Golodirsen

Golodirsen is designed to bind to exon 53 of dystrophin pre-mRNA resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. Exon 53 skipping is intended to allow for production of an internally truncated dystrophin protein in patients with genetic mutations that are amenable to exon 53 skipping [see Clinical Studies ( 14 )].

• VYONDYS 53 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with VYONDYS 53 [see Clinical Studies ( 14 )] .

• VYONDYS 53 is contraindicated in patients with a serious hypersensitivity reaction to golodirsen or to any of the inactive ingredients in VYONDYS 53. Anaphylaxis has occurred in patients receiving VYONDYS 53 [see Warnings and Precautions ( 5.1 )] .contraindicated

Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting VYONDYS 53 ( 2.1 ) 30 milligrams per kilogram once weekly ( 2.2 ) Administer as an intravenous infusion over 35 to 60 minutes via an in-line 0.2 micron filter ( 2.2 , 2.4 ) Dilution required prior to administration ( 2.3 ) 2.1 Monitoring to Assess Safety Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting VYONDYS 53. Consider measurement of glomerular filtration rate prior to initiation of VYONDYS 53. Monitoring for kidney toxicity during treatment is recommended. Obtain the urine samples prior to infusion of VYONDYS 53 or at least 48 hours after the most recent infusion [see Warnings and Precautions ( 5.2 )] . 2.2 Dosing Information The recommended dosage of VYONDYS 53 is 30 milligrams per kilogram administered once weekly as a 35 to 60-minute intravenous infusion via an in-line 0.2 micron filter. If a dose of VYONDYS 53 is missed, it may be administered as soon as possible after the scheduled dose. 2.3 Preparation Instructions VYONDYS 53 is supplied in single-dose vials as a preservative-free concentrated solution that requires dilution prior to administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Use aseptic technique. Calculate the total dose of VYONDYS 53 to be administered based on the patient's weight and the recommended dose of 30 milligrams per kilogram.

Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylaxis, rash, pyrexia, pruritus, urticaria, dermatitis, and skin exfoliation have occurred in patients who were treated with VYONDYS 53. If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion, interrupting or discontinuing the VYONDYS 53 therapy. ( 2.3 , 4 , 5.1 ) Kidney Toxicity: Based on animal data, may cause kidney toxicity. Kidney function should be monitored; creatinine may not be a reliable measure of renal function in DMD patients. ( 5.2 , 13.2 ) 5.1 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, rash, pyrexia, pruritus, urticaria, dermatitis, and skin exfoliation have occurred in VYONDYS 53-treated patients, some requiring treatment. If a hypersensitivity reaction occurs, institute appropriate medical treatment and consider slowing the infusion, interrupting, or discontinuing the VYONDYS 53 therapy and monitor until the condition resolves [see Dosage and Administration ( 2.4 )]. VYONDYS 53 is contraindicated in patients with a history of a serious hypersensitivity reaction to golodirsen or to any of the inactive ingredients in VYONDYS 53 [see Contraindications ( 4 )]. 5.2 Kidney Toxicity Kidney toxicity was observed in animals who received golodirsen [see Use in Specific Populations ( 8.4 )] .

The following serious adverse reactions are described below and elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] The most common adverse reactions (incidence ≥20% and higher than placebo) were headache, pyrexia, fall, abdominal pain, nasopharyngitis, cough, vomiting, and nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sarepta Therapeutics, Inc. at 1-888-SAREPTA (1-888-727-3782) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In the VYONDYS 53 clinical development program, 58 patients received at least one intravenous dose of VYONDYS 53, ranging between 4 mg/kg (0.13 times the recommended dosage) and 30 mg/kg (the recommended dosage). All patients were male and had genetically confirmed Duchenne muscular dystrophy. Age at study entry was 6 to 13 years. Most (86%) patients were Caucasian. VYONDYS 53 was studied in 2 double-blind, placebo-controlled studies. In Study 1 Part 1, patients were randomized to receive once-weekly intravenous infusions of VYONDYS 53 (n=8) in four increasing dose levels from 4 mg/kg to 30 mg/kg or placebo (n=4), for at least 2 weeks at each level.

