Vyondys 53 (Golodirsen)

Vyondys 53 (golodirsen, SRP-4053) is an approved exon-skipping therapy developed by Sarepta Therapeutics to treat Duchenne muscular dystrophy (DMD) patients whose disease is amenable to exon 53 skipping.

Exon skipping addresses the underlying cause of DMD by promoting the production of a shorter, but still functional, dystrophin protein to stabilize or slow disease progression.

Sarepta Therapeutics applied to the U.S. Food and Drug Administration (FDA) for the approval of Vyondys 53 and received a Complete Response Letter in August of 2019, rejecting approval of the drug.  The letter stated concerns of possible infection at the injection sites and renal (kidney) toxicity that was seen in preclinical (animal) studies. The toxicity in those studies was observed at dosage levels ten-times what is being used in clinical trials. No toxicity was observed in the clinical trial used for the drug application. 

Sarepta filed an appeal and after meeting with the FDA, the FDA reversed its decision and gave Vyondys 53 accelerated approval in December of 2019.

How Vyondys 53 works

DMD is caused by a mutation or error in the DMD gene, which encodes for dystrophin, an essential protein involved in muscle cell integrity. Without dystrophin, the muscle’s integrity is lost and it becomes easily damaged during normal activity.

Exons are the sections of a DNA or RNA molecule that contain coding information for a set of amino acids, the building blocks of proteins. The exons are decoded sequentially to synthesize a protein. Some cases of DMD are caused by the deletion of certain exons, disturbing the alignment of the neighboring exons and interfering with the genetic code. The interruption in the code hinders protein production, resulting in no dystrophin protein being produced by the cells. 

Vyondys 53is designed to mask exon 53 in the mRNA (a temporary copy of a gene used to make a protein) of the DMD gene so the protein synthesis machinery can skip this exon and piece together the remaining exons to make a smaller, but functional, dystrophin protein.

Approximately 8% of boys with DMD may be amenable to exon 53 skipping.

Vyondys 53 in clinical trials

A Phase 1/2 clinical trial (NCT02310906) assessed the safety, tolerability, efficacy, and pharmacokinetics (movement in the body) of Vyondys 53 in 25 DMD boys with deletions amenable to exon 53 skipping. Participants received weekly infusions of 30 mg per kg of bodyweight of Vyondys 53 for at least 48 weeks. Muscle biopsies were performed before and after 48 weeks of treatment. Results showed a marked increase in functional dystrophin following Vyondys 53 treatment. Sarepta Therapeutics’ application to the FDA to review Vyondys 53 for approval is supported by these findings.

A Phase 3 study called ESSENCE (NCT02500381) initiated in 2016 is still recruiting DMD patients to evaluate the effectiveness of Vyondys 53 and Casimersen (SRP-4045), another exon-skipping therapy, compared to placebo. Boys, ages 7 to 13, with mutations amenable to exon 53 and exon 45 skipping are being enrolled at multiple sites across several countries, including the U.S., Canada, Australia, Israel, and Europe. Interim results showed a significant mean increase in dystrophin protein in the Casimersen-treated group. Results about Vyondys 53-treated patients are not yet available. The trial is expected to conclude in May 2023.

A Phase 3 extension study (NCT03532542) is underway to evaluate the long-term safety and tolerability of Vyondys 53 and Casimersen in DMD patients who have been treated previously with these exon-skipping treatments in a clinical trial setting. A total of 260 DMD boys, ages 7 to 13 will be invited to participate in this study. Boys with mutations amenable to exon 53 skipping will be included in the Vyondys 53 treatment group, while those with mutations that can benefit from exon 45 skipping will be treated with Casimersen. Patients will receive weekly intravenous infusions of treatment for up to 144 weeks, and the number of severe adverse events (side effects) will be assessed.


Last updated: Dec. 13, 2019


Muscular Dystrophy News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare providers with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.