The US Food and Drug Administration has issued its strongest safety alert for the gene therapy Elevidys, adding a Boxed Warning and sharply restricting who can receive the treatment after fatal cases of acute liver failure in non-ambulatory children with Duchenne muscular dystrophy (DMD).

 

The agency approved sweeping new labeling that limits Elevidys to ambulatory patients aged four and older with a confirmed DMD gene mutation. The decision eliminates the therapy’s previous indication for non-ambulatory patients — a move triggered by deaths and other severe liver complications reported earlier this year.

 

Elevidys, an AAVrh74-based gene therapy, came under scrutiny in June when the FDA disclosed two fatal cases in non-ambulatory boys who developed dangerously high liver enzyme levels and required hospitalization within two months of infusion. A third patient survived but experienced a cascade of complications, including mesenteric vein thrombosis, bowel ischemia, necrosis, and portal hypertension. The manufacturer subsequently halted distribution for non-ambulatory patients.

 

Following a full safety review, the FDA’s updated labeling includes: Boxed Warning detailing risks of severe liver injury and fatal acute liver failure; Removal of the indication for non-ambulatory patients; New Limitations of Use section; and Broad updates across safety, dosing, adverse reaction, clinical study, and counseling sections;

 

The revised guidance urges weekly liver tests for at least three months, and recommends patients stay near an equipped medical facility for two months after treatment. The FDA warns caregivers to seek immediate medical attention for jaundice, missed steroid doses, vomiting, or changes in mental status.

 

Because corticosteroids used with Elevidys can suppress immune function, the agency cautions that patients may face heightened infection risks — including potentially fatal complications. Weekly cardiac injury monitoring is also recommended for one month after infusion.

 

Elevidys is now contraindicated in patients with deletions involving DMD exons 8 or 9 and not recommended for those with preexisting liver impairment, recent vaccinations, or recent or active infections.

 

To further track safety concerns, the FDA is requiring the manufacturer to launch a postmarketing observational study of roughly 200 DMD patients, with at least 12 months of follow-up and ongoing liver assessments.

 

The FDA is urging doctors and families to report liver injuries or other adverse events through the agency’s MedWatch reporting system.