Sarepta Reports Positive Phase 3 Data for AAV Gene Therapy SRP-9003 in LGMD Trial

VIENNA, AUSTRIA — October 20, 2025- Sarepta Therapeutics announced promising top-line results for its investigational gene therapy, SRP-9003 (bidridistrogene xeboparvovec), demonstrating robust production of the deficient protein in patients with limb-girdle muscular dystrophy Type 2E (LGMD2E/R4). The data, presented at the 30th annual International Congress of the World Muscle Society (WMS) held from October 7-11, showed the therapy successfully met its primary endpoint in the Phase 3 EMERGENE clinical trial (NCT06246513).

The AAV vector-based therapy is designed to deliver the gene for the β-sarcoglycan protein (β-SG), which is missing in LGMD2E patients.

Successful Protein Restoration and Biomarker Response

The EMERGENE trial included two cohorts: 11 ambulatory patients and 6 nonambulatory patients.

• Primary Endpoint Met (Ambulatory Patients): The primary endpoint was successfully met in the ambulatory cohort, showing a mean 43.4% change from baseline (CFBL) in $\beta$-SG expression at day 60, as measured by percent positive fibers (PPF) ($P < .001$).
• Nonambulatory Response: The nonambulatory cohort also showed a positive response, with a mean 23.9% CFBL in $\beta$-SG expression by PPF ($P < .02$).
• Consistent Findings: Secondary measures confirmed the robust expression: ambulatory patients achieved a mean 18.23% CFBL via percent fluorescent intensity (PFI) and 33.58% CFBL via Western blot. Crucially, the study also observed colocalization and restoration of the entire sarcoglycan protein complex ($\beta$-SG and $\delta$-SG).
• Disease Biomarker Reduction: Further indicating a positive biological effect, patients saw a dramatic drop in muscle damage markers. Mean serum creatine kinase (CK) levels dropped by -88.8% in the ambulatory cohort and -92.4% in the nonambulatory cohort by day 60.

First author Anne M. Connolly, MD, commented on the findings, writing: “These findings demonstrate robust expression of $\beta$-SG at 60 days post treatment along with restoration of other component proteins… The findings indicate that bidridistrogene xeboparvovec treatment induces a biological cascade likely to predict clinical benefit.”

Safety Profile

The overall safety of SRP-9003 was characterized as “manageable with appropriate monitoring.” The most common treatment-emergent adverse events (TEAEs) were gastrointestinal, including nausea (70.6%), decreased appetite (47.1%), and vomiting (41.2%).

However, the trial also reported TEAEs associated with acute liver injury. As of the data cut, seven patients (41.2%) experienced these events, including five Grade 2-3 cases in the ambulatory cohort. Four additional Grade 1 cases were noted after the data cut. Importantly, the acute liver injuries observed were not deemed treatment-related, and no treatment-related deaths were reported in the trial.

The gene therapy uses the rAAVrh74 viral vector, a platform recently involved in regulatory scrutiny. Sarepta was initially granted the FDA’s new platform technology designation for the rAAVrh74 vector, which is also used in its approved Duchenne muscular dystrophy therapy, Elevidys, and its investigational therapy SRP-9004.