SRP-9001 for DMD

Last updated June 29, 2022, by Teresa Carvalho, MS

✅ Fact-checked by José Lopes, PhD

What is SRP-9001 for DMD?

SRP-9001 is a gene therapy candidate to improve motor function in people with Duchene muscular dystrophy (DMD).

The treatment is being developed by Sarepta Therapeutics, but was initially investigated by the Nationwide Children’s Hospital. Roche holds the exclusive right to launch and commercialize SRP-9001 outside the United States.

The U.S. Food and Drug Administration granted SRP-9001 orphan drug, fast track and rare pediatric disease designations, all intended to support its clinical development and testing. The treatment has also been granted orphan drug status in Europe and Japan.

How does SRP-9001 work in DMD?

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. Several DMD mutations have been reported, and the majority result in no production of functional dystrophin. This affects muscle integrity and leads to their progressive breakdown.

The DMD gene is the largest in the human genome. SRP-9001 is designed to deliver a gene coding for a so-called micro-dystrophin protein, which works similarly to normal dystrophin, albeit at a smaller size. The therapy uses a harmless, modified virus (AAVrh74) that has a high affinity for muscle tissue, allowing for targeted delivery. Moreover, it 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.

How is SRP-9001 administered?

A single dose of SRP-9001 is administered by an intravenous (into-the-vein) infusion. In clinical trials, patients received SRP-9001 at a dose of 2.0×1014 vector genomes per kilogram bodyweight (vg/kg).

SRP-9001 in clinical trials

All clinical trials assessing SRP-9001 in patients with DMD are currently ongoing. Promising preliminary data from these studies have been published.

Study 101

Study 101 is an ongoing Phase 1/2 trial (NCT03375164) evaluating the safety, effectiveness, and tolerability of a single dose of SRP-9001 administered into the bloodstream of boys with DMD. The study also is testing participants’ muscle function. Muscle biopsies before treatment and 90 days post-therapy will be used to assess micro-dystrophin levels in the muscles. Six patients, ages 3 months to 3 years, were included in one group, while the second group consisted of six participants, ages 4 to 7 at enrollment.

According to preliminary results from four patients, SRP-9001 enhanced the activity of micro-dystrophin in muscle fibers. A muscle biopsy showed high levels of micro-dystrophin, as 81.2% of muscle fibers had the therapeutic protein after treatment. Blood levels of creatine kinase, a marker of muscle damage, was 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 test, and the North Star Ambulatory Assessment (NSAA), a standard measure of motor function in ambulant children with DMD. All four boys fared better in the tests 90 days after treatment compared with the baseline.

The study also found that those four patients had an improvement in NSAA scores by 8.6 points three years after being given SRP-9001 compared with those in a natural history study. A natural history study follows disease course in the absence of therapy.

Study 102

A Phase 2 trial (NCT03769116) enrolled 41 DMD patients between ages 4 and 7 to evaluate the safety and effectiveness of infusions of SRP-9001. The trial is divided in three parts. The first two parts are designed to last 48 weeks (almost one year).

Part one is aimed at monitoring changes in micro-dystrophin levels in the body as well as the NSAA score. Results from this first part of the trial showed that patients who received SRP-9001 achieved a mean micro-dystrophin activity of 28.1% after 12 weeks of treatment. There also was a significantly greater improvement in the total NSAA score among boys ages 4 to 5 who were treated with SRP-9001, compared with those with 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 compared with matched patients in a natural history group.

In the second part of the study, patients who were assigned to a placebo in the first part were given SRP-9001 and assessed by similar measures. Trial results showed patients treated with SRP-9001 had an average of 2 points higher in their NSAA score compared to an external group of patients, matched for variables including age and steroid usage. Particularly, the SRP-9001-treated group increased its NSAA score by 1.3 points while controls had a 0.7-point decrease.

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

Study 103 (ENDEAVOR trial)

An open-label trial called ENDEAVOR (NCT04626674) is evaluating the safety of a single dose infusion of SRP-9001 in 20 boys ages 4 to 7 and 12 older patients, both able or unable to walk. 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 in this trial showed a significant 3-point improvement in the NSAA six months after treatment, compared with their pre-treatment results.

EMBARK trial

A Phase 3 clinical trial called EMBARK (NCT05096221) is currently recruiting males with DMD ages 4 to 7 at several locations in the U.S. and abroad to assess the safety and efficacy of SRP-9001. Patients will be randomly assigned to receive a single infusion of the gene therapy or placebo over a year. Then, participants initially given SRP-9001 will receive placebo, and vice versa, and be followed for another year. Changes in NSAA are the main goal of this study.

Common side effects of SRP-9001

The most common treatment-related side effect observed in clinical trials was vomiting, usually within the first weeks after the infusion. Some patients have also experienced:

  • an increase in a marker of liver damage, which was resolved with steroid treatment
  • rhabdomyolysis, a serious complication of muscle tissue breakdown


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