Sarepta rises after FDA adds warning label to Elevidys

Shares in Sarepta reversed some of their recent declines after the FDA added a warning label to its Duchenne muscular dystrophy (DMD) gene therapy, ending a protracted period of uncertainty for the company.

There are no major surprises in the change to the warning, which is the addition of a boxed warning that Elevidys (delandistrogene moxeparvovec), and a restriction to its prescribing information to indicate it should only be used in patients who can walk (ambulatory) and aged four and over.

It ties in with the actions already taken by Sarepta and overseas commercial partner Roche to limit the use of Elevidys in this patient group, after cases of acute liver failure – in some cases fatal – in non-ambulatory patients treated with the product.

Non-ambulatory DMD patients tend to be more seriously ill, but so far, the mechanism by which Elevidys causes liver damage in these patients is unclear and under investigation.

One suggestion is that the side effects may be due to an immune response to antigens in the adeno-associated virus (AAV) gene therapy, or the truncated dystrophin protein it expresses in the liver.

The label now calls for a modified pre- and post-infusion oral corticosteroids regimen to minimise the risk of acute liver injury and stricter monitoring requirements in the three months after its one-dose infusion. Patients with preexisting liver impairment, recent vaccinations, or recent/active infections are also excluded from treatment.

The FDA is also requiring Sarepta to conduct an additional post-marketing observational study to further assess the risk of serious liver injury. According to the agency, this study will enrol approximately 200 patients with DMD and focus on evaluating liver function for at least 12 months after administration of Elevidys.

Elevidys generated $820 million for Sarepta last year and $788 million in the first nine months of this year, some tens of millions less than expected due to the usage restrictions, so the end of the uncertainty over the warning label is a relief for Sarepta, even with the restrictions on its use.

"We want to thank the FDA for their thorough and collaborative review," said Louise Rodino-Klapac, Sarepta's head of R&D and technical operations.

"Completion of the safety labelling change for Elevidys will ensure that families and healthcare professionals have clear information, supported by a medication guide, to help understand these updates and guide treatment decisions," she added.

Sarepta said that more than 1,100 people with DMD have been treated to date with the gene therapy, which has been shown in clinical trials to slow declines in motor function and improve patients' physical functioning.

It also said it plans to start a study shortly of a new sirolimus immunosuppressive regimen to see if that can reduce the risk of liver side effects and – potentially at least – make Elevidys an option once again for non-ambulatory DMD patients.

In a statement, patient advocacy group Parent Project Muscular Dystrophy (PPMD) said the update "serves as a reminder that while gene therapy breakthroughs bring promise and hope, serious questions remain about the safety and long-term outcomes of these therapies."

Image by Steve Buissinne from Pixabay