The FDA has approved the addition of a Boxed Warning and other labeling changes for the Duchenne muscular dystrophy (DMD) gene therapy delandistrogene moxeparvovec-rokl (Elevidys, Sarepta) after recent reports of posttreatment fatal liver injuries. 

The approved labeling changes, which were submitted by the manufacturer, will include a new statement in the indication section that the treatment should be used only in patients with DMD who are 4 years of age or older and who are ambulatory. The new label removes the indication for nonambulatory patients. 

A Boxed Warning, which is considered to be the FDA’s strictest type of warning, is being included because of reports of fatal acute liver failure in two nonambulatory pediatric males with the disorder, the agency reported this week in a statement. 

Within 2 months of infusion with the drug, both patients had developed elevated liver enzymes that required hospitalization. There was also a report of a serious, though nonfatal, case of acute liver injury. Complications in that case included bowel ischemia and necrosis, mesenteric vein thrombosis, and portal hypertension. 

“After a comprehensive evaluation of the available safety data, FDA has now approved substantial labeling revisions for Elevidys,” the US Department of Health and Human Services (HHS) said in the release.

New Safety, Monitoring Recommendations

DMD is a rare, severe genetic disorder that causes progressive muscle weakness and most commonly affects boys. 

Elevidys, a single-dose adeno-associated virus-based gene transfer infusion therapy, was first approved for certain patients with DMD in 2023. However, the FDA issued a CBER Safety Communication about the drug this past June after receiving the two reports of posttreatment fatal liver failure. 

In addition to a Boxed Warning detailing risk for acute liver failure and both serious and fatal liver injury, and the indication stating that the treatment is for ambulatory patients only, other labeling revisions will include the addition of a new medication guide and limitations-of-use statement, as well as updates to the warning and precautions, dosage, adverse reactions, and patient counseling information sections. 

New labeling also includes safety and monitoring recommendations such as weekly liver function tests for at least 3 months post-treatment, weekly cardiac injury testing for 1 month post-treatment, and specific instances where patients should immediately contact a healthcare provider, such as if they experience yellowing of the skin or eyes. 

In addition, the FDA will require Sarepta to conduct a postmarketing observational study to "further assess the risk of serious liver injury,” the HHS said. 

The study will include 200 patients with DMD, with follow-up of at least 12 months post-treatment that will include liver function assessments, the agency reported.