Vyondys 53

Vyondys 53 is used to treat Duchenne muscular dystrophy (DMD) in people who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. It is an exon-skipping treatment given once a week as an intravenous infusion by a healthcare provider.

• Vyondys and Vyondys 53 are the same medicine. Vyondys is just a shortened name. They are both names for golodirsen injection.
• Your healthcare provider will arrange a genetic test to confirm whether you or your child has a DMD gene mutation that is amenable to exon 53 skipping. Vyondys 53 only works for this group.

Vyondys 53 (golodirsen) gained FDA approval on December 12, 2019, under accelerated approval. This was based on an increase in dystrophin production in skeletal muscle, not on an improvement in symptoms or function. Continued approval may be contingent upon verification of a clinical benefit in confirmatory trials.

Not yet. Vyondys 53 was approved on the basis of a laboratory measure, the amount of dystrophin protein in muscle, rather than on evidence that it improves how people with DMD move or feel. This is what accelerated approval means.

The confirmatory trial, called ESSENCE, reported results in March 2026. It enrolled 225 patients aged 6 to 13 and did not meet its primary endpoint. The difference between Vyondys 53 and placebo in the time taken to climb four steps at 96 weeks was 0.06 steps per second, which was not statistically significant (p=0.309). In an analysis that excluded roughly 10% of participants whose baseline assessments were affected by COVID-19, the difference was 0.12 steps per second (p=0.050). No new safety concerns were identified, and most side effects were mild (88%) or moderate (10.9%).

Sarepta Therapeutics has asked the FDA to convert Vyondys 53 from accelerated approval to traditional approval, using the ESSENCE data together with real-world evidence. The FDA accepted the application for review on June 30, 2026, with a target decision date of February 28, 2027. Vyondys 53 remains FDA-approved and available while this review is underway.

Golodirsen is designed to bind to exon 53 of dystrophin pre-mRNA, so that this section is left out when the genetic message is processed. Skipping exon 53 is intended to let cells join other exons together and produce a dystrophin protein that is shorter than normal but may still have some function.

Dystrophin is a protein needed to keep muscle cells intact. People with DMD have a mutation in the gene that codes for dystrophin, which means they cannot make enough working copies of it. Without it, muscle cells become damaged and weaken over time.

Golodirsen is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass. It contains 25 linked subunits.

What the dystrophin results showed

In the study that supported approval, all 25 patients who were assessed had an increase in exon 53 skipping after treatment, confirmed by testing muscle biopsy samples.

Dystrophin levels are measured as a percentage of the level found in people without DMD. Average levels rose from 0.10% of normal before treatment to 1.02% of normal after 48 weeks, an average increase of 0.92% of normal (p<0.001). The median increase was 0.88%. Results varied widely between individuals, from almost no change to an increase of around 4%.

These remain small amounts of dystrophin in absolute terms, and it is not known what level is needed to change the course of the disease. Dystrophin measurements can also be affected by how samples are processed and which laboratory method is used, so results from different tests cannot be compared directly.

Vyondys 53 is given as an infusion into a vein once a week by a healthcare provider. It must be diluted before it is given.

• A numbing cream may be applied to the infusion site beforehand if needed.
• The infusion is given slowly, over 35 to 60 minutes, through an in-line 0.2 micron filter.
• The IV line is flushed with sodium chloride 0.9% before and after the infusion.
• No other medicines are mixed with Vyondys 53 or given through the same IV line at the same time.

If a hypersensitivity reaction happens during the infusion, it may be slowed, interrupted, or stopped.

Do not administer Vyondys 53 to anyone who has had a serious hypersensitivity reaction to golodirsen or to any of the inactive ingredients in Vyondys 53.

Before receiving Vyondys 53, tell your healthcare provider if you:

• have or have had kidney problems
• have had an allergic reaction to Vyondys 53, golodirsen, or any of the inactive ingredients in the injection
• are pregnant or intending to become pregnant
• are breastfeeding or intend to breastfeed.

Kidney monitoring before and during treatment

Because reduced muscle mass affects creatinine readings, creatinine is not a reliable measure of kidney function in people with DMD. Different tests are used instead.

• Before starting Vyondys 53: serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio. Measuring glomerular filtration rate may also be considered.
• During treatment: urine dipstick every month, and serum cystatin C and urine protein-to-creatinine ratio every 3 months.
• Urine samples need to be collected either just before an infusion or at least 48 hours after the last one, because golodirsen in the urine can affect the result. Some laboratory tests use a reagent called pyrogallol red that can give a false positive for protein in the urine, so an alternative test may be used.
• If serum cystatin C stays raised or protein in the urine persists, referral to a pediatric kidney specialist is recommended.

Pregnancy

There are no human or animal data on the use of Vyondys 53 during pregnancy, so its effects are not known. For context, in the general US population major birth defects occur in 2% to 4% and miscarriage occurs in 15% to 20% of recognized pregnancies.

