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Agalsidase beta (Fabrazyme®)
MA08.033c

Policy

MEDICALLY NECESSARY

Agalsidase beta (Fabrazyme®) is considered medically necessary and, therefore, covered for individuals two years of age and older with Fabry disease to reduce globotriaosylceramide (GL-3) deposition in the capillary endothelium of the kidney and certain other cell types when all of the following are met, including dosing and frequency:
  • Diagnosis is confirmed by one of the following:
    • Deficiency of alpha-galactosidase A in plasma or peripheral leukocytes
    • Confirmation of a hemizygous pathogenic variant(s) in the GLA gene
  • Dosing and frequency: 1 mg/kg IV infusion every 2 weeks
  • No concomitant use of migalastat (Galafold™)
EXPERIMENTAL/INVESTIGATIONAL

All other uses of agalsidase beta (Fabrazyme®) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

DOSING AND FREQUENCY REQUIREMENTS
The Company reserves the right to modify the Dosing and Frequency Requirements listed in this policy to ensure consistency with the most recently published recommendations for the use of agalsidase beta (Fabrazyme®). Changes to these guidelines are based on a consensus of information obtained from resources such as, but not limited to: the US Food and Drug Administration (FDA); Company-recognized authoritative pharmacology compendia; or published peer-reviewed clinical research. The professional provider must supply supporting documentation (i.e., published peer-reviewed literature) in order to request coverage for an amount of agalsidase beta (Fabrazyme®) outside of the Dosing and Frequency Requirements listed in this policy. For a list of Company-recognized pharmacology compendia, view our policy on off-label coverage for prescription drugs and biologics.

Accurate member information is necessary for the Company to approve the requested dose and frequency of this drug. If the member’s dose, frequency, or regimen changes (based on factors such as changes in member weight or incomplete therapeutic response), the provider must submit those changes to the Company for a new approval based on those changes as part of the utilization management activities. The Company reserves the right to conduct post-payment review and audit procedures for any claims submitted for agalsidase beta (Fabrazyme®).

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

When coverage of agalsidase beta (Fabrazyme®) is requested outside of the Dosing and Frequency Requirements listed in this policy, the prescribing professional provider must supply documentation (i.e., published peer-reviewed literature) to the Company that supports this request.

Guidelines

There is no Medicare coverage determination addressing this drug; therefore, the Company policy is applicable.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, agalsidase beta (Fabrazyme®) may be covered under the medical benefits of the Company’s Medicare Advantage products when medical necessity criteria including dosing and frequency requirements listed in the medical policy are met.

Certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when agalsidase beta (Fabrazyme®) is covered under a member's medical benefit (Part B benefit). It does not address instances when agalsidase beta (Fabrazyme®) is covered under a member’s pharmacy benefit (Part D benefit).

DRUG ADMINISTRATION

Per the FDA labeling, the recommended dosage of agalsidase beta (Fabrazyme®) is 1 mg/kg body weight administered every two weeks as an intravenous infusion.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

The FDA's initial approval of agalsidase beta (Fabrazyme®) was issued on April 24, 2003 for the treatment of Fabry disease.

Description

Fabry disease is a rare gene mutation disorder that is inherited in an X-linked recessive pattern. Because the altered gene is carried on a mother’s X chromosome, sons have a fifty percent chance of inheriting the disorder, and daughters have a fifty percent chance of being a carrier. Some female carriers may also exhibit symptoms, especially cloudiness of the cornea.

This mutation causes a deficiency of the lysosomal enzyme known as alpha-galactosidase A. The lack of this enzyme causes an insufficient breakdown of lipids (fats), which then build up to harmful levels in the eyes, kidneys, autonomic nervous system, and cardiovascular system. Symptoms, which usually begin during childhood or adolescence, include the following:
  • Generalized fatigue and weakness
  • Burning sensation in the hands that worsens with exercise and hot weather
  • Small, raised, red-purple blemishes on the skin
  • Decreased sweating
  • Fever
  • Gastrointestinal difficulties, particularly after eating
Although Fabry disease usually presents in childhood, a diagnosis may not be confirmed until considerable organ damage has occurred. The average age of diagnosis is about 30. Diagnosis is confirmed by low or absent alpha-galactosidase A activity in plasma or serum, leukocytes, tears, biopsied tissues, or cultured skin fibroblasts. Because of the delay in diagnosis, the increased lipid storage may lead to impaired arterial circulation and an increased risk of heart attack or stroke. The heart may also become enlarged, and the kidneys may become progressively damaged.

