Groundbreaking Gene Therapy for Limb-Girdle Muscular Dystrophy Shows Promising 5-Year Safety Profile

In a remarkable advancement for the treatment of limb-girdle muscular dystrophy 2E/R4 (LGMD2E/R4), new data from a phase 1/2 clinical trial has showcased the long-term safety of bidridistrogene xeboparvovec, an investigational gene therapy developed by Sarepta Therapeutics. The findings indicate that the gene therapy maintains a solid safety profile for patients over a follow-up period of 4 to 5 years, raising hopes for individuals affected by this debilitating condition.

Presented during the 2025 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference in Dallas, Texas, this analysis focused on a small group of six patients. These individuals were split into two cohorts, each receiving a single intravenous dose of bidridistrogene xeboparvovec—one receiving 1.85x10^13 vg/kg and the other 7.41x10^13 vg/kg. Remarkably, 25 treatment-related adverse events (TR-TEAEs) were reported, primarily mild to moderate in severity and occurring mostly within the first 90 days post-treatment. Side effects included vomiting and elevated liver enzymes; however, all severe cases, such as acute liver injury and dehydration, were successfully managed through clinical interventions.

Conducted under the guidance of neuromuscular specialist Dr. Jerry Mendell, the trial enrolled patients aged between 4 and 15 years who had specific gene mutations and were free of antibodies against the adeno-associated virus serotype rh74 (rAAVrh74). The innovative gene therapy, also known as SRP-9003, utilizes an AAVrh74 vector designed to deliver a functional beta-sarcoglycan (SGCB) transgene, crucial for repairing muscle cell function. This is exceptionally significant as many patients suffering from LGMD2E typically face serious cardiac and pulmonary complications.

The spotlight now shifts to the ongoing phase 3 study called EMERGENE, which aims to solidify the therapy's safety and efficacy for potential accelerated approval. Targeting both ambulatory and non-ambulatory patients aged 4 and older, the trial will measure changes in SGCB expression at 60 days as its primary outcome. More than 100 patients have been enrolled, with diverse functional assessments and safety measures planned over 60 months.

Interim results from the earlier trial phase were previously highlighted in *Nature Medicine* in early 2024, announcing significant SGCB expression levels of 36.2% and 62.1% for the respective cohorts after 60 days. Additionally, reductions in serum creatine kinase (CK) levels were observed, suggesting improvements in muscle function. These compelling metrics hint at the potential of bidridistrogene xeboparvovec to revolutionize the treatment landscape for LGMD2E patients.

As healthcare enthusiasts eagerly await the full results of this promising therapy, many remain hopeful that gene therapy like bidridistrogene xeboparvovec can provide a new lease on life for those battling limb-girdle muscular dystrophy. Further investigations into the effectiveness and long-term impact of this therapy may pave the way for breakthroughs that redefine treatment for rare muscular disorders.