Breastfeeding

There are no human or animal data on whether golodirsen passes into breast milk, whether it affects milk production, or how it might affect a breastfed baby. The benefits of breastfeeding should be weighed against your need for Vyondys 53 and any possible effects on your baby.

Use in specific groups

Vyondys 53 has not been studied in female patients. There is no experience with its use in people aged 65 years or older, because DMD is largely a disease of children and young adults.

In people with reduced kidney function, golodirsen is cleared more slowly. However, because creatinine-based estimates of kidney function are unreliable in DMD, no specific dose change can be recommended. Anyone with known kidney problems should be monitored closely during treatment.

Most common side effects

The table below shows side effects reported by at least 20% of people treated with Vyondys 53 in two placebo-controlled studies, alongside the rate in people given placebo.

Other side effects

The following occurred in more than 5% of people treated with Vyondys 53 and more often than with placebo:

• pain at the administration site, or a reaction related to the IV catheter site
• back pain, mouth or throat pain, or general pain
• diarrhea or constipation
• dizziness
• flu, stuffy or runny nose, ear infection, seasonal allergy
• bruising, skin scrapes, ligament sprains, broken bones
• fast heartbeat (tachycardia).

Serious side effects and warnings

Hypersensitivity reactions. Hypersensitivity reactions have occurred in people treated with Vyondys 53, and some needed treatment. These include anaphylaxis, rash, fever, itching, hives, dermatitis, and peeling skin. Anaphylaxis has also been reported since Vyondys 53 came into use. If a reaction happens, your healthcare provider will give appropriate treatment and may slow, interrupt, or stop the infusion, and will monitor you until it settles. Get emergency medical help if you have signs of an allergic reaction: hives, itching, rash, blistering or peeling skin, fever, difficulty breathing, or swelling of your face, lips, tongue, or throat.

Kidney toxicity. Kidney toxicity was seen in animals given golodirsen. It was not seen in the clinical studies of Vyondys 53, but experience with the medicine is limited, and kidney toxicity, including glomerulonephritis that can be fatal, has been seen with some other antisense oligonucleotides. For this reason your kidney function will be monitored throughout treatment. Tell your healthcare provider if you notice pink, brown, or red urine, foamy urine, or swelling in your face, hands, feet, or stomach.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Check serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio before starting Vyondys 53.

• Usual dosage: 30 mg per kg of body weight, once weekly, as an intravenous infusion.
• Infuse over 35 to 60 minutes through an in-line 0.2 micron filter.
• Dilution in sodium chloride 0.9% to a total volume of 100 to 150 mL is required before administration.

The dose is the same regardless of age or kidney function. It is adjusted only for body weight.

If a dose of Vyondys 53 is missed, it may be given as soon as possible after the scheduled dose. Contact your infusion clinic or healthcare provider to rearrange the appointment.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Based on laboratory studies, golodirsen has a low potential for interactions with other medicines. It did not block the main liver enzymes that process drugs (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4/5), and it was only a weak inducer of CYP1A2. It is not broken down by liver enzymes, and it is not a substrate or strong inhibitor of the major drug transporters that were tested.

Even so, tell your doctor about all your current medicines, including prescription and over-the-counter medicines, vitamins, and herbal products, and about any medicine you start or stop using.

Golodirsen is cleared quickly. Its elimination half-life is about 3.4 hours, and it is mostly passed out unchanged in the urine. It is not broken down into other substances, and between 33% and 39% of it binds to proteins in the blood. Levels rise in proportion to the dose, with little build-up from one weekly dose to the next.

Vyondys 53 is stored and handled by your healthcare provider.

• Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze.
• Keep vials in the original carton until ready for use, to protect from light.
• Vyondys 53 contains no preservative. Once diluted, the infusion should be given straight away and completed within 4 hours. If that is not possible, the diluted solution may be kept for up to 24 hours at 2°C to 8 °C.
• Any unused Vyondys 53 is discarded.

Active ingredient: golodirsen 100 mg per 2 mL vial (50 mg/mL).

Inactive ingredients: each milliliter contains 0.2 mg potassium chloride, 0.2 mg potassium phosphate monobasic, 8 mg sodium chloride, and 1.14 mg sodium phosphate dibasic, anhydrous, in water for injection. It may contain hydrochloric acid or sodium hydroxide to adjust pH.

Vyondys 53 is an isotonic phosphate-buffered saline solution with an osmolality of 260 to 320 mOsm and a pH of 7.5. It is a clear to slightly opalescent, colorless liquid, and may contain trace amounts of small, white to off-white particles. It is supplied in 100 mg/2 mL (50 mg/mL) single-dose vials.

Vyondys 53 is manufactured for Sarepta Therapeutics, Inc., based in Cambridge, Massachusetts, USA. Sarepta Therapeutics develops RNA-targeted therapeutics, with a focus on rare diseases, particularly Duchenne muscular dystrophy.