Golodirsen (Monograph)

Brand name: Vyondys 53
Drug class: Antisense Oligonucleotides
Chemical name: all-P-ambo-[2′,3′-Azanediyl-P-(dimethylamino)-P,2′,3′-trideoxy-2′,3′-seco](2′-N→5′)(G-T-T-G-C-C-T-C-C-G-G-T-T-C-T-G-A-A-G-G-T-G-T-T-C) 5′-{P-[4-({2-[2-(2-hydroxyethoxy)ethoxy]ethoxy}carbonyl)piperazin-1-yl]-N,N-dimethylphosphonamidate}
Molecular formula: C₃₀₅H₄₈₁N₁₃₈O₁₁₂P₂₅
CAS number: 1422959-91-8

Medically reviewed by Drugs.com on Apr 16, 2025. Written by ASHP.

Introduction

Antisense oligonucleotide that binds to exon 53 of dystrophin premessenger RNA (pre-mRNA).

Uses for Golodirsen

Duchenne Muscular Dystrophy

Management of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation of the dystrophin gene that is amenable to skipping of exon 53 (designated an orphan drug by FDA for use in this condition).

Accelerated approval based on increased dystrophin production (a surrogate marker of response). Continued approval may be contingent on verification of clinical benefit in confirmatory studies.

Approximately 7.7–10.1% of patients with DMD have specific mutations of the dystrophin gene amenable to exon 53 skipping.

Golodirsen Dosage and Administration

General

Measure GFR by 24-hour urine collection prior to initiation of therapy. Monitor for renal toxicity during therapy. (See Renal Impairment under Cautions.)

Administration

Administer by IV infusion using an inline 0.2-µm filter.

IV Administration

For solution compatibility information, see Compatibility under Stability.

Consider pretreatment of the infusion site with topical anesthetic cream.

Do not mix or administer simultaneously with other drugs. Flush IV line with 0.9% sodium chloride injection before and after infusion.

If a dose is missed, administer missed dose as soon as possible.

Vials are for single use only; discard unused portions since the injection concentrate contains no preservatives.

Dilution

Must dilute injection concentrate prior to IV infusion.

Visually inspect vials. The injection concentrate should be a clear to slightly opalescent and colorless solution that may contain trace amounts of small, white to off-white amorphous particles.

Determine number of vials needed based on patient’s body weight and recommended dose. Allow vials to warm to room temperature. Mix contents by gently inverting vials 2–3 times; do not shake.

Withdraw appropriate volume of injection concentrate from appropriate number of vials using a syringe with a 21-gauge or smaller noncoring needle and dilute with 0.9% sodium chloride injection to a total volume of 100–150 mL.

Visually inspect diluted solution; do not use if it is cloudy, discolored, or contains extraneous particulate matter other than trace amounts of small, white to off-white amorphous particles.

Administer immediately after dilution, completing administration within 4 hours. If immediate administration is not possible, may store diluted solution at 2–8°C for ≤24 hours. Do not freeze.

Rate of Administration

Infuse IV over 35–60 minutes. If hypersensitivity reaction occurs, consider slowing infusion or interrupting therapy. (See Sensitivity Reactions under Cautions.)

Dosage

Pediatric Patients

Duchenne Muscular Dystrophy

IV

30 mg/kg once weekly.

Adults

Duchenne Muscular Dystrophy

IV

30 mg/kg once weekly.

Special Populations

Hepatic Impairment

No specific dosage adjustments can be recommended.

Renal Impairment

No special dosage recommendations at this time based on GFR. (See Renal Impairment under Cautions.)

Geriatric Patients

No special dosage recommendations at this time. (See Geriatric Use under Cautions.)

Cautions for Golodirsen

Contraindications

None.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions (e.g., rash, pyrexia, pruritus, urticaria, dermatitis, skin exfoliation) reported.

If hypersensitivity reaction occurs, initiate appropriate medical treatment and consider slowing or interrupting infusion.

Renal Toxicity

May cause renal toxicity based on animal studies. Although not observed in clinical studies of golodirsen, renal toxicity, including potentially fatal glomerulonephritis, observed following administration of other antisense oligonucleotides.

Monitor renal function during therapy. Measure GFR by 24-hour urine collection prior to initiating therapy. Because reduced skeletal muscle mass can affect S_cr measurements, S_cr may not be a reliable marker of renal function in patients with DMD.

During golodirsen therapy, monitor for proteinuria with dipstick urinalysis monthly and measure serum cystatin C every 3 months. In patients with confirmed urine dipstick result of 2+ or greater or elevated serum cystatin C concentration, perform a 24-hour urine collection to quantify proteinuria and assess GFR.

