Last Review Date: 02/01/2024

Date of Origin: 06/01/2023

Dates Reviewed: 06/2023, 02/2024

1. Length of Authorization

Coverage will be provided for 12 months and may be renewed.

2. Dosing Limits

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

• Elfabrio 20 mg/10 mL single-dose vial for injection: 6 vials every 14 days

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

• 120 billable units (120 mg) every 14 days

3. Initial Approval Criteria ¹

Coverage is provided in the following conditions:

• Patient is at least 18 years of age; AND

Universal Criteria

• Must not be used in combination with migalastat or agalsidase beta; AND

Fabry Disease (alpha-galactosidase A deficiency) † ^1,3,7,13

• Documented diagnosis of Fabry disease with biochemical/genetic confirmation by one of the following:

• Deficiency in α-galactosidase A (α-Gal A) activity in plasma, isolated leukocytes, and/or cultured cells (males only); OR
• Detection of pathogenic mutations in the GLA gene by molecular genetic testing; AND

• Patient has a baseline value for at least one of the following:
  • Tissue globotriaosylceramide (Gb3/GL-3) inclusions
  • Plasma or urinary globotriaosylceramide (Gb3/GL-3) or globotriaosylsphingosine (lyso-Gb3)
    • • Clinical signs and/or symptoms of disease (e.g., dermatologic, gastrointestinal, pulmonary, vascular, renal, cardiac, neurologic manifestations)

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

4. Renewal Criteria ^1,3,13

Coverage can be renewed based on the following criteria:

• Patient continues to meet the universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in section III; AND

• Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include: anaphylaxis and severe hypersensitivity reactions, severe infusion-associated reactions, glomerulonephritis, etc.; AND
  • •  
  • Disease response with treatment as defined by a reduction or stabilization in one or more of the following, as compared to pre-treatment baseline:

• •  
  • Tissue globotriaosylceramide (Gb3/GL-3) inclusions
  • Plasma or urinary globotriaosylceramide (Gb3/GL-3) or globotriaosylsphingosine (lyso-Gb3); OR
    •  
  • Disease response with treatment as defined by an improvement or stabilization of clinical signs and/or symptoms (e.g., dermatologic, gastrointestinal, pulmonary, vascular, renal, cardiac, neurologic manifestations)

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS Code:

• J2508 – Injection, pegunigalsidase alfa-iwxj, 1 mg; 1 billable unit = 1 mg

NDC:

• Elfabrio 20 mg/10 mL single-dose vial for injection: 10122-0160-xx

7. References

1. Elfabrio [package insert]. Parma, Italy; Chiesi Farmaceutici S.p.A.; May 2023. Accessed January 2024.
2. Mehta A, Beck M, Eyskens F, et al. Fabry disease: a review of current management strategies. QJM. 2010 Sep; 103(9):641-59.
3. Mehta A, Hughes DA. Fabry Disease. In: Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews®. [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Initial Posting: August 5, 2002; Last Update: March 09, 2023. Accessed on December 20, 2023. https://www.ncbi.nlm.nih.gov/books/NBK1292/.
4. Biegstraaten M, Arngrímsson R, Barbey F, et al. Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document. Orphanet J Rare Dis. 2015 Mar 27;10:36.
5. Hopkin RJ, Jefferies JL, Laney DA, et al. The management and treatment of children with Fabry disease: A United States-based perspective. Mol Genet Metab. 2016 Feb;117(2):104-13.
6. Laney DA, Bennett RL, Clarke V, et al. Fabry disease practice guidelines: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2013 Oct;22(5):555-64.
7. Kes VB, Cesarik M, Zavoreo I, et al. Guidelines for diagnosis, therapy and follow up of Anderson-Fabry disease. Acta Clin Croat. 2013 Sep;52(3):395-405.
8. Branton MH, Schiffmann R, Sabnis SG, et al. Natural history of Fabry renal disease: influence of alpha-galactosidase A activity and genetic mutations on clinical course. Medicine (Baltimore). 2002 Mar;81(2):122-38.
9. Schiffmann R, Goker-Alpan O, Holida M, et al. Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1-year Phase 1/2 clinical trial. J Inherit Metab Dis. 2019 May;42(3):534-544. doi: 10.1002/jimd.12080. Epub 2019 Apr 8. PMID: 30834538.
10. Germain DP, Fouilhoux A, Decramer S, Tardieu M, Pillet P, Fila M, Rivera S, Deschênes G, Lacombe D. Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients. Clin Genet. 2019;96:107-17. [PubMed]
11. Eng CM, Guffon N, Wilcox WR, et al; International Collaborative Fabry Disease Study Group. Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease. N Engl J Med. 2001 Jul 5;345(1):9-16. doi: 10.1056/NEJM200107053450102.
12. Henderson N, Berry L, Laney DA. Fabry Disease practice resource: Focused revision. J Genet Couns. 2020 Oct;29(5):715-717. doi: 10.1002/jgc4.1318.
13. Mauer M, Kopp JB, Wallace E. (2022). Fabry disease: Clinical features and diagnosis. In Curhan GC, Glassock RJ (Eds.), UptoDate. Last updated: July 20, 2023. Accessed on January 2, 2024. Available from https://www.uptodate.com/contents/fabry-disease-clinical-features-and-diagnosis.
14. Henderson N, Berry L, Laney DA. (2020) Fabry Disease practice resource: Focused revision. 29(5): 715-717.
15. Dawn A. Laney, Robin L. Bennett, Virginia Clarke, Angela Fox, Robert J. Hopkin, Jack Johnson, Erin O’Rourke, Katherine Sims, Gerald Walter (2013) Fabry Disease Practice Guidelines: Recommendations of the National Society of Genetic Counselors. Journal of Genetic Counseling, 22(5): 555-564. https://doi.org/10.1007/s10897-013-9613-3.

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