Treatment of Fabry disease was initially limited to some oral medications (e.g., carbamazepine [Tegretol®], phenytoin [Dilantin®], and metoclopramide [Reglan®]) that were prescribed for an individuals' specific symptoms. In the past few years, agalsidase beta (Fabrazyme®) was developed through recombinant DNA technology and was approved by the US Food and Drug Administration, on April 24, 2003, as an orphan drug (a drug used to treat, prevent, or diagnose a rare disease) for treatment in individuals with Fabry disease. Agalsidase beta (Fabrazyme®) is almost identical to alpha-galactosidase A. The replacement of the missing lysosomal enzyme reduces globotriaosylceramide (GL-3), a type of lipid that accumulates in many types of cells, including blood vessels in the kidneys and other organs. With the reduction of fat deposition, it is believed that life-threatening organ damage will be prevented.

CLINICAL STUDIES

The FDA approval of agalsidase beta (Fabrazyme®) was based on the results of five clinical studies in individuals with Fabry disease. Study 1 was a randomized, double-blind, placebo-controlled, multi-national, multi-center study of 58 individuals, ages 16-61 years, who have a diagnosis of Fabry disease and are naive to enzyme replacement therapy. For five months, individuals received either agalsidase beta (Fabrazyme®) or placebo every two weeks. The primary efficacy endpoint was assessing GL-3 inclusion in renal interstitial capillary endothelial cells by light microscopy and grading on an inclusion severity scale ranging from 0 (normal or near normal) to 3 (severe inclusions). There was a statistically significant reduction in the inclusion of GL-3 in the Fabrazyme-treated group compared to the placebo-treated group; 69% of the Fabrazyme group achieved a score of 0 compared to the placebo group with none of the individuals reaching a score of 0. These similar reductions were also observed in the capillary endothelium of the heart and the skin.

Study 2 was a randomized, double-blind, placebo-controlled, multinational, multicenter study of 82 individuals, ages 20 to 72 years, who have a diagnosis of Fabry disease and are naive to enzyme replacement therapy. Individuals received either agalsidase beta (Fabrazyme®) or placebo every two weeks up to a maximum of 35 months. The reduction in plasma GL-3 levels in the Fabrazyme group compared to the placebo group was statistically significant at one year and at two years.

Study 3 was an open-label, uncontrolled, multi-national, multi-center study evaluating safety, pharmacokinetics, and pharmacodynamics of agalsidase beta (Fabrazyme®) in 16 pediatric individuals with Fabry disease, ages 8 to 16 years at first treatment. All individuals received agalsidase beta (Fabrazyme®) every two weeks for up to 48 weeks. At baseline all the males had elevated plasma GL-3 levels. Twelve of the 12 males had observed GL-3 inclusions in the the capillary endothelium on skin biopsies. At week 24 and 48 the 12 males with GL-3 inclusions in capillary endothelium at baseline achieved a GL-3 inclusion score of 0.

Study 4 was an open-label, re-challenge study to evaluate the safety of agalsidase beta (Fabrazyme®) in individuals who had a positive skin test to agalsidase beta (Fabrazyme®) or who had tested positive for agalsidase beta (Fabrazyme®) specific IgE antibodies. Six adult males, who had experienced multiple or recurrent infusion reactions during a previous clinical trials with agalsidase beta (Fabrazyme®), were re-challenged with agalsidase beta (Fabrazyme®) administered as a graded infusion for up to 52 weeks of treatment. Four of the six individuals treated received at least 26 weeks of agalsidase beta (Fabrazyme®). Two individuals discontinued prematurely due to recurrent infusion reactions.

