FDA updates Elevidys labeling with boxed warning and revised indication following reports of fatal liver injury

The FDA has approved revised labeling for delandistrogene moxeparvovec-rokl (Elevidys), including the addition of a Boxed Warning and a narrower indication for use in Duchenne muscular dystrophy (DMD). These actions follow reports of fatal acute liver failure in non-ambulatory pediatric patients treated with the gene therapy.

Elevidys is an AAVrh74 adeno-associated virus vector–based gene therapy approved for use in certain individuals with DMD. In June 2025, the agency issued a CBER Safety Communication after two non-ambulatory pediatric males with DMD experienced “fatal acute liver failure” following treatment. According to the FDA, “the manufacturer voluntarily paused distribution of Elevidys for use in non-ambulatory patients” after these reports.

What prompted the labeling changes?

The agency reported that in both fatal cases, patients developed significantly elevated liver enzymes and required hospitalization within two months after infusion. An additional non-fatal case of acute liver injury included complications such as “mesenteric vein thrombosis, bowel ischemia and necrosis, and portal hypertension.”

Following evaluation of available safety data, the FDA approved substantial revisions to the product labeling. These include:

• Addition of a Boxed Warning describing the risk of serious liver injury and acute liver failure, including fatal outcomes
• Limiting the indication to ambulatory patients with DMD who are 4 years of age or older with a confirmed DMD gene mutation
• Removal of the indication for non-ambulatory patients
• Addition of a Limitations of Use statement
• Updates across multiple safety, dosing, and clinical sections of the label
• Inclusion of a new Medication Guide for patients and caregivers

Which patients remain eligible for treatment?

The revised indication restricts use to ambulatory individuals aged 4 years or older with a confirmed mutation in the DMD gene. Elevidys is now contraindicated in patients with deletions involving DMD exons 8 and/or 9.

The FDA also added limitations recommending against use in patients with preexisting liver impairment or recent vaccination, or in those with recent or active infections.

What monitoring is recommended?

The updated labeling outlines several monitoring requirements intended to identify and manage potential treatment-related complications:

• Liver function monitoring: Weekly testing is advised for at least 3 months after infusion. Patients should stay near an appropriate medical facility for at least 2 months after treatment.
• Symptoms requiring urgent medical attention: Patients should contact a clinician immediately if they experience “yellowing of the skin or eyes,” missed or vomited corticosteroid doses, or “a change in mental status.”
• Infection risk: The labeling notes that corticosteroid therapy may suppress immune function, heightening susceptibility to infection and possible serious complications, including death.
• Cardiac monitoring: Weekly testing of troponin-I for 1 month following treatment is recommended.

What postmarketing data will be required?

To further assess the risk of serious liver injury, the FDA is requiring a postmarketing observational study. The manufacturer must enroll approximately 200 patients with DMD and follow them for at least 12 months after receiving Elevidys, including periodic liver function assessments.

How should adverse events be reported?

The agency encourages clinicians and patients to report adverse events, including cases of liver injury, to the FDA MedWatch program online or by phone at 1-800-FDA-1088.

The FDA stated that the updated labeling and warnings are intended to support safer clinical decision-making for patients with DMD who may be candidates for this gene therapy.

Reference

FDA. FDA Approves New Safety Warning and Revised Indication that Limits Use for Elevidys Following Reports of Fatal Liver Injury. FDA. November 14, 2025. Accessed November 14, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-new-safety-warning-and-revised-indication-limits-use-elevidys-following-reports-fatal?utm_medium=email&utm_source=govdelivery