WHA

Skysona (elivaldogene autotemcel suspension)

Medical Administration – intravenous

Diagnosis considered for coverage:
  • Indicated to slow the progression of neurologic dysfunction in boys 4-17 years of age with early, active cerebral adrenoleukodystrophy (CALD). Early, active cerebral adrenoleukodystrophy refers to asymptomatic or mildly symptomatic (neurologic function score, NFS ≤ 1) boys who have gadolinium enhancement on brain magnetic resonance imaging (MRI) and Loes scores of 0.5-9. This indication is approved under accelerated approval based on 24-month Major Functional Disability (MFD)-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
  • Limitations of Use:
    • Skysona does not prevent the development of or treat adrenal insufficiency due to adrenoleukodystrophy.
    • An immune response to Skysona may limit the persistence of descendent cells of Skysona, causing rapid loss of efficacy of Skysona in patients with full deletions of the human adenosine triphosphate binding cassette, sub family D, member 1 (ABCD1) transgene.
    • Skysona has not been studied in patients with CALD secondary to head trauma.
    • Given the risk of hematologic malignancy with Skysona, and unclear long-term durability of Skysona and human adrenoleukodystrophy protein (ALDP) expression, careful consideration should be given to the appropriateness and timing of treatment for each boy, especially for boys with isolated pyramidal tract disease based on available treatment options since their clinical symptoms do not usually occur until adulthood.
       
Coverage Criteria:

For diagnosis of active cerebral adrenoleukodystrophy (CALD):

  • Dose does not exceed 1 single dose for infusion containing a suspension of CD34+ cells in one or two infusion bags (5.0 x 106 CD34+ cells/kg), AND
  • Prescribed by a stem cell transplant physician from a qualified treatment center, AND
  • BOTH of the following:
    • Patient is male sex 
    • Patient is 4 to 17 years of age, AND
  • Diagnosis of early, active cerebral adrenoleukodystrophy (CALD), AND
  • Molecular genetic testing confirms mutation in the ABCD1 gene, AND
  • ALL of the following:
    • Patient has elevated very long chain fatty acid (VLCFA) levels 
    • Loes score between 0.5 and 9 (inclusive) based on brain MRI assessment 
    • Brain magnetic resonance imaging (MRI) utilizes Gadolinium enhancement (GdE +) and demonstrates demyelinating lesions
    • Neurologic function score (NFS) less than or equal to 1, AND
  • Patient is not eligible for an allogeneic hematopoietic stem cell transplant with an HLA-matched sibling donor, AND
  • Patient has obtained a negative test result for all of the following prior to cell collection:
    • Hepatitis B virus (HBV) 
    • Hepatitis C virus (HCV) 
    • Human T-lymphotropic virus 1 and 2 (HTLV-1/HTLV-2) 
    • Human immunodeficiency virus (HIV), AND
  • Patient does not have CALD secondary to head trauma, AND
  • Discontinue prophylactic anti-retroviral medications (e.g., Truvada, Descovy) for at least one month prior to initiating medications for stem cell mobilization and until all cycles of apheresis are completed, AND
  • Patient has never received Skysona treatment in their lifetime
Coverage Duration: 
  • 1 time authorization in lifetime
Authorization is not covered for the following:


The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.
 

Additional Information: 
  • Skysona is for autologous use only.
  • Skysona is a cell suspension for intravenous infusion.
  • Skysona is composed of one or two infusion bags which contain 4 to 30 × 106 cells/mL suspended in cryopreservation solution. Each infusion bag contains approximately 20 mL of Skysona. A single dose of Skysona contains a minimum of 5.0 × 106 CD34+ cells per kg of body weight, suspended in cryopreservation solution.
  • Before mobilization, apheresis, and conditioning are initiated, confirm that hematopoietic stem cell (HSC) transplantation is appropriate for the patient.
  • Perform screening for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus 1 & 2 (HIV-1/HIV-2) and Human T-lymphotropic virus 1 & 2 (HTLV-1/HTLV-2) in accordance with clinical guidelines before collection of cells for manufacturing.
  • Warnings/Precautions include:
    • Hematologic Malignancy
    • Serious Infections
    • Prolonged Cytopenias
    • Delayed Platelet Engraftment
    • Risk of Neutrophil Engraftment Failure
    • Hypersensitivity Reactions
    • Anti-retroviral Use
    • Laboratory Test Interference
  • The safety and effectiveness of vaccination during or following Skysona treatment have not been studied. Vaccination is not recommended during the 6 weeks preceding the start of myeloablative conditioning, and until hematological recovery following treatment with Skysona. Where feasible, administer childhood vaccinations prior to myeloablative conditioning for Skysona.
  • Loes is a 34-point imaging-based scoring system for patients with X-Linked Adrenoleukodystrophy to assess neuroanatomical involvement and the presence or absence of focal or global atrophy. The score helps in the prediction of disease course and selection of patients for HSCT.
  • Gadolinium is a contrast-agent used to enhance MRI imaging of the CNS
  • Skysona has not been studied in CALD secondary to head trauma.
Policy Updates:
  • 2/21/2023 – New policy approved by P&T.
References:


1.    Skysona Prescribing Information. Bluebird Bio, Inc. Somerville, MA. September 2022. 
2.    Eichler, F., Duncan, C., et al. Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy. N Engl J Med 2017; 377:1630-1638. Available at DOI: 10.1056/NEJMoa1700554. Accessed October 13, 2022. 
3.    Rare Disease Database. X-Linked Adrenoleukodystrophy. Available at https://rarediseases.org/rare-diseases/adrenoleukodystrophy/. Accesed October 13,2022. 
4.    Kumar, S., Sait. H., et al. Loes Score: Clinical and Radiological Profile of 22 Patients of X-Linked Adrenoleukodystrophy: Case Series from a Single Center. Indian J Radiol Imaging 2021;31:383–390. Available at https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0041-1734366.pdf. Accessed October 18, 2022. 
5.    Ibrahim, M., Hazhirkarzar, B., et al. Gadolinium Magnetic Resonance Imaging. Available at https://www.ncbi.nlm.nih.gov/books/NBK482487/. Accessed October 18, 2022. 
6.    Bluebird bio Receives FDA Accelerated Approval for SKYSONA® Gene Therapy for Early, Active Cerebral Adrenoleukodystrophy (CALD). Available at https://investor.bluebirdbio.com/news-releases/news-release-details/bluebird-bio-receives-fda-accelerated-approval-skysonar-gene. Accessed October 18, 2022. 

Last review date: March 1, 2023