Sarepta limits US enrollment into Phase 3 DMD trial of SRP-9001

FDA approval decision on gene therapy due this month

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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In the U.S., only a limited number of patients will enter Sarepta Therapeutics‘ ENVISION, a Phase 3 study that’s part of the company’s strategy to gain global approval of SRP-9001 (delandistrogene moxeparvovec) as a gene therapy for Duchenne muscular dystrophy (DMD).

These DMD patients will be non-ambulatory, or unable to walk. Study sites outside the U.S. will enroll both ambulatory (able to walk) and non-ambulatory patients.

The U.S. Food and Drug Administration (FDA) is reviewing an application seeking approval of SRP-9001, initially for children ages 4 to 5 with a genetic diagnosis of DMD who are ambulatory. A final decision is expected this month.

The reason behind Sarepta’s decision to limit ENVISION’s enrollment in the U.S. is the company’s hope that the FDA will consider SRP-9001 for a broader group of patients should there be positive results from EMBARK (NCT05096221), an ongoing Phase 3 study.

If that happens while ENVISION is still in progress, it’s expected that some patients might leave the study if they can get the therapy elsewhere. This could delay the opportunity to make SRP-9001 available to an even broader group of patients in the U.S. and around the world, according to Sarepta.

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Only DMD patients unable to walk can enroll in US

The time frame for U.S. enrollment will be narrow, possibly until mid-autumn. The rest of the study’s participants, estimated at 148 in all, will be enrolled outside of the U.S.

Under Sarepta’s strategy, some study sites may not participate, and interested families may not have the chance to join the study.

“We are enormously thankful for every individual who comes forward to participate in clinical research,” the company wrote in a letter to the U.S. Duchenne community, adding, “We hope that you understand the urgency that shaped this approach, recognizing that the impact of this change may directly affect your family’s hope to join the ENVISION study.”

DMD is a type of muscular dystrophy caused by mutations in DMD, a gene that provides instructions to make a protein called dystrophin. That protein protects muscles and helps them stay strong. The mutations prevent any working dystrophin from being made. As a result, muscles become weak over time.

SRP-9001 uses a harmless virus to deliver a copy of a gene into muscle cells that provides them with instructions for making a shorter, but working, version of dystrophin. It’s given as a single into-the-vein (intravenous) infusion and is expected to improve motor function.

ENVISION (NCT05881408), launching this month, will test how safe SRP-9001 is and how well it works in ambulatory and non-ambulatory boys and men with DMD. The trial will be double-blinded, which means that neither patients nor researchers know who’ll receive SRP-9001 and who’ll be on the placebo.

We hope that you understand the urgency that shaped this approach, recognizing that the impact of this change may directly affect your family’s hope to join the ENVISION study.

Lasting for 128 weeks or nearly 2.5 years altogether, the study will be divided in two parts. During the first part, half of the patients will be randomly assigned to receive a single infusion of SRP-9001 while the other half will receive a matching placebo.

After 72 weeks, or about 1.4 years, the participants will switch groups. This means that during the second part, those who were on the placebo would receive SRP-9001 and vice versa. Participants will be observed for an additional 52 weeks, or one year.

The study is a part of the company’s plan to gain approval for SRP-9001 for as many patients as possible, as quickly as possible. In the U.S., it’s proposed as a confirmatory study to verify the therapy’s clinical benefit in non-ambulatory patients.

Sarepta states that its ability to finish ENVISION successfully will be considered by the FDA when it reports results of EMBARK next year. More details about ENVISION will be provided during a webinar that the Parent Project Muscular Dystrophy will be announcing soon.

The ENVISION trial is expected to be completed in January 2027.