BlueCross BlueShield of Tennessee Medical Policy Manual

Agalsidase Beta (Fabrazyme®)


58468-0041-XX FABRAZYME 5MG Solution Reconstituted (GENZYME)

58468-0040-XX FABRAZYME 35MG Solution Reconstituted (GENZYME)


Agalsidase beta is a recombinant DNA origin form of human α-galactosidase A, a lipid degrading enzyme. It has the same amino acid sequence as the native enzyme.  It is used to treat Fabry disease, deficiency of the enzyme α-galactosidase A.  

Fabry disease is an X-linked recessive inborn error of glycosphingolipid metabolism with an estimated frequency of about 1 in 50,000 births.  The result of this mutation is progressive accumulation of glycosphingolipids in cellular lysosomes of multiple body tissues.  Clinical manifestations typically begin in childhood and may include abdominal or flank pain simulating appendicitis or renal colic, angiokeratomas, hypohidrosis, corneal and lenticular opacities, vascular disease of the kidney, heart, and brain, intolerance to heat, cold, and exercise, mild proteinuria, gastrointestinal problems, and acroparesthesias.  Fabry crises, lasting from minutes to several days, consist of agonizing, burning pain in the hands, feet, and proximal parts of the extremities.  Affected individuals have a lifespan of 30 to 50 years, typically resultant from renal failure, hypertrophic cardiomyopathy, myocardial infarction or cerebrovascular accidents.  Female carriers may be asymptomatic or may exhibit severe manifestations similar to males with classic disease.

Enzyme replacement therapy for Fabry disease with agalsidase beta has been shown to provide an exogenous source of α-galactosidase A.  It can reverse histologic abnormalities as well as improve some clinical manifestations of the disease.


·         Agalsidase beta for the treatment of Fabry disease is considered medically necessary if the medical appropriateness criteria are met (See Medical Appropriateness below.)

·         Agalsidase beta for the treatment of other conditions/diseases is considered investigational.



·         Patient is at least 2 years of age; AND

Universal Criteria

·         Must not be used in combination with migalastat; AND

Fabry Disease (alpha-galactosidase A deficiency)

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

·         Baseline value for plasma GL-3 and/or GL-3 inclusions


·         Patient continues to meet universal and other indication-specific relevant criteria such as concomitant therapy requirements (not including prerequisite therapy), performance status, etc. identified in Initial Approval Criteria; AND

·         Absence of unacceptable toxicity from the drug. Examples of unacceptable toxicity include the following: anaphylaxis and severe hypersensitivity reactions, severe infusion-associated reactions, compromised cardiac function, etc.; AND

·         Disease response with treatment as defined by a reduction in plasma GL-3 and/or GL-3 inclusions compared to pre-treatment baseline




Fabry Disease

1 mg/kg of body weight infused every two weeks as an intravenous (IV) infusion.


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


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

·         115 billable units every 14 days


BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.


We develop Medical Policies to provide guidance to Members and Providers.  This Medical Policy relates only to the services or supplies described in it.  The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy.  For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed.  If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.


For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).


1.     Fabrazyme [package insert].-Cambridge, MA; Genzyme Corporation.; March 2021. Accessed April 20, 2021.

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. GeneReviews. (Accessed on September 6, 2017).

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.     Brandon 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.     Banikazemi M, Bultas J, Waldek S, et al. Agalsidase-beta therapy for advanced Fabry disease: a randomized trial. 2007 Jan 16;146(2):77-86. doi: 10.7326/0003-4819-146-2-200701160-00148. Epub 2006 Dec 18.

10.  Wraith E, Tylki-Szymanska A, Guffon N, et al. Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease. J Pediatr. 2008 Apr;152(4):563-70, 570.e1. doi: 10.1016/j.jpeds.2007.09.007. Epub 2007 Dec 3.

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.  Lexi-Comp Online. (2021, February). AHFS DI. Agalsidase beta. Retrieved April 20, 2021 from Lexi-Comp Online with AHFS.

13.  MICROMEDEX Healthcare Series. Drugdex Drug Evaluations. (2021, March). Agalsidase beta. Retrieved April 20, 2021 from MICROMEDEX Healthcare Series.




Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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