Elevidys (delandistrogene moxeparvovec-rokl) for Duchenne muscular dystrophy

Last updated Sep. 6, 2023, by Marisa Wexler, MS
Fact-checked by José Lopes, PhD

What is Elevidys for Duchenne muscular dystrophy?

Elevidys (delandistrogene moxeparvovec-rokl), previously called SRP-9001, is a one-time gene therapy approved in the U.S. to treat certain patients with Duchenne muscular dystrophy (DMD).

It was developed by Sarepta Therapeutics, but was first investigated by researchers at the Nationwide Children’s Hospital. Roche holds the exclusive right to launch and market Elevidys outside the United States.

The U.S. Food and Drug Administration (FDA) granted Elevidys accelerated approval in June 2023, making it the first gene therapy for DMD to be authorized for commercial use. The accelerated approval pathway lets the FDA grant early approval to therapies based on clinical biomarker data that suggest they’re likely to be effective.

Elevidys was approved based on data showing it leads to the expression of micro-dystrophin protein in patients’ muscles, suggesting it works as designed. Clinical trials to evaluate if and how treatment affects the progression of DMD are still ongoing, and as with all therapies granted accelerated approval, continued approval of Elevidys depends on positive results in clinical testing.

Therapy snapshot

How does Elevidys work?

DMD is caused by a mutation in the DMD gene that carries the instruction to make dystrophin, a protein that provides structural support and protection to muscles. DMD-causing mutations result in no functional dystrophin being produced, leading to the progressive muscle damage that gives rise to disease symptoms.

The DMD gene is the largest in the human genome. Elevidys is designed to deliver a gene coding for what’s called an Elevidys micro-dystrophin protein, which works similarly to normal dystrophin, albeit at a smaller size.

The therapy uses a harmless modified virus, known as AAVrh74, that has a high affinity for muscle tissue, allowing for targeted delivery. It also has a muscle-specific promoter — a DNA element that controls the activity of a gene — called MHCK7, intended to enhance the gene’s activity in cardiac and skeletal muscles.

Who can use Elevidys?

Elevidys was approved by the FDA in 2023 for children with Duchenne, ages 4 to 5, who have a confirmed mutation in the DMD gene and are able to walk. Clinical trials evaluating the therapy in broader patient populations are ongoing.

Who should not use Elevidys?

Elevidys should not be administered to people with DMD who have deletion mutations involving exon 8 and/or exon 9 in the DMD gene. Exons are the coding sections that have the information to produce proteins. There are 79 exons in the DMD gene.

It’s also not recommended for patients with significant levels of preexisting antibodies against the AAVrh74 viral vector that’s used in the therapy.

How is Elevidys administered?

Elevidys is administered via an infusion into the bloodstream over one to two hours. It’s given at a dosage of 133 trillion vector genomes per kilogram of body weight.

One day before administering Elevidys, patients should start on a regimen of corticosteroids to reduce the risk of an immune response. For those already taking corticosteroids, higher doses are given. The corticosteroid should be continued for at least 60 days and should then be tapered off over several weeks.

Before administering Elevidys, patients should be evaluated to assess liver function markers, platelet counts, and troponin-I (a marker of heart damage) levels.

It shouldn’t be administered to someone with an active infection. If a patient has an active infection then the infusion should be postponed until it resolves.

Elevidys in clinical trials

The FDA’s approval of Elevidys was based on three clinical trials. One has been completed; the other two are ongoing.

Study 101

Study 101 is a completed Phase 1/2 trial (NCT03375164) that evaluated the safety, effectiveness, and tolerability of a single dose of Elevidys administered into the bloodstream of boys with DMD, ages 4-7 at enrollment.

According to preliminary results from four patients, Elevidys enhanced the levels of micro-dystrophin in muscle fibers. A muscle biopsy showed high levels of micro-dystrophin, with 81.2% of muscle fibers having the therapeutic protein after treatment. Blood levels of creatine kinase, a marker of muscle damage, were reduced by more than 78%. Motor function was measured using four different tests, which include time to rise, time to climb four stairs, the 100-meter walk, and the North Star Ambulatory Assessment (NSAA), a standard measure of motor function in DMD children who are able to walk. All four boys fared better in the tests 90 days after treatment compared with the baseline.

The study also found that the four patients had an improvement in NSAA scores by 8.6 points three years after being given Elevidys compared with those in a natural history study. A natural history study follows a disease course in the absence of therapy.

At four years after treatment, the average NSAA score improved by 7 points with Elevidys. Patients from an external group who didn’t receive the therapy saw a worsening of more than 3 points over a similar time as the disease progressed. The difference between the groups was more than 9 points.

Study 102

A Phase 2 trial (NCT03769116) enrolled 41 DMD patients between the ages 4 and 7 to evaluate the safety and effectiveness of Elevidys. The trial is divided in three parts. The first two parts are designed to last 48 weeks (almost one year).

