Sarepta Therapeutics, Inc. Shares New Protein Expression and Safety Results from Endeavor in Participants 2 Years Old At Time of Treatment

Published: 2025-05-16 12:36:28 ET SRPT

Published on 05/16/2025 at 12:36

Sarepta Therapeutics, Inc. reported new results from Study 9001-103. Also known as ENDEAVOR, Study 9001-103 is a multi-cohort study of ELEVIDYS (delandistrogene moxeparvovec-rokl) for the treatment of Duchenne muscular dystrophy. Treatment with ELEVIDYS in the ENDEAVOR participants in cohort 6 who were 2 years old at the time of treatment (n=6), demonstrated mean expression of 93.87% of normal, as measured by western blot, and 79.9% dystrophin positive fibers (PDPF), as measured by immunofluorescence.

The results were seen in biopsies taken 12 weeks after treatment. Safety in cohort 6 was consistent with clinical and real-world experience with ELEVIDYS. The most common adverse events were nausea and vomiting.

Elevated liver enzymes were seen in two patients and resolved with steroid administration. The primary endpoint in ENDEAVOR is the change from baseline in the quantity of ELEVIDYS micro-dystrophin protein expression measured by western blot at 12 weeks. Secondary outcome measures include change from baseline in micro-dystrophin expression measured by percent dystrophin positive fibers at 12 weeks.

Exploratory endpoints include the change in vector genome copies per nucleus, NSAA and certain timed functional tests. Including the initial 12-week period, patients are followed for a total of five years. ELEVIDYS (delandistrogene moxeparvovec-rokl) is a single-dose, adeno-associated virus (AAV)-based gene transfer therapy for intravenous infusion designed to address the underlying genetic cause of Duchenne muscular dystrophy ?

mutations or changes in the DMD gene that result in the lack of dystrophin protein ? through the delivery of a transgene that codes for the targeted production of ELEVIDYS micro-dystrophin in skeletal muscle. ELEVIDYS is indicated for the treatment of Duchenne muscular dystrophy (DMD) in individuals at least 4 years of age.

For patients who are ambulatory and have a confirmed mutation in the DMD gene For patients who are non-ambulatory and have a confirmed mutation in the DMD gene. The DMD indication in non-ambulatory patients is approved under accelerated approval based on expression of ELEVIDYS micro-dystrophin in skeletal muscle. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Acute serious liver injury has been observed with ELEVIDYS, and administration may result in elevations of liver enzymes (such as GGT, GLDH, ALT, AST) or total bilirubin, typically seen within 8 weeks. Patients with preexisting liver impairment, chronic hepatic condition, or acute liver disease (e.g., acute hepatic viral infection) may be at higher risk of acute serious liver injury. Postpone ELEVIDYS administration in patients with acute liver disease until resolved or controlled.

Prior to ELEVIDYS administration, perform liver enzyme test and monitor liver function (clinical exam, GGT, and total bilirubin) weekly for the first 3 months following ELEVIDYS infusion. Continue monitoring if clinically indicated, until results are unremarkable (normal clinical exam, GGT, and total bilirubin levels return to near baseline levels). Systemic corticosteroid treatment is recommended for patients before and after ELEVIDYS infusion.

Adjust corticosteroid regimen when indicated. If acute serious liver injury is suspected, consultation with a specialist is recommended. In clinical trials, immune-mediated myositis has been observed approximately 1 month following ELEVIDYS infusion in patients with deletion mutations involving exon 8 and/or exon 9 in the DMD gene.

Symptoms of severe muscle weakness, including dysphagia, dyspnea, and hypophonia, were observed. Limited data are available for ELEVIDYS treatment in patients with mutations in the DMD gene in exons 1 to 17 and/or exons 59 to 71. Patients with deletions in these regions may be at risk for a severe immune-mediated myositis reaction.

Advise patients to contact a physician immediately if they experience any unexplained increased muscle pain, tenderness, or weakness, including dysphagia, dyspnea, or hypophonia, as these may be symptoms of myositis. Consider additional immunomodulatory treatment (immunosuppressants [e.g., calcineurin-inhibitor] in addition to corticosteroids) based on patient?s clinical presentation and medical history if these symptoms occur. Acute serious myocarditis and troponin-I elevations have been observed following ELEVIDYS infusion in clinical trials.

If a patient experiences myocarditis, those with pre-existing left ventricle ejection fraction (LVEF) impairment may be at higher risk of adverse outcomes. Monitor troponin-I before ELEVIDYS infusion and weekly for the first month following infusion and continue monitoring if clinically indicated. More frequent monitoring may be warranted in the presence of cardiac symptoms, such as chest pain or shortness of breath.

Advise patients to contact a physician immediately if they experience cardiac symptoms. In AAV-vector based gene therapies, preexisting anti-AAV antibodies may impede transgene expression at desired therapeutic levels. Following treatment with ELEVIDYS, all patients developed anti-AAVrh74 antibodies. Perform baseline testing for presence of anti-AAVrh74 total binding antibodies prior to ELEVIDYS administration.

ELEVIDYS administration is not recommended in patients with elevated anti-AAVrh74 total binding antibody titers greater than or equal to 1:400.