Last Review Date: 02/01/2024

Date of Origin: 10/03/2022

Dates Reviewed: 10/2022, 02/2023, 02/2024

1. Length of Authorization ¹

Coverage will be provided for one treatment course (1 dose of Skysona) and may NOT be renewed.

2. Dosing Limits

A. Quantity Limit (max daily dose) [NDC Unit]:

• A single dose of Skysona containing a minimum of 5.0 x 10⁶ CD34+ cells/kg of body weight, in one or more infusion bags.

B. Max Units (per dose and over time) [HCPCS Unit]:

• A single dose of Skysona containing a minimum of 5.0 x 10⁶ CD34+ cells/kg of body weight, in one or more infusion bags

3. Initial Approval Criteria ¹

     Coverage is provided in the following conditions:

• Patient is a male at least 4 years of age and less than 18 years of age; AND
• Patient has been screened for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus 1 & 2 (HIV-1/HIV-2), and human T-lymphotrophic virus 1 & 2 (HTLV-1/HTLV-2) in accordance with clinical guidelines prior to collection of cells for manufacturing; AND
• Patient does not have an active infection, including clinically important localized infections; AND
• Patient will be administered prophylaxis for infection according to best clinical practices and guidelines; AND
• Vaccinations will not be administered within the 6 weeks prior to the start of therapy and will not be administered concurrently while on therapy AND patient is up to date with all age-appropriate vaccinations, in accordance with current vaccination guidelines, prior to initiating therapy; AND
• Used as single agent therapy (not applicable to lymphodepleting or bridging therapy while awaiting manufacture); AND
• Patient will receive periodic life-long monitoring for hematological malignancies (e.g., myelodysplastic syndrome [MDS]); AND
• Patient does not have a full ABCD1 gene deletion; AND
• Patient will avoid concomitant therapy with anti-retroviral medications for at least one month prior to initiating medications for stem cell mobilization and for the expected duration for elimination of the medications, and until all cycles of apheresis are completed (Note: if a patient requires anti-retroviral for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization); AND
• Patient does not have disease secondary to head trauma; AND
• Therapy will not be used to prevent the development of or treat adrenal insufficiency due to adrenoleukodystrophy; AND
• Patient is eligible§ to undergo hematopoietic stem cell transplant (HSCT) and has not had a prior allogeneic-HSCT; AND
• Males capable of fathering a child and their female partners of childbearing potential should use an effective method of contraception (e.g., intra-uterine device or combination of hormonal and barrier contraception) from start of mobilization through at least 6 months after administration of Skysona; AND

Cerebral Adrenoleukodystrophy (CALD) † Ф ^1-6

• Patient has a documented diagnosis of cerebral adrenoleukodystrophy (CALD)* as defined by one or more of the following:
  • Elevated very long chain fatty acids (VLCFA) as confirmed by the following:
    • Plasma C26:0-lysophosphatidylcholine (C26:0-LPC) level; OR
    • Fasting plasma VLCFA levels: C26:0, ratio of C24:0 to C22:0, AND ratio of C26:0 to C22:0; OR
  • Pathogenic variants in the ABCD1 gene as detected by genetic testing; AND
• Patient has active central nervous system (CNS) disease established by central radiographic review of brain magnetic resonance imaging (MRI) demonstrating both of the following:
  • Loes score between 0.5 and 9 (inclusive) on the 34-point scale; AND
  • Gadolinium enhancement on MRI of demyelinating lesions; AND
• Neurologic Function Score (NFS) ≤ 1 (asymptomatic or mildly symptomatic disease)

*Note: Patients with isolated pyramidal tract disease will be reviewed on a case-by-case basis

§ Eligibility criteria for allogeneic HCT are not absolute and vary by center. In general, patients are considered eligible for allogeneic HCT if they meet certain criteria like functional capacity, organ function, social support, etc.

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

Coverage may NOT be renewed.

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code(s):

• J3590 – Unclassified biologics
• C9399 – Unclassified drugs or biologicals (hospital outpatient use ONLY)

NDC:

• Skysona up to 2 infusion bags, 20 mL/infusion bag, overwrap, and metal cassette: 73554-2111-xx

7. References

1. Skysona [package insert]. Somerville, MA; Bluebird bio, Inc.; September 2022. Accessed January 2024.
2. Raymond GV, Moser AB, Fatemi A. X-Linked Adrenoleukodystrophy. Initial Posting: March 26, 1999; Last Update: April 6, 2023. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1315/. Accessed January 2024.
3. Eichler F, Duncan C, Musolino PL, et al. Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy. N Engl J Med. 2017 Oct 26;377(17):1630-1638. doi: 10.1056/NEJMoa1700554. Epub 2017 Oct 4.
4. Moser HW, Loes DJ, Melhem ER, et al (2000) X-Linked adrenoleukodystrophy: overview and prognosis as a function of age and brain magnetic resonance imaging abnormality. A study involving 372 patients. Neuropediatrics 31:227–39. doi: 10.1055/s-2000-9236
5. Moser HW, Loes DJ, Melhem ER, et al. A Phase 2/3 Study of the Efficacy and Safety of Hematopoietic Stem Cells Transduced With Lenti-D Lentiviral Vector for the Treatment of Cerebral Adrenoleukodystrophy (CALD) – Clinical Trial Protocol. EudraCT No. 2011-001953-10. Registry name identifier: NCT01896102. Available at:  https://clinicaltrials.gov/ProvidedDocs/02/NCT01896102/Prot_000.pdf
6. Engelen M, van Ballegoij WJC, Mallack EJ, et al. International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy: A Consensus-Based Approach. Neurology 2022; 99:940.

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan..

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD/LCA): N/A