The first part is aimed at monitoring changes in micro-dystrophin levels as well as the NSAA score. Results from this part showed that patients who received Elevidys achieved a mean micro-dystrophin activity of 28.1% after 12 weeks. There also was a significantly greater improvement in the total NSAA score among boys ages 4 to 5 with Elevidys, compared with those at this age in the placebo group.

The study also found changes in NSAA scores of treated boys at ages 6 and 7. These patients showed a 2.9-point improvement from baseline at 48 weeks over matched patients in a natural history group.

At two years after gene therapy, the average NSAA score among all boys treated with Elevidys in the first part of the study improved by 1.6 points. This contrasted with worse NSAA scores in an external untreated group, reflecting gradual worsening of motor function.

In the study’s second part, patients who were assigned to a placebo in the first part were given Elevidys and assessed by similar measures. Trial results showed those treated with Elevidys had a NSAA score that was an average of 2 points higher than an external group matched for variables including age and steroid use. Particularly, the Elevidys-treated group increased its NSAA score by 1.3 points, while controls saw a 0.7-point decrease.

In Part 3, patients will enter an open-label extension. The trial is expected to end April 2026.

ENDEAVOR trial

An open-label trial called ENDEAVOR (NCT04626674) is evaluating the safety of a single-dose infusion of Elevidys in 20 boys ages 4 to 7 and 12 older patients, both able or unable to walk. The patients are being followed for five years. The trial’s primary goal is changes in micro-dystrophin protein levels from the study start to 12 weeks. Exploratory measures include changes in motor skills.

Data from the first 11 boys treated showed a significant 3-point improvement in NSAA score six months after treatment over the pretreatment results. In the 20 boys able to walk, The improvement was 4 points at one year. Further improvements were found in the time the boys took to get up from a lying position to walking 10 meters (almost 33 feet). Micro-dystrophin protein was being produced as designed at this timepoint, analyses showed.

EMBARK trial

A Phase 3 clinical trial called EMBARK (NCT05096221) is assessing the safety and effectiveness of Elevidys in male patients with DMD ages 4-7. The patients will be randomly assigned to receive a single infusion of the gene therapy or placebo over a year. Then, participants initially given Elevidys will receive a placebo and vice versa and will be followed for another year. Changes in NSAA are the main goal.

EMBARK is the post-marketing confirmatory study whose results are key for the continued approval of Elevidys. Assuming the results from EMBARK are positive, they will form the basis of a request to expand the approved label, Sarepta said.

ENVISION trial

The Phase 3 ENVISION trial (NCT05881408) will evaluate Elevidys in a broader population of DMD patients than other trials. It’s open to male patients of all ages who are both ambulatory and nonambulatory, though sites in the U.S. will only recruit patients who can’t walk.

Patients in this trial will receive a single infusion of Elevidys or a placebo and then followed for 72 weeks (about 1.5 years). After this, those initially given Elevidys will receive placebo and vice versa. The study’s main goal is to assess the impact of treatment on arm and hand function using a standardized measure called Performance of Upper Limb (PUL).

Common side effects of Elevidys

The most common side effects of Elevidys seen in clinical trials include:

• vomiting
• nausea
• fever
• thrombocytopenia (low counts of platelets, which are cell fragments involved in clotting)
• increased markers of liver damage.

Liver injury

Acute, serious liver injury has been reported in patients given Elevidys. Elevated levels of liver damage markers are usually seen within the first eight weeks after the gene therapy is given.

In clinical trials, most patients with increased markers of liver damage didn’t have any symptoms of liver injury and markers of liver injury generally resolved without the need for treatment or with corticosteroids. No cases of liver failure were reported.

Muscle inflammation

Myositis, or muscle inflammation, has been reported in patients given Elevidys, with some cases being severe or life-threatening. The risk of severe myositis is especially high among those with deletion mutations involving exon 8 and/or exon 9 in the DMD gene, which is why Elevidys shouldn’t be given to patients with these mutations.

A risk of myositis also may exist for those with mutations in other regions of the DMD gene, including mutations in exons 1 to 17 and/or exons 59 to 71, but limited data are available to assess this risk.

If a patient given Elevidys begins to have symptoms of possible myositis — such as increased muscle pain, tenderness, or weakness, including difficulty swallowing, speaking, or breathing — medical experts should be contacted immediately. Immune-suppressing therapies may help control myositis if it occurs.

Heart inflammation

Acute serious myocarditis (inflammation of the heart muscle) has been reported with Elevidys. Levels of the heart damage marker troponin-I should be checked before gene therapy treatment, then monitored weekly for at least the first month after.

Patients given Elevidys who encounter heart symptoms like chest pain or difficulty breathing should contact their healthcare team immediately. More frequent heart monitoring may be warranted with these symptoms.

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