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Dystrophin is vital for muscle function3

Duchenne muscular dystrophy is caused by a mutation in the DMD gene that prevents the body from producing dystrophin, a large protein found in muscle fibers throughout the body that is essential for muscle membrane stability.3

It’s critical to consider early intervention before essential functions are irreversibly lost9

Dystrophin plays a critical structural role in maintaining the integrity of the sarcolemma during normal muscle contraction.3

Dystrophin plays a critical role in normal muscle function

With little or no dystrophin, muscles suffer progressive and irreversible damage beginning at birth. As muscle fibers experience repeated contraction-induced injuries over time, they are replaced with fat or fibrous connective tissue, with limited potential for recovery.8,10

Without dystrophin, muscles suffer progressive and irreversible damage

Without intervention, motor function worsens, and premature death occurs, typically in the second or third decade of life.3,11

Preservation of function is an important goal for all people with Duchenne, regardless of age or severity, as even amounts of endogenous dystrophin (<0.5%) have been shown to make a difference in critical functional parameters10,12

References:

  • 3. Asher DR, Thapa K, Dharia SD, et al. Clinical development on the frontier: gene therapy for Duchenne muscular dystrophy. Expert Opin Biol Ther. 2020;20(3):263-274. doi:10.1080/14712598.2020.1725469
  • 8. Mendell JR, Sahenk Z, Lehman K, et al. Assessment of systemic delivery of rAAVrh74.MHCK7.micro-dystrophin in children with Duchenne muscular dystrophy: a nonrandomized controlled trial. JAMA Neurol. 2020;77(9):1122-1131. doi:10.1001/jamaneurol.2020.1484
  • 9. Mercuri E, Pane M, Cicala G, Brogna C, Ciafaloni E. Detecting early signs in Duchenne muscular dystrophy: comprehensive review and diagnostic implications. Front Pediatr. 2023;11:1276144. doi:10.3389/fped.2023.1276144
  • 10. Mendell JR, Proud C, Zaidman CM, et al. Practical considerations for delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy. Pediatr Neurol. 2024;153:11-18. doi:10.1016/j.pediatrneurol.2024.01.003
  • 11. Magliano L, D’Angelo MG, Vita G, et al. Psychological and practical difficulties among parents and healthy siblings of children with Duchenne vs. Becker muscular dystrophy: an Italian comparative study. Acta Myol. 2014;33(3):136-143.
  • 12. de Feraudy Y, Ben Yaou R, Wahbi K, et al. Very low residual dystrophin quantity is associated with milder dystrophinopathy. Ann Neurol. 2021;89(2):280-292. doi:10.1002/ana.25951

Indication

ELEVIDYS is indicated for the treatment of ambulatory patients 4 years of age and older with Duchenne muscular dystrophy (DMD) who have a confirmed mutation in the DMD gene.

Limitations of Use
ELEVIDYS is not recommended in patients with:

  • Preexisting liver impairment (defined as gamma-glutamyl transferase [GGT] > 2 x upper limit of normal or total bilirubin > the upper limit of normal not due to Gilbert's syndrome) or active hepatic viral infection due to the high risk of acute serious liver injury and acute liver failure.
  • Recent vaccination (within 4 weeks of treatment) due to immunogenicity and potential safety concerns.
  • Active or recent (within 4 weeks) infections due to safety concerns.

Please see full Prescribing Information, including Boxed Warning, and Medication Guide.

Important Safety Information, including Boxed Warning

BOXED WARNING: Acute Serious Liver Injury and Acute Liver Failure

Acute serious liver injury, including life-threatening and fatal acute liver failure, has occurred.
Patients with preexisting liver impairment may be at higher risk. 

Prior to infusion, assess liver function by clinical examination and laboratory testing. Administer systemic corticosteroids before and after ELEVIDYS infusion. Continue to monitor liver function weekly for the first 3 months after infusion and continue until results are unremarkable. 

