Sarepta reports death of DMD patient given gene therapy Elevidys
Man went into acute liver failure, company working with health authorities
A young man with Duchenne muscular dystrophy (DMD) who received the one-time gene therapy Elevidys (delandistrogene moxeparvovec-rokl) has died due to acute liver failure.
In a statement, the therapy’s developer, Sarepta Therapeutics, said it is continuing to gather and analyze information about this event, which has been reported to relevant health authorities. Elevidys clinical study investigators and prescribing physicians also have been notified, and the company intends to update the therapy’s prescribing information.
“Patient safety and well-being are Sarepta’s top priority,” the company stated.
As detailed in its current prescribing information, acute liver injury is a known possible side effect of Elevidys, and it’s a recognized concern for gene therapies that use adeno-associated virus (AAV) delivery systems. Both animal and human studies show the potential for liver damage with AAV vectors, including elevated liver enzymes and liver failure.
Still, Sarepta noted that acute liver failure leading to death has never been reported with Elevidys, which has been given to more than 800 patients either in clinical trials or as a prescribed therapy.
Duchenne patient had recent viral infection that could damage liver
Testing revealed the young man had a recent infection with the cytomegalovirus (CMV), which can infect and damage the liver, a condition known as CMV hepatitis. His treating physician identified CMV as a possible contributing factor to the patient’s death, the company stated. No further information concerning the man was released.
DMD is caused by a mutation in the DMD gene that disrupts the production of dystrophin, a protein that provides structural support and protection to muscles. A lack of functional dystrophin leads to progressive muscle damage and, in turn, disease symptoms.
Elevidys contains a gene coding for a micro-dystrophin protein, which works similarly to normal dystrophin but is smaller in size. The therapy is delivered via an infusion into the bloodstream, using a modified AAV known as AAVrh74.
The U.S. Food and Drug Administration granted Elevidys accelerated approval in June 2023 for children with DMD, ages 4 to 5, who have a confirmed DMD gene mutation and can walk. About a year later, the agency expanded its approval, granting the gene therapy traditional approval for DMD patients, ages 4 and older, who can walk and accelerated approval for those in the same age range who can’t walk.
Under accelerated approval, a therapy’s use is allowed based on early evidence of benefit. Further clinical testing with results that support its benefit is required for full approval.
Acute liver injury is among Elevidys’ side effects, and generally resolves
Common side effects of Elevidys seen in clinical trials include nausea, vomiting, fever, and low counts of platelets, which are cell fragments involved in clotting.
Acute liver injury also has been reported in patients treated with Elevidys. Elevated levels of liver damage markers typically are seen within the first eight weeks after the gene therapy is administered.
In clinical trials, most participants with increased markers of liver injury were reported to have no related symptoms, with the markers generally resolving without treatment or with corticosteroids.
Because of these known side effects, Elevidys prescribing label notes that patients with a preexisting liver disease, either chronic or acute — hepatic viral infection is named as an acute disease — may be at higher risk of acute serious liver injury. Liver enzyme tests and liver function monitoring are required before the one-time treatment, and weekly for the first three months thereafter.
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