Gene Therapy, Delandistrogene, Provides Functional Improvement in Duchenne Muscular Dystrophy

Across 3 clinical studies with over 80 total participants, treatment with gene therapy delandistrogene (SRP-9001, Sarepta, Cambridge, MA) provided improvements in walking and independent movement as measured with the North Star Ambulatory Assessment (NSAA).

In study 103 of the ENDEAVOR trial (NCT04626674), 20 children age 4 to 7 years with Duchenne muscular dystrophy (DMD), were treated with delandistrogene. After 1 year of treatment, the there was a mean 3.8-point improvement from 22.1 to 26.1 points on the NSAA. In comparison, in a propensity-weighted external control group, mean NSAA score improved by 0.2 points. After adjustment, the least squared mean difference between those treated and those in the control group was 3.8 points (P=.0001). 

Participants treated with delandistrogene also had statistically significant improvement in least squared mean time to rise of 1.2 seconds compared with those in the control group. On the 10-meter walk test, treated children had a least squared mean 1.0 second improvement compared with children in the external control group (P=.002).

In Study 101, 4 children, age 4 to 7, with DMD treated with delandistrogene also had improved independent movement. These children are now all over age 9 years and have experienced a least squared means 9.4-point (least squared means) improvement compared with a propensity-weighted external control group (P=.013). In the natural history of DMD, many children are losing their mobility.

In integrated analysis of these 2 studies and a placebo-controlled cohort of 28 children with DMD, those treated with delandistrogene for 1 year had a least squared mean improvement of 2.4 points on NSAA compared with those in the control group (P<.0001)

“We are absolutely delighted by these most recent results. We now have positive results across multiple studies and multiple time points, including 1-, 2- and 4-years after treatment, and are very pleased with the consistent safety profile across more than 80 treated patients,” said Doug Ingram, president and chief executive officer, Sarepta.

“In Study 103, we continue to see statistically significant improvements in NSAA scores and timed function tests for SRP-9001-treated patients from baseline and when compared to a propensity-weighted external control group. With the progressive nature of this disease, what has been particularly gratifying is seeing these treatment effects increase over time compared to the external control, as well as the maintenance of ability in older patients who would otherwise be declining,” said Louise Rodino-Klapac, PhD, executive vice president and chief scientific officer, Sarepta. “We’re excited to share these data more broadly in the coming months, particularly with the Duchenne community. We are grateful to the patients, families, investigators and site teams, whose support has been critical to the advancement of this program.”

Vomiting was the most common treatment-related adverse event. Elevation of liver enzymes was transient and responsive to steroid treatment. A single child, treated when over age 8, had a serious case of myocarditis without symptoms of systolic dysfunction treated with intravenous methylprednisolone and other chronic cardiac medication. Normal function was seen on cardiac MRI 1 month later with partial resolution of myocarditic changes. Normal systolic function was seen on echocardiogram 4 months after the event. 

These data were presented at the International Congress on Neuromuscular Diseases (ICNMD) in Brussels, Belgium.