Last Review Date: 01/04/2024

Date of Origin: 01/04/2024

Dates Reviewed: 01/2024

1. Length of Authorization

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

2. Dosing Limits

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

• A single dose of Lyfgenia containing a minimum of 3.0 × 10⁶ CD34+ cells/kg of body weight, in one or more infusion bags

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

• A single dose of Lyfgenia containing a minimum of 3.0 × 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 at least 12 years of age; AND
• Provider has considered use of prophylaxis therapy for seizures prior to initiating myeloablative conditioning; AND
• Patient will be monitored for hematologic malignancies periodically after treatment; AND
• Must not be administered concurrently with live vaccines while immunosuppressed; AND
• Patient does not have a history of hypersensitivity to dimethyl sulfoxide (DMSO) or dextran 40; AND
• Patient is HIV negative as confirmed by a negative HIV test prior to mobilization (Note: Patients who have received Lyfgenia are likely to test positive by polymerase chain reaction (PCR) assays for HIV due to integrated BB305 LVV proviral DNA, resulting in a possible false-positive PCR assay test result for HIV. Therefore, patients who have received Lyfgenia should not be screened for HIV infection using a PCR-based assay.); AND
• Patient will not receive therapy concomitantly with any of the following:
  • Hydroxyurea for at least 2 months prior to mobilization and until all cycles of apheresis are completed (Note: If hydroxyurea is administered between mobilization and conditioning, discontinue 2 days prior to initiation of conditioning); AND
  • Myelosuppressive iron chelators (e.g., deferiprone, etc.) for 7-days prior to mobilization, conditioning, and 6 months post-treatment; AND
  • Disease-modifying agents (e.g., L-glutamine, vexelotor, crizanlizumab) for at least 2 months prior to mobilization; AND
  • Prophylactic HIV anti-retroviral therapy (Note: Patients receiving prophylactic ART should stop therapy for at least one month prior to mobilization and until all cycles of apheresis are completed); AND
  • Mobilization of stem cells using granulocyte-colony stimulating factor (G-CSF); AND
  • Erythropoietin for at least 2 months prior to mobilization; AND
• Patient has not received other gene therapy [e.g., Casgevy™ (exagamglogene autotemcel)] *; AND
• Patient is a candidate for autologous hematopoietic stem cell transplant (HSCT); AND
• Patient does not have a known 10/10 human leukocyte antigen matched related donor willing to participate in an allogeneic HSCT; AND
• Patient will be transfused at least twice (once each month) prior to mobilization to reach a target Hb of 8-10 g/dL (less than 12 g/dL) and <30% HbS; AND

Sickle Cell Disease ^1-3 † Ф

• Patient has a confirmed diagnosis of sickle-cell disease (includes genotypes βS/βS or βS/β0 or βS/β+) as determined by one of the following:
  • Identification of significant quantities of HbS with or without an additional abnormal β-globin chain variant by hemoglobin assay; OR
  • Identification of biallelic HBB pathogenic variants where at least one allele is the p.Glu6Val pathogenic variant on molecular genetic testing; AND
• Patient does NOT have disease with more than two α-globin gene deletions; AND
• Patient has symptomatic disease despite treatment with hydroxyurea and add-on therapy (e.g.,  crizanlizumab, voxelotor, etc.); AND
• Patient experienced two or more vaso-occlusive events/crises (VOE/VOC)* in the previous year while adhering to the above therapy

*VOE/VOC is defined as an event requiring a visit to a medical facility for evaluation which results in a diagnosis of such being documented due to one (or more) of the following: acute pain, acute chest syndrome, acute splenic sequestration, acute hepatic sequestration, priapism lasting > 2 hours AND necessitating subsequent interventions such as opioid pain management, non-steroidal anti-inflammatory drugs, RBC transfusion, etc.

*Requests for subsequent use of lovotibeglogene after receipt of exagamglogene autotemcel will be evaluated on a case-by-case basis

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

4. Renewal Criteria ^1,3

• Coverage cannot be renewed.

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS:

• J3590 – Unclassified biologics

NDC:

• Lyfgenia is supplied in one to four infusion bags containing a frozen suspension of genetically modified autologous cells, enriched for CD34+ cells, 20 mL infusion bag, overwrap, and metal cassette: 73554- 1111-xx

7. References

1. Lyfgenia [package insert]. Somerville, MA; Bluebird Bio, Inc., December 2023. Accessed December 2023.
2. Kanter J, Thompson AA, Pierciey FJ Jr, et al. Lovo-cel gene therapy for sickle cell disease: Treatment process evolution and outcomes in the initial groups of the HGB-206 study. Am J Hematol. 2023 Jan;98(1):11-22. doi: 10.1002/ajh.26741. Epub 2022 Oct 10. PMID: 36161320; PMCID: PMC10092845.
3. Bender MA, Carlberg K. Sickle Cell Disease. 2003 Sep 15 [Updated 2022 Nov 17]. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1377/.
4. Yawn BP, Buchanan GR, Afenyi-Annan AN, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014 Sep 10;312(10):1033-48.
5. Tisdale JF, Pierciey FJ, Bonner M, et al. (2020) Safety and feasibility of hematopoietic progenitor stem cell collection by mobilization with plerixafor followed by apheresis vs bone marrow harvest in patients with sickle cell disease in the multi-center HGB-206 trial. Am J Hematol E239–E242. https://doi.org/10.1002/ajh.25867.
6. Palmer J, McCune JS, Perales M-A, et al. (2016) Personalizing Busulfan-Based Conditioning: Considerations from the American Society for Blood and Marrow Transplantation Practice Guidelines Committee. Biol Blood Marrow Transplant 1915–1925. https://doi.org/10.1016/j.bbmt.2016.07.013
7. Brunson A, Keegan THM, Bang H, et al. (2017) Increased risk of leukemia among sickle cell disease patients in California. Blood 130:1597–1599. doi: 10.1182/blood-2017-05-783233.
8. Seminog OO, Ogunlaja OI, Yeates D, Goldacre MJ (2016) Risk of individual malignant neoplasms in patients with sickle cell disease: English national record linkage study. J R Soc Med 109:303–309. doi: 10.1177/0141076816651037.

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/LCA/LCD): N/A