Three deaths attributed to acute liver failure appear to have occurred following regular treatment or investigational therapy.
In an about-face capping a tumultuous week that included
For Sarepta, it is a stunning and humbling reversal after the company defied FDA on Friday, July 18, by refusing to voluntarily suspend shipments of Elevidys at the agency’s request following three deaths, apparently due to acute liver failure, which FDA traced back to delandistrogene moxeparvovec treatments or investigational gene therapy using the same serotype, AAVrh74, found in the drug (3,4).
In light of those developments, FDA at the time of its request also placed Sarepta’s investigational gene therapy clinical trials for limb-girdle muscular dystrophy (LGMD) on hold and revoked the platform technology designation for AAVrh74 (3). According to the Muscular Dystrophy Association, LGMD typically manifests in the proximal muscles, nearest the hips and shoulders; while Duchenne muscular dystrophy primarily affects the same muscle groups, its early childhood onset and overwhelming prevalence in male patients versus female have given it increased focus (5).
“We’ve shown that this FDA takes swift action when patient safety is at risk,” FDA Commissioner
“Protecting patient safety is our highest priority, and FDA will not allow products whose harms are greater than benefits,”
On July 16, as Sarepta said it was engaging with FDA to add acute liver injury and acute liver failure warnings to its delandistrogene moxeparvovec labels, as well as pausing shipments of the drug for non-ambulant patients, the company said it would be immediately laying off approximately 500 employees, equivalent to 36% of its workforce at the time, which Sarepta said would account for $120 million out of a targeted $400 million in annual cost reductions for 2026 (2).
The company announced its intention to refocus its pipeline on a potentially best-in-class small interfering RNA (siRNA) platform while de-emphasizing most of its gene therapies in development for LGMD (2).
“We will continue to drive performance of Elevidys and our three PMOs [phosphorodiamidate morpholino oligomers] in service of the Duchenne community those therapies benefit, and with our financial performance, we will advance our high-value, focused pipeline of programs for rare genetic diseases, primarily relying on the siRNA platform, while ensuring we meet our financial obligations,” Sarepta CEO
On July 21, Ingram called Sarepta’s decision to heed FDA’s request a “painful” one.
“Individuals with Duchenne are losing muscle daily and in need of disease-modifying options,” he said (1). “It is important for the patients we serve that Sarepta maintains a productive and positive working relationship with FDA, and it became obvious that maintaining that productive working relationship required this temporary suspension while we address any questions that FDA may have and complete the Elevidys label supplement process.”
FDA approved Sarepta’s delandistrogene moxeparvovec for ambulatory Duchenne muscular dystrophy patients aged 4 and older, with a confirmed mutation in the DMD gene, in June 2024, with the drug having been granted accelerated approval for non-ambulatory patients one year prior (3). Given the latest safety information, FDA said it was restricting the treatment’s indication to ambulatory patients only.
1. Sarepta Therapeutics.
2. Sarepta Therapeutics.
3. FDA.
4. Sarepta Therapeutics.
5. Laverty, C., ed.
