Skip to main content
Lotties
1 - src: /sites/elevidyshcp/files/2024-09/ELE-HCP-1.1-Crecent-5-002.json / styles: top: -660px;left: -506px;width: 1134px;height: 1309px; / flip x: 0

A relentless, degenerative neuromuscular disease6

Dystrophin is a large protein found in muscle fibers throughout the body and plays a key structural role in maintaining the integrity of the sarcolemma during normal muscle contraction.3

With little or no dystrophin, people with Duchenne experience progressive and irreversible muscle wasting beginning at birth and continuing throughout life, with motor function worsening over time and leading to premature death.3,7,8

Muscle wasting
Consider options for intervention

Duchenne is a heterogeneous disease; every child progresses differently, and treatment experience will vary based on individual differences.9

Treatment intervention is critical for people with Duchenne regardless of age or magnitude.7 Even small amounts of endogenous dystrophin (<0.5%) have been shown to make a difference in critical functional parameters.10

 

 

Untreated patients experience a persistent loss of function

In the natural history of Duchenne, delays in motor development are present in early childhood. At younger ages, muscle growth and neurodevelopment mask decline, so during this time, observed increases or stabilization in motor function scores may conceal muscle degeneration.3,6

Boys with Duchenne typically demonstrate a peak NSAA score of 26 points around 6 years of age. From that point on, muscle loss has a more visible impact on daily function.12


Duchenne natural history: fitted mean trajectory
Duchenne natural history as measured by NSAA
  1. SKILL GAIN

    Muscle growth and neurodevelopment drive an increase in NSAA score at younger ages, masking muscle health decline in children with Duchenne6,12

  2. SKILL PLATEAU

    NSAA score generally peaks at a mean of 26 points at age 6.3 years. At this stage, the underlying disease process offsets skill gains made via muscle growth and neurodevelopment12,13

  3. SKILL DECLINE

    Increasing fibrosis and muscle loss lead to children with Duchenne losing ambulation between 10 and 13 years of age12,14,15

The NSAA scale is composed of 17 items and helps evaluate changes in gross motor ability over time. The aggregate score is based on the ability to perform a task or skill, such as rise from floor, ascend stairs, or walk, with scores of 0, 1, or 2 representing inability, ability with assistance, and complete independence, respectively.12

NSAA=North Star Ambulatory Assessment.

Timed function tests are early predictors of functional decline16

Untreated patients typically experience a decline on highly sensitive timed function tests (TFTs), which are often able to detect changes in motor function before aggregate measures.16-19

 

Duchenne natural history as measured by time function tests
Duchenne natural history as measured by time function tests

Both TTR and the 10MWR tests are strongly predictive of loss of ambulation, with key thresholds of >5 seconds and >10 seconds, respectively.20,21

MWR=meter walk/run; TTR=time to rise.

 

 

 

 

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
  • 6. Mendell JR, Khan N, Sha N, et al. Comparison of long-term ambulatory function in patients with Duchenne muscular dystrophy treated with eteplirsen and matched natural history controls. J Neuromuscul Dis. 2021;8(4):469-479. doi:10.3233/JND-200548
  • 7. 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
  • 8. 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.
  • 9. Fang Y, McDonald CM, Clemens PR, et al. Modeling early heterogeneous rates of progression in boys with Duchenne muscular dystrophy. J Neuromuscul Dis. 2023;10(3):349-364. doi:10.3233/JND-221527
  • 10. 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
  • 11. 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
  • 12. Muntoni F, Domingos J, Manzur AY, et al. Categorising trajectories and individual item changes of the North Star Ambulatory Assessment in patients with Duchenne muscular dystrophy. PLoS One. 2019;14(9):e0221097. doi:10.1371/journal.pone.0221097
  • 13. Mercuri E, Coratti G, Messina S, et al. Revised North Star Ambulatory Assessment for young boys with Duchenne muscular dystrophy. PLoS One. 2016;11(8):e0160195. doi:10.1371/journal.pone.0160195
  • 14. Emery AEH. The muscular dystrophies. Lancet. 2002;359(9307):687-695. doi:10.1016/S0140-6736(02)07815-7
  • 15. Niks EH, Aartsma-Rus A. Exon skipping: a first in class strategy for Duchenne muscular dystrophy. Expert Opin Biol Ther. 2017;17(2):225-236. doi:10.1080/14712598.2017.1271872
  • 16. Arora H, Willcocks RJ, Lott DJ, et al. Longitudinal timed function tests in Duchenne muscular dystrophy: Imaging DMD cohort natural history. Muscle Nerve. 2018;58(5):631-638. doi:10.1002/mus.26161
  • 17. Verhulst B, Neale MC. Best practices for binary and ordinal data analyses. Behav Genet. 2021;51(3):204-214. doi:10.1007/s10519-020-10031-x
  • 18. Stimpson G, Ridout D, Wolfe A, et al. Quantifying variability in motor function in Duchenne muscular dystrophy: UK centiles for the North Star Ambulatory Assessment, 10 m walk run velocity and rise from floor velocity in GC treated boys. J Neuromuscul Dis. 2024;11(1):153-166. doi:10.3233/JND-230159
  • 19. Mazzone ES, Messina S, Vasco G, et al. Reliability of the North Star Ambulatory Assessment in a multicentric setting. Neuromuscul Disord. 2009;19(7):458-461. doi:10.1016/j.nmd.2009.06.368
  • 20. Zambon AA, Gupta VA, Ridout D, et al. Peak functional ability and age at loss of ambulation in Duchenne muscular dystrophy. Dev Med Child Neurol. 2022;64(8):979-988. doi:10.1111/dmcn.15176
  • 21. Muntoni F, Signorovitch J, Sajeev G, et al. DMD genotypes and motor function in Duchenne muscular dystrophy: a multi-institution meta-analysis with implications for clinical trials. Neurology. 2023;100(15):e1540-e1554. doi:10.1212/WNL.0000000000201626

Indication

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 (noted hereafter as “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).

 

Important Safety Information

CONTRAINDICATION:
ELEVIDYS is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the DMD gene.

WARNINGS AND PRECAUTIONS:
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 administration 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. 

Acute Serious Liver Injury:

  • 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 (eg, 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.

Immune-mediated Myositis:

  • 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 [eg, calcineurin-inhibitor] in addition to corticosteroids) based on patient’s clinical presentation and medical history if these symptoms occur.

Myocarditis:

  • 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.

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 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.

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).

Please see full Prescribing Information.

Read More Close