FDA rejects second drug Sarepta for the treatment of Duchenne muscular dystrophy



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Sarepta Therapeutics had a surprising setback on Monday when the Food and Drug Administration rejected its application to market a second drug for the treatment of children with Duchenne muscular dystrophy, a hereditary disease resulting in muscle wasting.

In a statement, Sarepta said the FDA had refused approval for its drug, called Vyondys 53, because of the risk of intravenous infusion port infections and kidney toxicity seen in animal experiments.

Sarepta shares fell 13% to $ 105 after trading hours. The stock ended the normal trading session down 4%.

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The FDA has not issued its own statement explaining its negative decision, but the rejection of Vyondys 53 is a rare case where the agency was repressed against a company that was seeking to quickly obtain the approval of the company. A drug against a rare disease based on an early biomarker – and before substantial evidence. the benefit of the patient was obtained.

Rapid authorizations for rare disease drugs have exploded and become almost routine in recent years as the FDA has established comprehensive rules to accelerate drug development for unmet medical needs. The decision to reject Vyondys 53 could therefore represent a new and more restrictive regulatory policy for the FDA, which could affect all companies developing drugs for rare diseases.

But it could also concern only Sarepta, which has for many years maintained conflicting relations with the agency.

"We are very surprised to have received the full response letter this afternoon," Sarepta CEO Doug Ingram said in a statement. "During its review, the agency did not raise any issues suggesting the non-amenability of golodirsen, including the problems underlying the complete response letter." Golodirsen is the scientific name of Vyondys 53.

The company has provided the FDA with data showing that Vyondys 53, given as a weekly infusion, resulted in a slight increase in a major muscle protein called dystrophin, which is usually lacking in children with Duchenne.

No data showing Vyondys 53 capable of improving muscular function in patients with Duchenne or slowing the progression of the disease has been collected or submitted. Sarepta was initially betting on a quick FDA approval, before having to confirm the benefits of treatment in a subsequent clinical trial.

Sarepta used this same strategy in 2016 to obtain accelerated approval of its first Duchenne-based drug, called Exondys 51. This decision was controversial. External FDA advisers – and even some of its own employees – have concluded that there is not enough evidence to prove Exondys 51 in the treatment of Duchenne.

FDA officials, led by Dr. Janet Woodcock, ignored the negative recommendations and still approved the drug, in part because of intense pressure from the families of children with Duchenne.

With the approval of 2016, Sarepta was able to turn Exondys 51 into a product generating annual sales of between $ 300 million and $ 400 million. However, the company has lagged behind the years required to complete the clinical trials required by the FDA to confirm the actual benefit of the drug, as STAT reported last week.

Sarepta's delinquency on Exondys 51 may have irritated the FDA enough to play a role in the agency's decision to overturn Vyondys 53 on Monday.

Sarepta has announced plans to meet with the FDA to resolve the issues that led the FDA to reject the drug. A confirmatory study of Vyondys 53 is currently underway, but data on improvements in muscle function are not expected for three to four years.

Vyondys 53 is designed to treat patients whose Duchenne is caused by an error in the DNA sequence called exon 53. About 8% of the 5,000 Duchenne patients in the United States carry the exon error 53. Exondys 51 is used to treat the 13% of patients with a disease caused by an error in the DNA sequence called exon 51.

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