Four months after rejecting Sarepta’s Duchenne muscular dystrophy drug Vyondys 53, the FDA has turned on a dime and granted it an accelerated approval.
The decision comes out of the blue, given that the US regulator said in August it was concerned about a risk of infections linked to the intravenous infusion port used to administer the therapy as well as kidney toxicity.
Sarepta appealed that decision through the FDA dispute resolution protocol and has won a turnaround, allowing it to move ahead with a launch of the drug “immediately.”
The FDA now says that Vyondys 53 (golodirsen) is “reasonably likely” to have a clinical benefit in DMD and that its decision takes into account “the potential risks associated with the drug, the life-threatening and debilitating nature of the disease and the lack of available therapy”.
Vyondys 53 (golodirsen) is Sarepta’s second approved DMD therapy after Exondys 51 (eteplirsen), the first disease-modifying treatment to be introduced in the US for the inherited muscle-wasting disease three years ago which made around $287m in sales in the first nine months of the year.
Like its predecessor, Vyondys 53 is designed to increase production in the skeletal muscle of dystrophin, a protein that helps keep muscle cells intact and is absent in patients with DMD.
Vyondys uses the same ‘exon skipping’ mechanism, but helps patients with the exon 53 mutation rather than the exon 51 mutation targeted by Exondys 51. These patients represent around 8% of the DMD population, while those with the exon 51 mutation account for around 13%.
“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,” said Billy Dunn, head of the FDA’s Office of Neuroscience.
Sarepta has indicated it will launch Vyondys 53 at a price that is “at parity” with Exondys 51, which costs around $300,000 per year ahead of rebates and discounts. It could face its first competition fairly soon however after rival NS Pharma filed for approval of its exon 53 skipping drug viltolarsen in October.
“In the span of four months, we commenced and completed the formal dispute resolution process culminating in the grant of our appeal, resubmitted our NDA and obtained an approval – a great benefit to DMD patients awaiting treatment,” said the company’s chief executive Doug Ingram.
The company has a third therapy, called casimersen, which it is planning to file shortly with the FDA and targets exon 45 mutations. If that claims approval Sarepta will be able to target around a third of all DMD patients and according to Leerink analysts the franchise could be worth $1.7bn by 2024.
It is also developing gene therapies for DMD in the hope of providing a one-shot therapy to raise dystrophin levels, with phase 1 results reported earlier this year.