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FDA ditches Sarepta’s antisense oligonucleotide treatment for DMD

Sarepta Therapeutics has announced that the FDA has rejected its New Drug Application for golodirsen, developed for treating Duchenne muscular dystrophy (DMD). The company’s stock dropped as much as 13% in after-hours trading following the news.

Golodirsen, the follow-up to Exondys 51 (Sarepta’s first approved treatment for DMD), is an antisense oligonucleotide used to skip the exon 53 in order to restore the reading frame of the dystrophin protein, encoded by the DMD gene.

DMD, one of the most common inherited genetic diseases, is a fatal genetic neuromuscular disorder affecting an estimated one in approximately every 3,500 – 5,000 males born worldwide.

FDA laid out the reasons for the rejection in a complete response letter to Sarepta. In February this year, the company had submitted a New Drug Application seeking accelerated approval of golodirsen injection. The FDA has now denied the drug for two reasons: the risk of infection linked to the port of infusion of the drug where the devices are placed to give doctors access to the vein and the risk of kidney toxicity as observed in animal studies.

The reasons have taken Sarepta by surprise as the company claims that the kidney toxicity was seen in animal models that got doses that were 10 times higher than the dose used in clinical studies. Kidney toxicity was not seen in the study on which golodirsen’s application was based. Sarepta will “immediately request a meeting with the FDA” to clarify and figure out its next steps.

Back in 2016, Sarepta managed to receive the FDA approval for Exondys 51, its first’s antisense oligonucleotide treatment for DMD, through much controversy.
Sarepta’s New Drug Application seeking the accelerated approval for golodirsen was based on a study testing it in 25 boys with DMD amenable to exon 53 skipping. The study showed that the drug boosted the amount of dystrophin. If golodirsen works as predicted, it can be used to treat approximately 8% of the mutations known to cause DMD. In another ongoing study, the ESSENCE trial, the company is studying golodirsen alongside another DMD drug, casimersen.

Doug Ingram, Sarepta CEO commented: “Over the entire course of its review, the agency did not raise any issues suggesting the non-approvability of golodirsen, including the issues that formed the basis of the Complete Response Letter. We will work with the Division to address the issues raised in the letter and, to the fullest extent possible, find an expeditious pathway forward for the approval of golodirsen. We know that the patient community is waiting.”

Source: FDA surprises Sarepta by spurning its 2nd Duchenne drug; News

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