8.1 Pregnancy Risk Summary There are no human or animal data available to assess the use of VYONDYS 53 during pregnancy. In the U.S. general population, major birth defects occur in 2 to 4% and miscarriage occurs in 15 to 20% of clinically recognized pregnancies. 8.2 Lactation Risk Summary There are no human or animal data to assess the effect of VYONDYS 53 on milk production, the presence of golodirsen in milk, or the effects of VYONDYS 53 on the breastfed infant. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for VYONDYS 53 and any potential adverse effects on the breastfed infant from VYONDYS 53 or from the underlying maternal condition. 8.4 Pediatric Use VYONDYS 53 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping, including pediatric patients [see Clinical Studies ( 14 )]. Intravenous administration of golodirsen (0, 100, 300, or 900 mg/kg) to juvenile male rats once weekly for 10 weeks (postnatal days 14 to 77) did not result in postnatal developmental (e.g., neurobehavioral, immune function, or male reproductive) toxicity. However, at the highest dose tested (900 mg/kg/week), golodirsen resulted in the death of animals because of renal impairment or failure.

Metabolism

The pharmacokinetics of golodirsen was evaluated in DMD patients following administration of intravenous doses ranging from 4 mg/kg/week to 30 mg/kg/week (i.e., recommended dosage). Golodirsen exposure increased proportionally with dose, with minimal accumulation with once-weekly dosing.

• Dec 12, 2019NDANDA211970Sarepta Theraps Inc

1. 1Product Dose Omission Issue13231%
2. 2No Adverse Event7317%
3. 3Poor Venous Access6315%
4. 4Intentional Dose Omission348.0%
5. 5Device Issue307.0%
6. 6Covid-19235.4%
7. 7Pyrexia184.2%
8. 8Malaise174.0%
9. 9Vomiting163.8%
10. 10Illness122.8%
11. 11Nausea112.6%
12. 12Pneumonia112.6%
13. 13Exposure To Sars-cov-2102.3%
14. 14Dehydration92.1%
15. 15Headache92.1%

The 6 most recently updated of 6 ClinicalTrials.gov registrations naming Golodirsen as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• An Open-Label Study of Golodirsen in Non-Ambulant Patients With Duchenne Muscular Dystrophy
  Terminated · Phase 4 · Interventional · 2 enrolled · Rare Disease Research, LLC
  NCT04708314updated 2026-04-03
• Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD)
  Completed · Phase 3 · Interventional · 228 enrolled · Sarepta Therapeutics, Inc.
  NCT02500381updated 2025-11-18
• A Long-term Observational Study Evaluating Eteplirsen, Golodirsen, or Casimersen in Routine Clinical Practice
  Enrolling by invitation · Observational · 300 enrolled · Sarepta Therapeutics, Inc.
  NCT06606340updated 2025-09-10
• An Extension Study to Evaluate Casimersen or Golodirsen in Patients With Duchenne Muscular Dystrophy
  Terminated · Phase 3 · Interventional · 171 enrolled · Sarepta Therapeutics, Inc.
  NCT03532542updated 2024-09-19
• A 48-Week, Open Label, Study to Evaluate the Efficacy and Safety of AMONDYS 45, EXONDYS 51, VYONDYS 53 in Subjects With DuchenneMuscular Dystrophy Carrying Eligible DMD Duplications.
  Completed · Phase 2 · Interventional · 3 enrolled · Kevin Flanigan
  NCT04179409updated 2023-10-26
• Phase I/II Study of SRP-4053 in DMD Patients
  Completed · Phase 1 · Phase 2 · Interventional · 39 enrolled · Sarepta Therapeutics, Inc.
  NCT02310906updated 2020-10-19

Frequently asked questions

How does Golodirsen work?

Golodirsen is designed to bind to exon 53 of dystrophin pre-mRNA resulting in exclusion of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. Exon 53 skipping is intended to allow for production of an internally truncated dystrophin protein in patients with genetic mutations that are amenable to exon 53 skipping [see Clinical Studies ( 14 )].

What is Golodirsen used for?

According to FDA labeling, Golodirsen carries indications including: VYONDYS 53 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. This indication is approved under accelerated approval based on an increase in dystrophin production in skeletal muscle observed in patients treated with VYONDYS 53 [see Clinical Studies ( 14 )] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Golodirsen?

Golodirsen is classified as Other drugs for disorders of the musculo-skeletal system, Antisense Oligonucleotide, Increased Protein Synthesis.

What are the brand names for Golodirsen?

Golodirsen is marketed under brand names including Vyondys 53.

What are the contraindications for Golodirsen?

Golodirsen labeling lists contraindications including: VYONDYS 53 is contraindicated in patients with a serious hypersensitivity reaction to golodirsen or to any of the inactive ingredients in VYONDYS 53. Anaphylaxis has occurred in patients receiving VYONDYS 53 [see Warnings and Precautions ( 5.1 )] .. Always consult the full prescribing information and a clinician.