The Food and Drug Administration (FDA) has granted accelerated approval to Vyondys 53 (golodirsen; Sarepta Therapeutics) injection for the treatment of Duchenne muscular dystrophy (DMD) with confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping.
Golodirsen is an antisense oligonucleotide of the phosphorodiamidate morpholino oligomer (PMO) subclass. It 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.
The accelerated approval of Vyondys 53 was based on the surrogate end point from the phase 1/2 4053-101 trial that demonstrated an increase in dystrophin production from 0.10% of normal at baseline to 1.02% of normal after 48 weeks of treatment. The FDA concluded that the increase in dystrophin production is “reasonably likely to predict clinical benefit in patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 53 skipping.” As part of the accelerated approval process, the Company is conducting an ongoing study (ESSENCE) to confirm the clinical benefit of Vyondys 53 to improve motor function in DMD patients.
With regard to safety, the most common adverse reactions were headache, pyrexia, cough, vomiting, abdominal pain, nasopharyngitis and nausea. Additionally, renal function should be monitored in patients receiving Vyondys 53; while not reported in clinical trials, renal toxicity with golodirsen has been observed in animal studies.
“With today’s accelerated approval, patients with [DMD], a rare and devastating disease, who have a confirmed mutation of the dystrophin gene amenable to exon 53 skipping will now have available the first treatment targeted specifically for this disease subtype,” said Billy Dunn, MD, acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “Use of the accelerated approval pathway will make Vyondys 53 available to patients based on initial data and we look forward to learning more about the drug’s clinical benefit from the ongoing confirmatory clinical trial.”
The product will be supplied in 100mg/2mL single-dose vials. In a press release, Sarepta announced that commercial distribution of Vyondys 53 in the US will commence immediately.
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