Overview
11 DESCRIPTION VYONDYS 53 (golodirsen) injection is a sterile, aqueous, preservative-free, concentrated solution for dilution prior to intravenous administration. VYONDYS 53 is a clear to slightly opalescent, colorless liquid, and may contain trace amounts of small, white to off-white amorphous particles. VYONDYS 53 is supplied in single-dose vials containing 100 mg golodirsen (50 mg/mL).
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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 )]. 12.2 Pharmacodynamics After treatment with VYONDYS 53, all patients evaluated (n=25) in Study 1 Part 2 [see Clinical Studies ( 14 )] had an increase in skipping of exon 53 demonstrated by reverse transcription polymerase chain reaction (RT-PCR), compared to baseline.
Indications
- 1 INDICATIONS AND USAGE 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 )] . Continued approval for this indication may be contingent upon verification of a clinical benefit in confirmatory trials.
Common Doses
- Refer to label
Dosage
2 DOSAGE AND ADMINISTRATION 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.
Contraindications
- 4 CONTRAINDICATIONS 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 )] . VYONDYS 53 is contraindicated in patients with serious hypersensitivity to golodirsen or to any of the inactive ingredients in VYONDYS 53. ( 4 , 5.1 )
Side Effects
- 6 ADVERSE REACTIONS 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.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.