FDA OKs trial of SRP-9005 gene therapy for LGMD type 2C
Sarepta says trials of 2 other LGMD treatments progressing
The U.S. Food and Drug Administration (FDA) has cleared Sarepta Therapeutics to start dosing and screening in a first clinical trial testing the gene therapy SRP-9005 in people with limb-girdle muscular dystrophy type 2C (LGMD2C).
Sarepta said advancement continues for SRP-9003 and SRP-9004, two gene therapies already in clinical testing for other types of LGMD.
“There are no disease-modifying treatments approved for patients with any subtype of limb-girdle muscular dystrophy, and the unmet medical need is significant,” Louise Rodino-Klapac, PhD, executive vice president, chief scientific officer, and head of research and development at Sarepta, said in a company press release. SRP-9005 is “the fourth LGMD program that Sarepta has advanced into the clinic,” Rodino-Klapac said.
LGMD refers to a group of genetic disorders characterized by muscle weakness that mainly affects muscles in the hips and shoulders. There are several different types of LGMD, each caused by a different type of underlying mutation.
LGMD2C, also known as LGMDR5 or gamma-sarcoglycanopathy, is caused by mutations in the SGCG gene. SRP-9005 is designed to deliver a healthy version of this gene to muscle cells, including those of the heart. Heart and breathing problems are a leading cause of mortality in LGMD2C.
Targeting LGMD through gene therapy
Sarepta did not provide details about when the planned clinical trial, called COMPASS, will begin recruitment, or about the study’s design.
Sarepta’s other LGMD gene therapies include SRP-9003, which aims to treat LGMD type 2E (LGMD2E), and SRP-9004, designed to treat LGMD type 2D (LGMD2D). Like SRP-9005, these gene therapies aim to deliver to muscle cells a healthy version of the gene whose mutation causes each of these types of LGMD.
All three gene therapies use the same vector, called AAVrh74, to deliver their genetic payloads. AAVrh74 is a modified version of a virus that’s been engineered to deliver a therapeutic gene instead of causing infection.
SRP-9004 is being tested in the proof-of-concept Phase 1 DISCOVERY trial (NCT06747273) which is testing the therapy in about four people with LGMD2D, with the main goal of assessing safety. According to Sarepta, all participants have been enrolled and dosed. The company did not say when results are expected.
Enrollment and dosing has also finished for a Phase 3 study called EMERGENE (NCT06246513) that’s testing SRP-9003 in 17 people with LGMD2E. This trial’s main goal is to ascertain whether SRP-9003 can effectively lead to expression of beta-sarcoglycan, the muscle protein that is deficient in people with this type of LGMD. Results are expected in the first half of this year.
If results from EMERGENE are positive, Sarepta plans to use the trial as a basis to ask the FDA to grant accelerated approval to SRP-9003. Accelerated approval is a type of conditional approval in which the FDA allows a treatment to be marketed based on clinical data suggesting the therapy will likely benefit patients, while still requiring the treatment’s developer to conduct additional testing to prove clinical benefit. Sarepta said it is on track to submit an application seeking accelerated approval of SRP-9003 in the second half of 2025.
“Our confidence in the potential for gene therapy to bring meaningful treatments to patients with rare, genetic based diseases remains high and the rapid progress across our LGMD pipeline is encouraging,” Rodino-Klapac said.
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