First Gene Therapy to Treat Pediatric Duchenne Muscular Dystrophy Approved by FDA


The accelerated approval of delandistrogene moxeparvovec-rokl is “based on expression of Elevidys micro-dystrophin observed in patients treated with ELEVIDYS,” according to Sarepta Therapeutics.

The FDA has approved delandistrogene moxeparvovec-rokl (ELEVIDYS; Sarepta Therapeutics, Inc) to treat ambulatory pediatric patients aged 4 to 5 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene.1 The approval makes delandistrogene moxeparvovec-rokl the first gene therapy to treat this patient population.2

The indicated accelerated approval of delandistrogene moxeparvovec-rokl is “based on expression of Elevidys micro-dystrophin observed in patients treated with ELEVIDYS,” per a press release from Sarepta Therapeutics. Continued approval could be “contingent upon verification and description of clinical benefit in confirmatory trial(s).”1

Duchenne muscular dystrophy, a rare genetic condition that worsens over time, leads to the “weakness and wasting away of the body’s muscles,” according to a press release from the FDA. The disease occurs because of a defective gene resulting in the absence of dystrophin, a protein that helps keep the body’s muscle cells intact. Those with DMD can have symptoms like trouble with walking and running, frequent falls, learning disabilities or difficulties, fatigue, heart issues (due to impact on heart muscle functioning), and breathing problems (because of weakening respiratory muscles that involve lung function.)2

Symptoms associated with DMD generally start in childhood between 3 to 6 years, mainly affecting males, and in rare cases, females. Approximately 1 in every 3300 boys are affected by the disorder, which can present life-threatening heart and respiratory problems as it progresses. Due to heart and/or respiratory failure, individuals with DMD “succumb to the disease in their 20s or 30s,” though disease severity and life expectancy varies.2

Delandistrogene moxeparvovec-rokl, a recombinant gene therapy, is administered as a single intravenous dose. The product is designed to deliver a gene into the body that leads to the production of Elevidys micro-dystrophin, “a shortened protein (138 kDa, compared to the 427 kDa dystrophin protein of normal muscle cells) that contains selected domains of the dystrophin protein present in normal muscle cells,” according to Sarepta.2

“Duchenne is a relentlessly progressive, degenerative disease, robbing children of muscle function,” said Jerry Mendell, MD, pediatric neurologist and principal investigator, Center for Gene Therapy at Nationwide Children’s Hospital. “The increases in ELEVIDYS dystrophin expression and the functional results that we see can make a difference in the lives of our patients.”1

According to Sarepta, the accelerated approval is “based on an increase in ELEVIDYS micro-dystrophin protein expression in skeletal muscle,” and is supported by “biologic and empirical evidence, in addition to efficacy data from two clinical studies: SRP-9001-102 and SRP-9001-103 and safety data from SRP-9001-101, SRP-9001-102 and SRP-9001-103.”1

The approval follows data from a randomized clinical trial establishing that delandistrogene moxeparvovec-rokl increased the expression of the Elevidys micro-dystrophin protein observed in delandistrogene moxeparvovec-rokl-treated patients aged 4 to 5 years with DMD. The FDA concluded data demonstrated that an increase in expression of Elevidys micro-dystrophin “is reasonably likely to predict clinical benefit in individuals 4 to 5 years of age with DMD who do not have significant pre-existing antibody titers against the AAV rh74 vector or have other contraindications based on the inclusion criteria of the clinical trials.” The agency considered the potential risks associated with the drug, the unmet medical need, and the nature of the disease for the children affected.2

Vomiting, nausea, acute liver injury, pyrexia, and thrombocytopenia were the most common adverse reactions for individuals who received delandistrogene moxeparvovec-rokl in clinical trials. Liver function of patients treated with delandistrogene moxeparvovec-rokl should be monitored before treatment and for 3 months after treatment on a weekly basis. Patients could also be at risk for severe immune-mediated myositis. Myocarditis and elevated troponin-I, a heart protein found in the blood after a heart muscle injury, have been observed in individuals treated with delandistrogene moxeparvovec-rokl in clinical trials. Before treatment and weekly for 1 month after treatment, troponin-I levels should be monitored.2

According to Sarepta, delandistrogene moxeparvovec-rokl “is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the DMD gene.”1

This article originally appeared on Contemporary Pediatrics.

1. Sarepta Therapeutics announces FDA approval of ELEVIDYS, the first gene therapy to treat Duchenne muscular dystrophy. News Release. Sarepta. Therapeutics. June 22, 2023. Accessed June 22, 2023.
2. FDA approves first gene therapy for treatment of certain patients with Duchenne muscular dystrophy. News Release. FDA. June 22, 2023. Accessed June 22, 2023.
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