FDA surprises Sarepta by spurning its 2nd Duchenne drug

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Like Exondys 51, Sarepta Therapeutics' golodirsen is designed to treat a group of Duchenne muscular dystrophy patients with a certain type of mutation. (kai kalhh)

Three years ago, Sarepta Therapeutics pushed its first drug through a controversial approval, but its second drug is facing a different fate. 

The FDA rejected the New Drug Application for golodirsen, the follow-up to Exondys 51, Sarepta’s first treatment for Duchenne muscular dystrophy (DMD), the company said in a statement Monday evening. The company’s stock dipped as much as 20% on the news in after-hours trading. 

The agency laid out the reasons for the snub in a Complete Response Letter, Sarepta said. It nixed the drug for two reasons: the risk of infection linked to intravenous infusion ports—devices placed just under the skin to give doctors access to a vein—and kidney toxicity seen in animal studies. 

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But, Sarepta said, kidney toxicity was seen in animals that got doses that were 10 times higher than those used in human studies. Kidney toxicity was not seen in the study on which golodirsen’s application was based, the company said. Sarepta will “immediately request a meeting with the FDA” to figure out its next steps. 

“We are very surprised to have received the Complete Response Letter this afternoon,” Sarepta CEO Doug Ingram said in the statement. “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.” 

RELATED: Sarepta dips on controversial Duchenne hospitalization report 

Like Exondys 51, golodirsen, which Sarepta hopes to sell under the name Vyondys 53, is designed to treat a group of Duchenne patients with a certain type of mutation. Exondys 51 works for about 13% of DMD patients—those whose disease is amenable to exon 51 skipping. If approved, golodirsen would offer treatment to patients with a mutation in exon 53—about 8% of the DMD population. 

That’s not all the two drugs have in common. Sarepta used the same playbook for golodirsen as it did for Exondys 51. 

In 2016, Sarepta scored a speedy approval for Exondys 51 on the strength of a surrogate biomarker endpoint. The company did not present any trial data showing a clinical benefit to patients, so it promised to carry out a trial later on to prove it could improve muscle function in patients. Three years later, the FDA is still waiting for those data. 

“We believe Duchenne patients are benefiting from Exondys 51 and we are conducting the confirmatory clinical trial as fast as possible,” Ingram told Stat News earlier this month. 

RELATED: Sarepta slips on U.K. golodirsen study halt but expects to get back on track

Sarepta had been seeking an accelerated approval for golodirsen 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, the protein missing in children with DMD. However, data that would show improvements in muscle function won’t read out for a few years. 

The company is studying golodirsen alongside another Duchenne drug, casimersen, in a separate study that could serve as a confirmatory study after approval.

Sarepta was down more than 13% after-hours Monday night on the news.

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