
| UNII | |
| KEGG | |
| Chemical and physical data | |
| Formula | C305H481N138O112P25 |
| Molar mass | 8647.401 g·mol−1 |
Golodirsen, sold under the brand nameVyondys 53, is amedication used for the treatment ofDuchenne muscular dystrophy.[2] It is anantisense oligonucleotide medication ofphosphorodiamidatemorpholinooligomer (PMO)chemistry.[1][3]
The most common side effects includeheadache,fever, fall,cough,vomiting,abdominal pain, cold symptoms (nasopharyngitis) andnausea.[2][1]
Golodirsen isindicated for the treatment of Duchenne muscular dystrophy in people who have a confirmedmutation of thedystrophin gene that is amenable toexon 53 skipping.[2][1]
Golodirsen has been provisionally approved for approximately 8% of all people with Duchenne muscular dystrophy amenable to exon 53 skipping.[3] It works by inducingexon skipping in the dystrophin gene and thereby increasing the amount of dystrophin protein available to muscle fibers.[3]
The most common side effects includeheadache,fever, fall,cough,vomiting,abdominal pain, cold symptoms (nasopharyngitis) andnausea.[2][1] In animal studies, no significant changes were seen in themale reproductive system ofmonkeys andmice following weeklysubcutaneous administration.[3] According to the reports obtained from theclinical trials,pain at the site ofintravenous administration,back pain,oropharyngealpain,sprain inligaments,diarrhea,dizziness,contusion,flu,earinfection,rhinitis,skinabrasion,tachycardia, andconstipation occurred at an elevated frequency in the treatment group, as compared to theirplacebo counterparts.[3] Hypersensitivity reactions, including rash, fever, itching, hives, skin irritation (dermatitis) and skin peeling (exfoliation), have occurred in people who were treated with golodirsen.[2]
Renal toxicity was observed in animals who received golodirsen.[2][4] Althoughrenaltoxicity was not observed in the clinical studies with golodirsen, potentially fatalglomerulonephritis, has been observed after administration of someantisense oligonucleotides.[2] Renal function should be monitored in those taking golodirsen.[2][5][6]
Following single or multiple intravenous infusions, the majority ofdrug elimination occurs within 24 hours of intravenous administration. The elimination half-life of golodirsen, in parity witheteplirsen was 3 to 6 hours.[3]
As a first-generationmedication, golodirsen is far away from being curative;clinical trial outcomes have demonstrated it to have a marginal effect on ameliorating Duchenne muscular dystrophypathology.[3] As of December 2019, golodirsen is approved fortherapeutic use in the United States, as well as in the countries that automatically recognize the decisions of the USFood and Drug Administration, under the condition that its benefit will be demonstrated in aconfirmatory clinical trial.
Golodirsen is one of the very few FDA-approvedexon-skippingtherapy for Duchenne muscular dystrophy, although the clinical benefits of the medication are yet to established.[1][3] While the development of golodirsen needed huge financing, it is only applicable to a small subset of people with Duchenne muscular dystrophy.[citation needed]Sarepta Therapeutics has announced that golodirsen will cost in parity witheteplirsen, another medication of a similar kind, which may be as high asUS$300,000 per year.[citation needed] Also, the accelerated approval of golodirsen has paved the way for people to have early access to the medication, at the same time, it is shrouded withcontroversy over a number of issues.[3] A double-blind placebo-controlled confirmatory trial (NCT02500381) is ongoing to resolve the issues.[citation needed]
Golodirsen was developed by collaborative research led by Prof. Steve Wilton and Prof.Sue Fletcher in the Perron Institute and licensed toSarepta Therapeutics by theUniversity of Western Australia.[3]
In the 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.[2] The change was asurrogate endpoint and the trial did not establish clinical benefit of the drug, including changes to the subject'smotor function.[2]
Thepharmacological assessment of golodirsen did not include special population groups, e.g.,pregnant andlactatingwomen, the elderly, and people with concurrent disease states.[medical citation needed] AsDMD predominantly affectsmalechildren andyoungadults, and golodirsen is indicated for thetreatment of children, but primarily not foradultwomen, the elderly, and people withcomorbidity, it was not evaluated on them.[3]
The USFood and Drug Administration (FDA) approved golodirsen in December 2019,[2][7][8] under theaccelerated approval pathway.[2] The application for golodirsen was grantedfast track,priority review, andorphan drug designations, and a rare pediatric disease priority review voucher.[2]
This article incorporates text from this source, which is in thepublic domain. This article incorporates text from this source, which is in thepublic domain.