About VYONDYS 53

WHAT IS VYONDYS 53 (golodirsen)?

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. Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.

A genetic test is required to confirm that a patient's mutation of the DMD gene is amenable to exon 53 skipping. For more information about genetic testing resources for patients, visit Parent Project Muscular Dystrophy’s (PPMD) Decode Duchenne website.

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Clinical Trial results

VYONDYS 53 modified gene expression in all patients evaluated, as measured by RT-PCR.^1,3

*MoA confirmed by RT-PCR. Skipping occurred at the correct location as confirmed by immunofluorescence staining.
RT-PCR = reverse transcription polymerase chain reaction.
MoA = mechanism of action.
mRNA = messenger ribonucleic acid.

EXON SKIPPING OCCURRED IN ALL 25 EVALUATED STUDY PARTICIPANTS.¹

A change from baseline in mean percent exon 53 skipping of 16.4% ± 10.6% at Part 2, Week 48 was observed (n=25).²

VYONDYS 53 increased dystrophin production over baseline.¹

y-axis represents 5% on a scale of 100%

• Efficacy was assessed based on change from baseline in the dystrophin protein level (measured as % of the dystrophin level in healthy subjects, i.e., % of normal) at Week 48 of Part 2.


• Mean dystrophin levels increased from 0.10% (SD 0.07) of normal at baseline to 1.02% (SD 1.03) of normal by Week 48 of Study 1 Part 2, with a mean change in dystrophin of 0.92% (SD 1.01) of normal levels (p<0.001); the median change from baseline was 0.88%.


• This increase in dystrophin protein expression positively correlated with the level of exon skipping.


• Dystrophin levels assessed by western blot can be meaningfully influenced by differences in sample processing, analytical technique, reference materials, and quantitation methodologies. Therefore, comparing dystrophin results from different assay protocols will require a standardized reference material and additional bridging studies.


• Patients treated with VYONDYS 53 showed an average dystrophin increase of 15.96 fold.^2,4

Dystrophin expression over baseline in patients treated with VYONDYS 53.¹

SAFETY PROFILE IN PATIENTS WHO RECEIVED VYONDYS 53¹

• Hypersensitivity reactions, including 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 or interrupting the VYONDYS 53 therapy.


• Kidney toxicity was observed in animals who received golodirsen. Although kidney toxicity was not observed in the clinical studies with VYONDYS 53, the clinical experience with VYONDYS 53 is limited, and kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides.


• Kidney function should be monitored in patients taking VYONDYS 53. Because of the effect of reduced skeletal muscle mass on creatinine measurements, creatinine may not be a reliable measure of kidney function in DMD patients. Serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio should be measured before starting VYONDYS 53. Consider also measuring glomerular filtration rate using an exogenous filtration marker before starting VYONDYS 53. During treatment, monitor urine dipstick every month, and serum cystatin C and urine protein-to-creatinine ratio every three months.
  
  Only urine expected to be free of excreted VYONDYS 53 should be used for monitoring of urine protein. Urine obtained on the day of VYONDYS 53 infusion prior to the infusion, or urine obtained at least 48 hours after the most recent infusion, may be used. Alternatively, use a laboratory test that does not use the reagent pyrogallol red, as this reagent has the potential to cross react with any VYONDYS 53 that is excreted in the urine and thus lead to a false positive result for urine protein.
  
  If a persistent increase in serum cystatin C or proteinuria is detected, refer to a pediatric nephrologist for further evaluation.

In the VYONDYS 53 clinical development program, 58 patients received at least one IV dose of VYONDYS 53, ranging between 4 mg/kg (0.13 times the recommended dosage) and 30 mg/kg (the recommended dose). All patients were male and had genetically confirmed DMD. 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.

ADVERSE REACTIONS OBSERVED ≥20% OF TREATED PATIENTS AND GREATER THAN PLACEBO WERE (VYONDYS 53, PLACEBO)

• Other adverse reactions that occurred at a frequency greater than 5% of VYONDYS 53-treated patients and at a greater frequency than placebo were: administration site pain, back pain, pain, diarrhea, dizziness, ligament sprain, contusion, influenza, oropharyngeal pain, rhinitis, skin abrasion, ear infection, seasonal allergy, tachycardia, catheter site related reaction, constipation, and fracture.

Please see the full Prescribing Information for VYONDYS 53 (golodirsen).

Dosing and Administration

WHO IS ELIGIBLE FOR VYONDYS 53?

VYONDYS 53 should only be administered to patients who have a confirmed mutation of the DMD gene that is amenable to skipping exon 53.

WHAT ARE THE DOSING RECOMMENDATIONS?

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.

The recommended dosage of VYONDYS 53 is 30 mg/kg administered once weekly as a 35 to 60 minute intravenous (IV) 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.

Application of a topical anesthetic cream to the infusion site prior to administration of VYONDYS 53 may be considered.

If a hypersensitivity reaction occurs, consider slowing the infusion or interrupting the VYONDYS 53 therapy.

Advise patients and/or caregivers that hypersensitivity reactions, including rash, pyrexia, pruritus, urticaria, dermatitis, and skin exfoliation have occurred in patients who were treated with VYONDYS 53. Instruct them to seek immediate medical care should they experience signs and symptoms of hypersensitivity.

Inform patients nephrotoxicity has occurred with drugs similar to VYONDYS 53. Advise patients of the importance of monitoring for kidney toxicity by their healthcare providers during treatment with VYONDYS 53.

VYONDYS 53 injection is supplied in single-dose vials containing 100 mg/2 mL (50 mg/mL) golodirsen. The solution is a clear to slightly opalescent, colorless liquid and may contain trace amounts of small, white to off-white amorphous particles.

Store VYONDYS 53 at 2°C to 8°C (36°F to 46°F). Do not freeze. Store VYONDYS 53 in the original carton until ready for use to protect from light.

Download Dosing and Administration Guide