Sarepta Therapeutics
Contested approvals, patient deaths and a standoff with the FDA
Sarepta Therapeutics develops treatments for Duchenne muscular dystrophy (DMD), a fatal muscle-wasting disease that mainly affects boys. It is also one of the most divisive companies in US biotech. Its first drug, Exondys 51, was approved in 2016 after an internal FDA dispute; its gene therapy Elevidys was approved in 2023 over staff objections, failed its confirmatory trial's primary endpoint, and in 2025 was linked to patient deaths and a public standoff with regulators.
Questions
Why is Sarepta so controversial?
Twice, senior FDA officials overruled their own review teams to approve Sarepta drugs on surrogate biomarkers without confirmed functional benefit — then in 2025 patient deaths from acute liver failure led to a public standoff over whether to halt shipments.
Sarepta sits at the centre of a long-running argument about how much evidence regulators should demand before approving drugs for devastating rare diseases. Twice, senior FDA officials have overruled the agency's own reviewers to approve Sarepta products on the basis of a biomarker (dystrophin or micro-dystrophin production) rather than demonstrated improvement in how patients function. Patient families and advocacy groups have strongly supported these approvals, arguing that boys with DMD cannot wait.
Q2What happened with the approval of Exondys 51 in 2016?
An FDA advisory panel voted 7-6 against the drug, the review team recommended rejection, and the drug increased dystrophin to only about 0.28% of normal — yet the head of FDA's drug centre overruled both, and two reviewers resigned.
Exondys 51 (eteplirsen) was approved in September 2016 under accelerated approval based on a study of just 12 boys. An FDA advisory panel had voted 7-6 against it and the review team recommended rejection. The drug increased dystrophin only to about 0.28% of normal levels on average, while reviewers believed more than 10% might be needed for clinical impact.
Q3Did Sarepta complete the confirmatory trial for Exondys 51?
Not on the original timeline — the FDA set a November 2020 completion deadline that the company did not meet, illustrating a broader pattern in which accelerated approvals for desperate patient populations are politically difficult to withdraw.
Not on the original timeline. When the FDA granted accelerated approval, it required Sarepta to run a randomised controlled trial to verify that the drug actually slows disease progression. According to a review in the Annals of Internal Medicine, the FDA initially set a November 2020 deadline for completing that trial, which the company did not meet.
Q4How was the Elevidys gene therapy approved?
An advisory committee voted only 8-6 in favour, FDA clinical and statistics teams found the data inadequate, and the biologics centre head again overruled staff — then expanded the label in 2024 even after the confirmatory trial failed its primary endpoint.
Elevidys, a one-time gene therapy priced at $3.2 million, received accelerated approval in June 2023 for ambulatory boys aged 4 and 5. An advisory committee voted only narrowly in favour, 8-6. The FDA's clinical, pharmacology and statistics review teams had found the data not adequate to meet the threshold for approval, and it was Peter Marks, head of the FDA's biologics centre, who decided against their recommendation.
Q5What safety problems emerged with Elevidys in 2025?
Three patients died from acute liver failure following treatment with Elevidys or a related Sarepta gene therapy using the same AAV vector, prompting the FDA to revoke the platform's technology designation and request a halt to all shipments.
Beginning in March 2025, patients died after treatment. CGTLive's timeline records a first death from acute liver failure in a non-ambulatory patient on March 18, 2025 and a second on June 15, after which dosing of non-ambulatory patients was suspended. A third death, in a 51-year-old man given a related Sarepta gene therapy (SRP-9004) for limb-girdle muscular dystrophy using the same AAVrh74 vector, also involved liver failure.
Q6What was the standoff between Sarepta and the FDA?
On July 18, 2025, the FDA informally asked Sarepta to pause all Elevidys shipments — Sarepta initially refused, then reversed days later, while also confirming a third death it had reported to the FDA two weeks earlier but not disclosed publicly.
On July 18, 2025, the FDA informally asked Sarepta to pause all Elevidys shipments. Sarepta initially said it would not comply, before reversing its position several days later. As BioPharma Dive reported, this was a highly unusual public confrontation between a company and its regulator. Compounding it, Sarepta had reported the third death to the FDA on July 3 but did not disclose it publicly, confirming it only hurriedly later; analysts questioned why it had not been mentioned on a conference call held days earlier.
Q7Is Elevidys still available?
Yes — but only for ambulatory patients aged 4 and older. Non-ambulatory patients were removed from the label in November 2025 following the deaths, and the European Medicines Agency has refused EU authorisation.
Yes, but in a narrower form. On July 28, 2025, the FDA recommended Sarepta resume shipments for ambulatory patients, after concluding that the death of an 8-year-old boy in Brazil was unrelated to the product. On November 14, 2025, a label update added a boxed warning for acute serious liver injury and acute liver failure and removed eligibility for non-ambulatory patients.
Q8What are the main criticisms of Sarepta's approach?
Four points: approvals resting on surrogate biomarkers the FDA's own scientists doubted; prices of $300,000/year and $3.2 million/dose for unconfirmed benefit; slow or negative confirmatory trials; and safety disclosures in 2025 that fell short of expected transparency.
Critics make four points. First, that its key approvals rested on surrogate biomarkers the FDA's own scientists doubted, and on the personal judgement of senior officials overriding review teams. Second, that its prices, around $300,000 a year for Exondys 51 and $3.2 million per dose for Elevidys, are extraordinarily high for unconfirmed benefit; ICER's chief medical officer argued in JAMA that such approvals cast doubt on the accelerated approval pathway. Third, that confirmatory trials have been slow or negative without leading to withdrawal.
Q9How much do Sarepta's drugs cost?
Exondys 51 costs around $300,000 per year and Elevidys $3.2 million per dose, making Sarepta's products among the most expensive in medicine — in a disease with a small patient population and, as yet, unconfirmed functional benefit.
Sarepta's products are among the most expensive in medicine. Exondys 51, given by weekly infusion, was priced at around $300,000 a year per patient at launch. Elevidys, the one-time gene therapy, carries a wholesale acquisition cost of $3.2 million. A review in the Annals of Internal Medicine noted that Sarepta's exon-skipping drugs have been controversial partly because of high US prices combined with questionable evidence and delayed confirmatory testing.
Q10What did Elevidys's confirmatory trial show?
The phase 3 EMBARK trial failed its primary endpoint: treated boys improved by 2.6 points on the motor scale versus 1.9 on placebo — a difference that was not statistically significant — yet the FDA expanded the label in 2024 anyway.
The phase 3 EMBARK trial was designed to confirm that Elevidys improves function, as required for its accelerated approval. It enrolled 125 ambulatory boys aged 4 to 7 and measured change in the North Star Ambulatory Assessment motor score at 52 weeks. Treated boys improved by 2.6 points versus 1.9 on placebo, a difference that was not statistically significant, so the trial failed its primary endpoint.
Q11What should I watch for next with Sarepta?
Whether longer-term data support Elevidys's benefit in ambulatory patients, whether the boxed-warning regime prevents further liver deaths, and whether the FDA under current leadership applies tougher standards to accelerated approvals in DMD.
Key issues include whether longer-term data support Elevidys's benefit in ambulatory patients, whether the boxed-warning regime prevents further liver-related deaths, and whether the FDA under current leadership applies tougher standards to accelerated approvals in DMD. The broader DMD field is also under scrutiny: in August 2026 an FDA advisory committee voted 9-3 against another company's DMD cell therapy, suggesting the agency's advisers are taking a more sceptical line.