The Duchenne muscular dystrophy drugs now available only treat the symptoms of the rare muscle-wasting disorder. On Thursday, the FDA approved a Sarepta Therapeutics gene therapy, making it the first treatment that addresses the underlying cause of the inherited disease.

FDA approval of the therapy, Elevidys, covers children ages 4 and 5, which is within the age range during which disease symptoms begin to appear. Those patients must have the ability to walk as well as a confirmed genetic mutation for the disease. Patients must also have no pre-existing medical reason that prevents them from receiving the therapy. Speaking during a conference call Thursday, Sarepta President and CEO Doug Ingram said the company is committed to the clinical research to support broadening of Elevidys’s approval to encompass more Duchenne patients.

“We’re going to expand this label as soon as we are able to and when the science supports that, so we can bring this therapy to patients, first in the United States and then around the world,” he said.

Elevidys is now Sarepta’s fourth approved Duchenne product. Its first three Duchenne treatments belong to a class of medicines called antisense oligonucleotides. Each one addresses only a certain genetic subset of Duchenne patients and these therapies must be taken chronically. The gene therapy is a potential one-time treatment.

Sarepta set a $3.2 million price for Elevidys. Last month, the company published research showing that its gene therapy, compared to the standard of care, would be cost effective priced at $5.1 million. Elevidys is dosed according to a patient’s weight. Ingram said the therapy’s price remains the same if a patient needs more vials to achieve the proper dose.

Duchenne is caused by a mutation to the gene that codes for dystrophin, a protein that helps keep muscle cells intact. Deficiency of this protein leads to progressively worsening muscle weakness that manifests as walking and running difficulty, frequent falls, and fatigue. As the disease progresses, it affects the heart and lungs. Duchenne predominantly affects males, who typically live only into their 20s or 30s before succumbing to heart or respiratory failure.

Elevidys is an engineered version of the gene that codes for dystrophin. It leads to production of a shortened version of dystrophin intended to make up for normal dystrophin that patients lack. The gene therapy is administered as a single intravenous infusion.

Sarepta evaluated Elevidys in open-label studies as well as a randomized, placebo-controlled Phase 2 clinical trial. FDA approval of the gene therapy is based on data from the Phase 2 study, which was conducted in two parts. In the first part, study participants were randomly assigned to receive the experimental therapy or a placebo and were then followed for 48 weeks. In the second part, those who had received a placebo in part one were treated with Elevidys while those who had previously received the therapy were given a placebo. Participants were followed for another 48 weeks.

Results showed that treatment with Elevidys led to increased expression of the micro-dystrophin protein in the 4 to 5 age group. Studies to date have not shown that the gene therapy improves motor function. The FDA decision for Elevidys was made under the accelerated approval pathway, which is intended to increase access to therapies for diseases that have few, if any, available treatments. Accelerated approvals are based on a surrogate endpoint, an indicator that a drug might be working. In the case of the Elevidys study, the surrogate endpoint was the increase in micro-dystrophin levels.

While the most common adverse reactions to Elevidys included vomiting and nausea, some cases of liver injury were also reported in clinical testing. The FDA said patient liver function should be monitored before treatment and weekly for the first three months after dosing. Other risks include inflammation of skeletal and heart muscle, as well as elevation of troponin-I, a heart protein found in the blood following heart muscle injury. The FDA said troponin-I levels should also be monitored before and after dosing of Elevidys.

The new Sarepta gene therapy is not recommended for use in Duchenne patients whose disease is characterized by exon 8 or exon 9 mutations. In clinical trials, complications in such patients were reported that included including severe muscle weakness. The problems were attributed to myositis, a condition in which the immune system attacks muscles.

As a condition of the speedier regulatory nod, Sarepta must confirm patient benefit with additional clinical data. A Phase 3 trial currently underway will serve as Elevidys’s confirmatory study. This trial is designed to assess whether the therapy improves physical function and mobility in Duchenne patients. Sarepta said this study is fully enrolled and preliminary data are expected in the fourth quarter of this year.

The FDA said it will review data from this trial as quickly as possible to determine whether revising the approval or withdrawing it may be necessary.

Photo: Getty Images, Sarah Silbiger