CAMBRIDGE, Mass., March 18, 2025 -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precisiongenetic medicine for rare diseases, shared the following safety update related to ELEVIDYS(delandistrogene moxeparvovec-rokl), the only approved gene therapy in patients with Duchennemuscular dystrophy.
We are profoundly saddened to share that a young man with Duchenne muscular dystrophy has passedaway following treatment with ELEVIDYS, having suffered acute liver failure. Acute liver injury is a knownpossible side effect of ELEVIDYS and other AAV-mediated gene therapies and is highlighted in theprescribing information. Although it is not a new safety signal and the benefit-risk of ELEVIDYS remainspositive, acute liver failure (ALF) leading to death represents a severity of acute liver injury notpreviously reported for ELEVIDYS, which to date has been used to treat more than 800 patients inclinical trials or as a prescribed therapy.
In addition, testing revealed this patient had a recent cytomegalovirus (CMV) infection which was identified by the treating physician as a possible contributing factor. CMV can infect and damage the liver, acondition known as CMV hepatitis.
Patient safety and well-being are Sarepta’s top priority. We continue to gather and analyze theinformation from this event. The event has been reported to the relevant health authorities and Sareptaintends to update the prescribing information to appropriately represent this event. We have alsoreported the event to ELEVIDYS clinical study investigators and prescribing physicians.
About ELEVIDYS (delandistrogene moxeparvovec-rokl)
ELEVIDYS (delandistrogene moxeparvovec-rokl) is a single-dose, adeno-associated virus (AAV)-basedgene transfer therapy for intravenous infusion designed to address the underlying genetic cause ofDuchenne muscular dystrophy – mutations or changes in the DMD gene that result in the lack ofdystrophin protein – through the delivery of a transgene that codes for the targeted production ofELEVIDYS micro-dystrophin in skeletal muscle.ELEVIDYS is indicated for the treatment of Duchenne muscular dystrophy (DMD) in individuals at least 4years 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 onexpression of ELEVIDYS micro-dystrophin (noted hereafter as “micro-dystrophin”) in skeletal muscle.Continued approval for this indication may be contingent upon verification and description of clinicalbenefit in a confirmatory trial(s).
IMPORTANT SAFETY INFORMATION
CONTRAINDICATION: ELEVIDYS is contraindicated in patients with any deletion in exon 8 and/or exon 9in the DMD gene.WARNINGS AND PRECAUTIONS:Infusion-related Reactions:
• Infusion-related reactions, including hypersensitivity reactions and anaphylaxis, have occurredduring or up to several hours following ELEVIDYS administration. Closely monitor patients duringadministration and for at least 3 hours after the end of infusion. If symptoms of infusion-relatedreactions occur, slow, or stop the infusion and give appropriate treatment. Once symptomsresolve, the infusion may be restarted at a lower rate.
• ELEVIDYS should be administered in a setting where treatment for infusion-related reactions isimmediately available.
• Discontinue infusion for anaphylaxis.
Acute Serious Liver Injury:
• Acute serious liver injury has been observed with ELEVIDYS, and administration may result inelevations of liver enzymes (such as GGT, GLDH, ALT, AST) or total bilirubin, typically seen within8 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. PostponeELEVIDYS administration in patients with acute liver disease until resolved or controlled.
• Prior to ELEVIDYS administration, perform liver enzyme test and monitor liver function (clinicalexam, 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 ELEVIDYSinfusion. Adjust corticosteroid regimen when indicated. If acute serious liver injury is suspected,consultation with a specialist is recommended.
Immune-mediated Myositis:
• In clinical trials, immune-mediated myositis has been observed approximately 1 month followingELEVIDYS infusion in patients with deletion mutations involving exon 8 and/or exon 9 in theDMD gene. Symptoms of severe muscle weakness, including dysphagia, dyspnea, andhypophonia, were observed.
• Limited data are available for ELEVIDYS treatment in patients with mutations in the DMD gene inexons 1 to 17 and/or exons 59 to 71. Patients with deletions in these regions may be at risk for asevere immune-mediated myositis reaction.
• Advise patients to contact a physician immediately if they experience any unexplained increasedmuscle pain, tenderness, or weakness, including dysphagia, dyspnea, or hypophonia, as thesemay be symptoms of myositis. Consider additional immunomodulatory treatment(immunosuppressants [e.g., calcineurin-inhibitor] in addition to corticosteroids) based onpatient’s clinical presentation and medical history if these symptoms occur.
Myocarditis:
• Acute serious myocarditis and troponin-I elevations have been observed following ELEVIDYSinfusion 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 beforeELEVIDYS infusion and weekly for the first month following infusion and continue monitoring ifclinically indicated. More frequent monitoring may be warranted in the presence of cardiacsymptoms, such as chest pain or shortness of breath.
• Advise patients to contact a physician immediately if they experience cardiac symptoms.
Preexisting Immunity against AAVrh74:
• In AAV-vector based gene therapies, preexisting anti-AAV antibodies may impede transgeneexpression at desired therapeutic levels. Following treatment with ELEVIDYS, all patientsdeveloped anti-AAVrh74 antibodies.
• Perform baseline testing for presence of anti-AAVrh74 total binding antibodies prior to ELEVIDYSadministration.
• ELEVIDYS administration is not recommended in patients with elevated anti-AAVrh74 totalbinding antibody titers greater than or equal to 1:400.
Adverse Reactions:
• The most common adverse reactions (incidence ≥5%) reported in clinical studies were vomiting,nausea, liver injury, pyrexia, and thrombocytopenia.Report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Sarepta Therapeutics at 1-888-SAREPTA (1-888-727-3782).
About Sarepta Therapeutics
Sarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastatelives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (Duchenne)and limb-girdle muscular dystrophies (LGMDs) and are building a robust portfolio of programs acrossmuscle, central nervous system, and cardiac diseases. For more information, please visitwww.sarepta.com or follow us on LinkedIn, X, Instagram and Facebook.
References:
1. U.S. Centers for Disease Control: https://www.cdc.gov/cytomegalovirus/about/index.html