Instruct patients to maintain proximity to an appropriate healthcare facility, as determined by the healthcare provider, for at least 2 months following ELEVIDYS infusion.

Obtain prompt consultation with a specialist (e.g., gastroenterologist or hepatologist) if acute serious liver injury or impending acute liver failure is suspected.

CONTRAINDICATION
ELEVIDYS is contraindicated in patients with any deletion in exon 8 and/or exon 9, including a deletion of any portion or the entirety of these exons, in the DMD gene. 

WARNINGS AND PRECAUTIONS
Acute Serious Liver Injury and Acute Liver Failure
See Boxed Warning.

  • Acute serious liver injury marked by elevations of liver enzymes (e.g., GGT, ALT) and total bilirubin and acute liver failure has occurred with ELEVIDYS. Onset of the liver injury typically begins within 8 weeks of ELEVIDYS administration. In non-ambulatory patients treated with ELEVIDYS, acute liver failure with fatal outcome has occurred in the clinical and post-marketing settings.
  • Life-threatening mesenteric vein thrombosis, complicated by bowel ischemia and necrosis, and portal hypertension have been reported following acute liver injury associated with ELEVIDYS in a non-ambulatory patient.
  • 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 or acute liver failure. Postpone ELEVIDYS administration in patients with acute liver disease until resolved or controlled.
  • Systemic corticosteroid treatment is recommended for patients before and after ELEVIDYS infusion. Adjust corticosteroid regimen when indicated.

Serious infections

  • Increased susceptibility to serious infections may occur due to concomitant administration of corticosteroid regimen and additional immunosuppressants, and ELEVIDYS. Serious respiratory infections, including with fatal outcomes, have occurred in patients taking immunosuppressant corticosteroids required for ELEVIDYS administration.
  • Monitor patients for signs and symptoms of infection before and after ELEVIDYS administration and treat appropriately.
  • Administer immunizations according to best clinical practices and immunization guidelines prior to initiation of the corticosteroid regimen required before ELEVIDYS infusion.
  • Avoid administration of ELEVIDYS to patients with active infections.

Myocarditis

  • Acute, serious, life-threatening myocarditis and troponin-I elevations have been observed within 24 hours to more than 1 year following ELEVIDYS infusion.
  • 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, until results return to near baseline levels or stabilize.
  • 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.

Infusion-related Reactions

  • Infusion-related reactions, including hypersensitivity reactions and anaphylaxis, have occurred during or up to several hours following ELEVIDYS administration. Closely monitor patients during and for at least 3 hours after the end of infusion. If symptoms of infusion-related reactions occur, slow or stop the infusion and give appropriate treatment. Once symptoms resolve, the infusion may be restarted at a lower rate.
  • ELEVIDYS should be administered in a setting where treatment for infusion-related reactions is immediately available.
  • Discontinue infusion for anaphylaxis. 

Immune-mediated Myositis

  • Immune-mediated myositis, including serious and life-threatening events, has occurred approximately 1 month following ELEVIDYS infusion. Signs and symptoms include severe muscle weakness, including dysphagia, dyspnea, dysphonia, and hypophonia.
  • Severe to life-threatening immune-mediated myositis has been reported in patients with deletions including portions of exons 1-17 and/or exons 59-71 of the DMD gene.
  • Regardless of genetic mutation, advise patients to contact a physician immediately if they experience any unexplained increased muscle pain, tenderness, or weakness, including dysphagia, dyspnea, dysphonia, or hypophonia, as these may be symptoms of myositis. Consider additional immunomodulatory treatment based on patient's clinical presentation and medical history if these symptoms occur.

Preexisting Immunity against AAVrh74

  • 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 the 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 ≥1:400.

ADVERSE REACTIONS

  • The most common adverse reactions (incidence ≥5%) reported in clinical studies were vomiting, nausea, liver injury, pyrexia, thrombocytopenia, and troponin-I increased.

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).

Please see full Prescribing Information, including Boxed Warning, and Medication Guide.