Last Review Date: 04/07/2025

Date of Origin: 04/04/2024

Dates Reviewed: 04/2024, 04/2025

1. Length of Authorization

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

2. Dosing Limits

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

• A single dose of Lenmeldy contains 2 to 11.8× 10⁶ cells/mL (1.8 to 11.8 x 10⁶ CD34+ cells/mL) suspended in one to eight patient-specific infusion bags

3. Initial Approval Criteria ¹

Coverage is provided for the following conditions:

• Patient is less than 18 years of age; AND
• Patient is screened and found to be negative for hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotropic virus 1 & 2 (HTLV-1/HTLV-2), human immunodeficiency virus 1 & 2 (HIV-1/HIV-2), and mycoplasma infection before collection of cells for manufacturing; AND
• Patient will not be administered vaccinations during the 6 weeks preceding the start of myeloablative conditioning, and until hematological recovery following treatment (Note: Where feasible, administer childhood vaccinations prior to myeloablative conditioning); AND
• Patient risk factors for thrombosis as well as veno-occlusive disease have been evaluated prior to administration; AND
• Prophylaxis for infection will be followed according to standard institutional guidelines; AND
• Patient will be monitored for hematological malignancies periodically after treatment; AND
• Patients will not receive prophylactic HIV anti-retroviral therapy for at least one-month preceding mobilization (Note: anti-retrovirals may interfere with manufacturing); AND
• Patient will have mobilization of stem cells using granulocyte-colony stimulating factor (G-CSF with or without plerixafor); AND
• Used as single agent therapy (Note: not inclusive of busulfan conditioning regimen); AND
• Patient has not received a prior allogeneic stem cell transplant (or has, but is without evidence of residual donor cells present), and is a candidate for autologous stem cell transplantation (e.g., adequate renal and hepatic function); AND
• Patient does not have a known and available suitable 10/10 human leukocyte antigen matched related donor willing to participate in an allogeneic HSCT; AND
• Patient has not received other gene therapy for MLD; AND

Metachromatic Leukodystrophy (MLD) † Ф

• Patient has a confirmed diagnosis of MLD (also known as arylsulfatase A deficiency) as evidenced by the following biochemical and molecular markers:
  • Arylsulfatase A (ARSA) enzyme activity below the normal range in peripheral blood leukocytes or fibroblasts OR increased urinary excretion of sulfatides; AND
  • Presence of biallelic ARSA pathogenic mutation of known or novel polymorphisms (Note: For patients with novel mutation(s), a 24-hour urine collection must show elevated sulfatide levels); AND
• Patient has pre-symptomatic late infantile (PSLI), presymptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ) disease (Note: Requests for children with late juvenile form of the disease will be reviewed on a case-by-case basis)

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

4. Renewal Criteria

• Duration of authorization has not been exceeded (refer to Section I)

5. Dosage/Administration

6. Billing Code/Availability Information

HCPCS Code:

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

NDC(s):

• Lenmeldy containing 2 to 11.8× 10⁶ cells/mL (1.8 to 11.8 x 10⁶ CD34+ cells/ml) suspended in one to eight patient-specific infusion bags: 83222-0200-xx

7. References

1. Lenmeldy [package insert]. Boston, MA; Orchard Therapeutics NA; March 2024. Accessed February 2025.

2. ClinicalTrials.gov. An Open Label, Non-randomized Trial to Evaluate the Safety and Efficacy of a Single Infusion of OTL-200 in Patients With Late Juvenile (LJ) Metachromatic Leukodystrophy (MLD). https://clinicaltrials.gov/study/NCT04283227?intr=Atidarsagene&rank=1.
3. Biffi A, Montini E, Lorioli L, et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science. 2013;341(6148):1233158. doi:10.1126/science.1233158
4. Fumagalli F, Calbi V, Natali Sora MG, et al. Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access. Lancet. 2022;399(10322):372-383. doi:10.1016/S0140-6736(21)02017-1
5. Sessa M, Lorioli L, Fumagalli F, et al. Lentiviral haemopoietic stem-cell gene therapy in early-onset metachromatic leukodystrophy: an ad-hoc analysis of a non-randomised, open-label, phase 1/2 trial. Lancet. 2016;388(10043):476-487. doi:10.1016/S0140-6736(16)30374-9
6. ClinicalTrials.gov. A Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Treatment of Metachromatic Leukodystrophy. https://clinicaltrials.gov/study/NCT01560182?intr=NCT01560182&rank=1.
7. Gomez-Ospina N. Arylsulfatase A Deficiency. 2006 May 30 [Updated 2024 Apr 25]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1130/. Accessed February 2025.
8. Wang RY, Bodamer OA, Watson MS, et al. Lysosomal storage diseases: Diagnostic confirmation and management of presymptomatic individuals. ACMG Standards and Guidelines. Genet Med. 2011;13:457-84.
9. Schoenmakers DH, Mochel F, Adang LA, et al. Inventory of current practices regarding hematopoietic stem cell transplantation in metachromatic leukodystrophy in Europe and neighboring countries. Orphanet J Rare Dis 2024; 19:46.
10. Bonkowsky JL. Metachromatic leukodystrophy. In: Firth HV, Dashe JF (Eds.). UpToDate. Last updated July 11, 2024. Available at: https://www.uptodate.com/contents/metachromatic-leukodystrophy. Accessed March 2025.
11. Page KM, Stenger, EO, Connelly JA, et al. Hematopoietic Stem Cell Transplantation to Treat Leukodystrophies: Clinical Practice Guidelines from the Hunter’s Hope Leukodystrophy Care Network. Biol Blood Marrow Transplant. 2019 Dec;25(12):e363-e374.

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