Study 5 was an observational study that analyzed 24 Fabrazyme-treated pediatric individuals with Fabry disease aged 2 to <8 years at Fabrazyme initiation and with elevated plasma GL-3 levels (i.e., >7.03 μg/mL) at baseline, plasma GL-3 levels fell within the normal range (i.e., ≤7.03 μg/mL) in 91% (20/22), 95% (18/19), and 92% (12/13) of individuals​ at 6, 12, and 24 months, respectively. Common adverse reactions reported were upper respiratory tract infection, chills, pyrexia, headache, cough, paresthesia, fatigue, peripheral edema, dizziness, and rash. 

The safety and effectiveness of Fabrazyme have been established in pediatric individuals based on adequate and well-controlled studies in adults, a single-arm, open-label study in 16 pediatric individuals with Fabry disease aged 8 to 16 years, and additional data in 24 individuals​ with Fabry disease aged 2 to 7 years​. 


Enzyme replacement therapy has been approved by the United States Food and Drug Administration for the treatment of Fabry disease. This therapy can ease pain, improve organ function, and reduce lipid storage. The National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH), continues to support research to find ways to treat and prevent lipid storage diseases such as Fabry disease.

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

Agalsidase beta. American Hospital Formulary Service (AHFS). Drug Information 2021. [Lexicomp Web site]. 02/26/2021. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 11, 2022.

Banikazemi M, Desnick RJ, Astrin KH. Fabry disease. [eMedicine Web site]. 08/23/2018. Available at: http://www.emedicine.com/ped/topic2888.htm. Accessed March 11, 2022..

Elsevier’s Clinical Pharmacology Compendium. Agalsidase beta. [Clinical Pharmacology Web site]. 03/22/2021. Available at: http://online.lexi.com/lco/action/home#.. [via subscription only]. Accessed March 11, 2022.

Genzyme Corporation. Fabrazyme site index. [Fabrazyme Web site]. 03/2021 Available at: https://www.fabrazyme.com/. Accessed March 11, 2022.

Lexi-Drugs Compendium. Agalsidase beta. [Lexicomp Online Web site]. 03/04/2022. Available at:​ http://online.lexi.com/lco/action/home [via subscription only]. Accessed March 11, 2022.

Lidove O, Joly D, Barbey F, et al. Clinical results of enzyme replacement therapy in Fabry disease: a comprehensive review of literature. Int J Clin Pract. 2007;61(2):293-302. Also available on the Wiley InterScience Web site at: http://www.blackwell-synergy.com/doi/pdf/10.1111/j.1742-1241.2006.01237.x. Accessed March 11, 2022.

Mandava P. Overview of Fabry Disease.[Medscape Website]. 08/28/2018. Available at: http://emedicine.medscape.com/article/1952086-overview#showall. Accessed March 11, 2022.

Mehta, A, Hughes, DA. GeneReviews® [Internet]. 08/05/2000; updated 01/05/2017​​. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1292/?report=reader Accessed March 11, 2022.

Micromedex® Healthcare Series. Agalsidase beta. Greenwood Village, CO: Truven Health Analytics. 11/06/2021​. Available at: http://www.micromedexsolutions.com [via subscription only]. Accessed March 11, 2022.

National Institute of Neurological Disorders and Stroke (NINDS). NINDS Fabry disease information page. [NINDS Web site]. 03​/27/2019. Available at: http://www.ninds.nih.gov/disorders/fabrys/fabrys.htm. Accessed March 11, 2022.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Drugs @ FDA. Fabrazyme. [FDA Web site].03/11/2021. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search. Accessed March 11, 2022.

US Food and Drug Administration (FDA). Fabrazyme® (agalsidase beta) prescribing information. [FDA Web site]. March 2021. Available at:http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103979s5135lbl.pdfAccessed March 11, 2022.​

Coding

CPT Procedure Code Number(s)
N/A

ICD - 10 Procedure Code Number(s)
N/A

ICD - 10 Diagnosis Code Number(s)
E75.21 Fabry (-Anderson) disease

HCPCS Level II Code Number(s)
J0180 Injection, agalsidase, beta, 1 mg

Revenue Code Number(s)
N/A




Coding and Billing Requirements


Policy History

8/30/2021
8/30/2021
4/6/2022
MA08.033
Medical Policy Bulletin
Medicare Advantage
No