VYONDYS 53
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VYONDYS 53 (VYONDYS 53).
VYONDYS 53 is a morpholino antisense oligonucleotide that binds to exon 53 of dystrophin pre-mRNA, leading to skipping of exon 53 during mRNA processing and restoration of the dystrophin mRNA reading frame. This results in production of a truncated but functional dystrophin protein in patients with Duchenne muscular dystrophy (DMD) who have confirmed mutations amenable to exon 53 skipping.
| Metabolism | VYONDYS 53 is not metabolized by cytochrome P450 enzymes; it is predominantly eliminated by renal excretion as unchanged drug. |
| Excretion | Renal: >90% as unchanged drug and metabolites; fecal and biliary: minimal (<5%) |
| Half-life | Terminal elimination half-life: 28-32 days in plasma; supports weekly dosing regimen |
| Protein binding | >90% bound to plasma proteins, primarily albumin |
| Volume of Distribution | 0.25-0.35 L/kg, indicating distribution primarily in extracellular fluid and vascular space |
| Bioavailability | IV: 100% (only route of administration) |
| Onset of Action | IV: Clinical benefit (dystrophin production) observed after 24-48 weeks of continuous treatment |
| Duration of Action | IV: Sustained dystrophin expression for weeks after discontinuation; clinical effect maintained with weekly dosing |
30 mg/kg intravenously once weekly.
| Dosage form | SOLUTION |
| Renal impairment | No specific dose adjustment recommended; renal impairment not studied. |
| Liver impairment | No specific dose adjustment recommended; hepatic impairment not studied. |
| Pediatric use | 30 mg/kg intravenously once weekly for patients aged 4 years and older. |
| Geriatric use | No specific adjustment; clinical studies did not include sufficient numbers of patients aged 65 and over. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VYONDYS 53 (VYONDYS 53).
| Breastfeeding | No data on excretion in human milk; M/P ratio unknown. Consider developmental benefits of breastfeeding vs maternal need for drug. |
| Teratogenic Risk | No human data available; animal studies show no evidence of fetal harm. However, risk cannot be ruled out. Avoid use in pregnancy unless benefit outweighs unknown risks. |
| Fetal Monitoring | Monitor maternal liver function tests and renal function. No fetal monitoring specific to VYONDYS 53. |
■ FDA Black Box Warning
None.
| Serious Effects |
None.
| Precautions | ["Hypersensitivity reactions including angioedema, rash, and urticaria","Renal toxicity observed in animal studies; monitor renal function before and during treatment"] |
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| Fertility Effects | No human fertility studies; animal studies show no adverse effects on male or female fertility. |