Sarepta Therapeutics has concluded enrollment and dosing in the global Phase III EMERGENE trial, evaluating SRP-9003 (bidridistrogene xeboparvovec), an investigational gene therapy for limb-girdle muscular dystrophy Type 2E/R4 (LGMD2E/R4). This marks a significant step toward a potential disease-modifying treatment for this ultra-rare condition.
The primary endpoint of the EMERGENE trial is the biomarker expression of the beta-sarcoglycan protein, which is critical for muscle function and is deficient in individuals with LGMD2E/R4, also known as beta-sarcoglycanopathy. The study is an open-label, multinational trial that includes both ambulatory and non-ambulatory participants aged four years and older.
Trial Design and Endpoints
The EMERGENE trial is designed to assess the efficacy and safety of SRP-9003 over a 60-month period. Secondary endpoints include functional measures to assess improvements in motor function and quality of life. Safety parameters are also being closely monitored throughout the trial.
SRP-9003 is designed to deliver a full-length beta-sarcoglycan transgene to skeletal, diaphragm, and cardiac muscle using the AAVrh74 vector. This approach aims to restore beta-sarcoglycan protein expression and improve muscle function in patients with LGMD2E/R4.
Regulatory Pathway
Sarepta Therapeutics anticipates submitting a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) for accelerated approval, contingent upon a successful pre-BLA meeting and promising data from the EMERGENE trial. Data from the trial are expected in the first half of next year.
Management Commentary
Louise Rodino-Klapac, Sarepta Therapeutics' Research and Development Head, Executive Vice President, and Chief Scientific Officer, stated, "The completion of enrollment in the EMERGENE study marks a significant milestone to bring a potentially disease-modifying treatment to individuals living with LGMD2E, an ultra-rare form of LGMD with no treatments beyond symptom management."
Rodino-Klapac added, "The design of EMERGENE is an important precedent that informs development plans for Sarepta’s other LGMD pipeline programmes, including our LGMD2D programme, which we just initiated and our LGMD2C programme, which we expect to initiate in the first quarter of 2025, and serves as a pathfinder for heterogeneous neuromuscular gene therapies more broadly."
Previous Studies
In February of the previous year, Sarepta dosed the first participant in the Phase I VOYAGENE trial of SRP-9003 for LGMD2E, marking an earlier step in the clinical development of this gene therapy.
