Sarepta Perseveres with Gene Therapy for LGMD Despite Regulatory Hurdles

Sarepta Therapeutics, a biotech company known for its gene therapy programs, is pushing forward with its investigational treatment for limb-girdle muscular dystrophy (LGMD) despite recent setbacks and a strategic pivot towards siRNA therapeutics. The company presented promising late-stage data for its gene therapy candidate SRP-9003 at the 30th annual International Congress of the World Muscle Society (WMS) in Vienna, Austria, demonstrating the treatment's potential efficacy while navigating complex regulatory challenges.

SRP-9003 Shows Promise in Phase III EMERGENE Study

The Phase III EMERGENE study, which included 17 LGMD patients, revealed that SRP-9003 met its primary endpoint. Non-ambulatory patients experienced a 23.9% average increase in beta-sarcoglycan protein expression, a crucial biomarker for muscle structure and function. In ambulatory patients, the increase was even more pronounced at 43.4%.

Safety data from the trial was particularly scrutinized following earlier patient deaths associated with Sarepta's gene therapy platform. While over 40% of patients showed signs of acute liver injury, none of these adverse events were deemed related to SRP-9003, offering a glimmer of hope for the treatment's safety profile.

Regulatory Challenges and Strategic Decisions

Despite the encouraging data, SRP-9003 faces significant regulatory hurdles. The FDA has placed a clinical hold on all of Sarepta's LGMD gene therapy programs, citing "unreasonable and significant risk of illness or injury" to study participants. This decision followed three patient deaths linked to Sarepta's gene therapy platform, including its Duchenne muscular dystrophy treatment Elevidys.

The regulatory setback has led analysts to reevaluate the probability of success for SRP-9003. Jefferies analyst Andrew Tsai noted that their previous 75% probability of success rating has declined, while Andy Chen of Wolfe Research stated they "assign no value to 9003 in our model given extreme FDA uncertainty."

Sarepta's Commitment to LGMD Patients

Despite these challenges, Sarepta remains committed to advancing SRP-9003, particularly for patients with LGMD 2E, a severe subtype caused by mutations in the beta-sarcoglycan gene. The company's decision to continue development is driven by both financial considerations and a sense of obligation to the patient community.

Louise Rodino-Klapac, vice president of R&D and technical operations at Sarepta, emphasized the company's focus on completing regulatory interactions and submitting a biologics license application (BLA) for SRP-9003 as soon as possible, pending discussions with the FDA.

As Sarepta navigates these complex waters, the pharmaceutical industry watches closely to see if the company can overcome the regulatory challenges and bring a potentially transformative treatment to LGMD patients.