Specific Populations

Pregnancy

Not studied in female patients. Not known whether golodirsen is associated with risk if used during pregnancy.

Lactation

Not studied in female patients. Not known whether golodirsen is distributed into milk, affects milk production, or affects the breast-fed infant.

Consider known benefits of breast-feeding along with the mother's clinical need for golodirsen and any potential adverse effects on the drug or disease on the infant.

Pediatric Use

Golodirsen is labeled for use in certain pediatric patients with DMD. (See Uses.)

In juvenile animal studies, mortality attributed to renal impairment or failure observed. (See Renal Toxicity under Cautions.) No evidence of developmental toxicity (e.g., male reproductive system, neurobehavioral development, immune function) observed.

Geriatric Use

No experience in geriatric patients; DMD is generally a disease of children and young adults.

Hepatic Impairment

Not studied in patients with hepatic impairment.

Renal Impairment

Clearance of golodirsen was found to be reduced in non-DMD adults with CKD; renal function was assessed using eGFR. (See Special Populations under Pharmacokinetics.) Because of the effect of reduced skeletal muscle mass on creatinine measurements in DMD patients, eGFR values and definitions for various CKD stages cannot be generalized from these non-DMD adults to pediatric patients with DMD.

Closely monitor patients with known renal impairment during treatment with golodirsen.

Common Adverse Effects

Headache, pyrexia, fall, abdominal pain, nasopharyngitis, cough, vomiting, nausea.

Drug Interactions

In vitro data indicate low potential for drug interactions.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Not metabolized by hepatic microsomal enzymes.

Does not inhibit CYP isoenyzmes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5 in vitro.

Does not induce CYP2B6 or 3A4. Weak inducer of CYP1A2.

Drugs Affecting or Affected by Membrane Transporters

Not a substrate or potent inhibitor of organic anion transporter (OAT) 1 or 3, organic cation transporter (OCT) 2, organic anion transporting protein (OATP) 1B1 or 1B3, multidrug and toxin extrusion (MATE) transporter 1 or 2K, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), or multidrug resistance protein (MRP) 2.

Golodirsen Pharmacokinetics

Absorption

Bioavailability

Following IV administration, peak plasma concentrations observed at the end of infusion at approximately 1 hour.

Exposure increases in a dose-proportional manner; minimal accumulation with weekly dosing.

Special Populations

Effects of renal impairment on pharmacokinetics of golodirsen following single IV dose of 30 mg/kg evaluated in non-DMD adults with CKD; cannot be generalized to pediatric patients with DMD. (See Renal Impairment under Cautions.)

Adults with stage 2 CKD (eGFR of 60 to <90 mL/minute per 1.73 m²): AUC increased approximately 1.2-fold with no change in peak plasma concentration.

Adults with stage 3 CKD (eGFR of 30 to <60 mL/minute per 1.73 m²): AUC and peak plasma concentration increased approximately 1.9- and 1.2-fold, respectively.

Distribution

Extent

Not known whether distributed into human milk.

Plasma Protein Binding

33–39%; independent of concentration.

Elimination

Metabolism

Not metabolized by hepatic microsomal enzymes.

Elimination Route

Principally excreted in urine unchanged.

Half-life

3.4 hours.

Stability

Storage

Parenteral

Injection concentrate

Unopened vials: 2–8°C; do not freeze. Protect from light; store in original carton until use.

Diluted solution: May store at 2–8°C for ≤ 24 hours; do not freeze.

Compatibility

Parenteral

Solution Compatibility

Compatible
Sodium chloride 0.9%

Actions

Antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass.
In patients with DMD, frameshift mutations in the dystrophin gene disrupt the translational reading frame, resulting in the production of a nonfunctional dystrophin protein; approximately 63% of these mutations occur between exons 45 and 55.
Golodirsen selectively binds to and promotes exclusion of exon 53 in dystrophin pre-mRNA, restoring the mRNA reading frame and producing an internally truncated, yet partially functional, form of dystrophin similar to that produced in Becker muscular dystrophy (a less severe type of muscular dystrophy).

Advice to Patients

Risk of hypersensitivity. Importance of advising patients (or their caregivers) to seek immediate medical care if they experience signs or symptoms of hypersensitivity reactions (e.g., rash, pyrexia, pruritus, urticaria, dermatitis, skin exfoliation).
Risk of renal toxicity; advise patients of the importance of monitoring for renal toxicity during therapy.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses (e.g., renal disease).
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.