In August the FDA was skeptical about Sarepta Therapeutics Inc.’s injectable Vyondys 53 (golodirsen), but that’s changed as the company just received accelerated approval for the Duchenne muscular dystrophy (DMD) follow-on therapy, the first treatment specifically for this subtype.

The nod to treat DMD patients with a confirmed dystrophin gene mutation that is amenable to exon 53 skipping will affect about 8% of DMD patients, a group not reached by Sarepta’s first commercial product, Exondys 51 (eteplirsen). Duchenne is a rare, fatal X-linked degenerative neuromuscular disorder, affecting one in every 3,500 to 5,000 males born worldwide. It is caused by genetic changes blocking functional dystrophin, a protein vital for strengthening and protecting muscle fibers.

In August, the FDA sent Sarepta a complete response letter, declining accelerated approval and citing two concerns: infection risk related to I.V. infusion ports and renal toxicity noted in golodirsen preclinical models and observed following administration of other antisense oligonucleotides.

The agency said it based the approval on Sarepta’s data showing the surrogate endpoint of an increase in dystrophin production in the skeletal muscle observed in some patients treated with the drug. That data showed an increase in dystrophin production that is reasonably likely to predict clinical benefit in patients, according to the FDA.

H.C. Wainwright analysts were startled by the sudden approval: “If the NDA package was not approvable four months ago, it cannot suddenly become approvable without significant new data, and potential reflects some contrived decision-making within the agency, in our view.”

SVB Leerink analysts were also taken aback by the about face: “While the news came as a surprise to us, it did confirm our theory that Vyondys 53’s complete response letter was merely a bump in the road towards approval with the FDA leaving [Sarepta] to twist in the wind for a short while before ultimately approving the drug.”

As part of the accelerated approval process, the FDA is requiring Sarepta to conduct a clinical trial to confirm Vyondys 53's clinical benefit. The ongoing study is designed to assess whether Vyondys 53 improves motor function of DMD patients with a confirmed mutation of the dystrophin gene amenable to exon 53 skipping. If the trial fails to verify clinical benefit, the FDA said it may initiate proceedings to withdraw approval of the drug.

While making its decision, the agency said it took potential risks of using the drug into account, the disease’s lack of available therapies, as well as its life-threatening, debilitating nature.

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