Sarepta’s gene therapy Elevidys misses primary goal in phase 3 DMD trial

Despite not reaching statistical significance on the trial’s primary endpoint, Sarepta’s president and CEO Doug Ingram pointed to promising results in the trial’s secondary endpoints as evidence that the therapy could still be effective in this patient population.

DMD is caused by a mutation in the DMD gene, leading to muscle weakness and degeneration. Administered in a single dose, Elevidys is designed to deliver a therapeutic gene that brakes the muscle degeneration process.

The gene therapy was granted accelerated approval by the U.S. Food and Drug Administration (FDA) earlier this year and is currently indicated for the treatment of DMD in ambulatory pediatric patients aged 4 through 5 years with a confirmed mutation in the DMD gene. The latest trial, named EMBARK, was part of Sarepta’s attempt to expand the indication of Elevidys to more children with DMD.

EMBARK tested the benefits of Elevidys by measuring patients’ functional motor abilities on a scale called the North Star Ambulatory Assessment (NSAA). In the topline results, patients treated with Elevidys saw a 2.6 percentage point improvement in their NSAA one year after receiving the therapy. This wasn’t statistically greater than the 1.9 percentage point improvement in patients given a placebo.

Strongest predictor of early loss of ambulation

However, statistical significance was reached in secondary endpoints across age groups, such as time to rise and a 10-meter walk test.

“Passing 5 seconds on time to rise is the strongest predictor of early loss of ambulation and in EMBARK, Elevidys reduced those odds over 52 weeks by greater than 90 percent,” said Sarepta’s president and CEO Doug Ingram in a public statement​.

Ingram added that Sarepta expects to request a label expansion based on the trial results. “Importantly, we have shared the EMBARK topline results with FDA leadership and they have confirmed that, based on the totality of the evidence, they are open to such label expansion if supported by review of the data, and that they intend to proceed rapidly with consideration of the submission,” he stated.

In addition to Elevidys, Sarepta markets three antisense oligonucleotide therapies that can be injected weekly to correct mutations in different forms of DMD. The company is also developing RNA targeted therapies, gene therapies and gene edited therapies for DMD and other rare diseases such as limb-girdle muscular dystrophy type 2E/R4 (LGMD2E/R4).