#MDA2022 – DMD Boys Show Benefits of SRP-9001 Gene Therapy After 3 Years

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

SRP-9001 gene therapy | Muscular Dystrophy News | illustration for MDA 2022 conference

Four boys with Duchenne muscular dystrophy (DMD) show improved motor function and walking ability three years after being given the experimental gene therapy SRP-9001 in a Phase 1 clinical trial, new data reveal.

The findings were presented in a poster, titled “Phase 1/2A Trial of Delandistrogene Moxeparvovec (SRP-9001) in Patients with Duchenne Muscular Dystrophy: 3-year Safety and Functional Outcomes,” at the Muscular Dystrophy Association (MDA) 2022 Annual Meeting.

In DMD, mutations render the body unable to produce dystrophin, a protein vital for maintaining the health of muscle cells. Sarepta Therapeutics’ therapy SRP-9001 (delandistrogene moxeparvovec) is designed to deliver a gene encoding micro-dystrophin — a shortened but functional version of the dystrophin protein — to the body’s muscle cells by using a harmless viral vector called adeno-associated virus.

Recommended Reading
A DNA strand is shown.

#MDA2022 – DMD Gene Therapy PF-06939926 Safe at High Dose: Trial

Sarepta is sponsoring a proof-of-concept Phase 1/2 study called Study 101 (NCT03375164) to test SRP-9001’s safety and efficacy in four boys with DMD, who were from 4 to 6 years old when they were given the single dose.

All four boys have been in the trial now for at least three years. To date, there have been no serious safety-related events or any discontinuations.

Treatment side effects generally occurred within a few weeks of being dosed with SRP-9001, with vomiting being the most common side effect. Three patients experienced an increase in a marker of liver damage, which was resolved with steroid treatment and did not cause noticeable symptoms. No new side effects of treatment have been reported in years two or three of the study.

Three years after their treatment, all four boys showed a marked improvement in scores on the North Star Ambulatory Assessment (NSAA), a measure of motor function in DMD. Their scores increased by a mean of 7.5 points.

The boys are currently between the ages of 7 and 9. Natural history data (the disease’s course in the absence of treatment) suggest that NSAA scores usually increase over time in DMD boys up to about age 6, and then they gradually worsen over time as the disease progresses.

The time it took patients to climb up four stairs, or to stand from the floor, generally did not change over three years after SRP-9001 treatment, which indicates that “patients generally maintained muscle strength,” the researchers wrote.

Walking ability, as measured by the time it took participants to walk 100 meters (328 feet), improved after three years in all three patients with evaluable data (the fourth could not be evaluated at three years due to logistical problems stemming from the COVID-19 pandemic). The time it took to walk this distance decreased by a mean of over 10 seconds — this contrasts with the natural history data, which predicted that patients would take longer to walk this distance.

“Motor improvements in the NSAA scale were generally associated with improvements in ambulation over 3 years … compared with the decline generally expected in untreated natural history patients,” the researchers concluded.

“The safety profile and durable response in Study 101 provides proof-of-concept support for the continuation of clinical trials to assess [SRP-9001] in patients with DMD,” they added.

Recommended Reading
LGMD | Muscular Dystrophy News | announcement illustration of woman with megaphone

LGMD Gene Therapy ATA-100 Wins Orphan Drug Status From FDA, EMA

Sarepta is currently conducting a Phase 3 clinical trial called EMBARK (NCT05096221) to further evaluate the safety and efficacy of SRP-9001 in DMD. The trial is recruiting male participants, ages 4 to 7, at 10 sites in the U.S.

Study participants will be given a single infusion of the gene therapy or a placebo, and will then be monitored for a year. At that point, participants originally given SRP-9001 will get an infusion of placebo, and vice versa, followed by an additional year of monitoring. The study’s main goal is to evaluate the effect of treatment on NSAA scores.

Recent data from a Phase 2 clinical trial called Study 102 (NCT03769116), which followed a similar design, indicated that treatment with SRP-9001 benefited patients originally given the gene therapy as well as those who received the gene therapy later on, after they originally got placebo.


Note: The Muscular Dystrophy News Today team is providing coverage of the 2022 MDA Clinical and Scientific Conference March 13–16. Go here to see the latest stories from the conference.