Medicare Advantage
Advanced Search

Alglucosidase alfa (e.g., Lumizyme®), Avalglucosidase alfa-ngpt (Nexviazyme® )
MA08.036f

Policy

MEDICALLY NECESSARY

ALGLUCOSIDASE ALFA (LUMIZYME®) 
Alglucosidase alfa (Lumizyme®) is considered medically necessary and, therefore, covered for the treatment of symptomatic individuals one month of age and older with infantile-onset or juvenile/adult-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) when all of the following criteria are met, including dosing and frequency:
  • Diagnosis is confirmed by either of the following:
    • Deficiency of acid alpha-glucosidase in leukocytes or skin fibroblasts or muscles
    • Confirmation of biallelic pathogenic variant(s) in the GAA gene.
  • Dosing and frequency: infants one month of age and older, children, adolescents and adult dosing IV: 20 mg/kg every 2 weeks.
AVALGLUCOSIDASE ALFA-NGPT (NEXVIAZYME®)
Avalglucosidase alfa-ngpt (Nexviazyme®) is considered medically necessary and, therefore, covered for the treatment of individuals one year of age and older​ with late-onset Pompe disease​ (lysosomal acid alpha-glucosidase [GAA] deficiency) when all of the following criteria are met, including dosing and frequency:
  • The participant has confirmed acid alpha-glucosidase (GAA) enzyme deficiency from any tissue source (e.g., skin, fibroblasts, muscle, or blood) and/or 2 confirmed GAA gene mutations.​​
  • Dosing and frequency: 
    • ≥30 kg, the recommended dosage is 20 mg/kg (of actual body weight) every two weeks. 
    • <30 kg, the recommended dosage is 40 mg/kg (of actual body weight) every two weeks.
EXPERIMENTAL/INVESTIGATIONAL

All other uses of alglucosidase alfa (Lumizyme®) and avalglucosidase alfa-ngpt (Nexviazyme®) 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 alglucosidase alfa (Lumizyme®) and avalglucosidase alfa-ngpt (Nexviazyme®) . 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 alglucosidase alfa (Lumizyme®) and avalglucosidase alfa-ngpt (Nexviazyme®) 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 alglucosidase alfa (Lumizyme®) and avalglucosidase alfa-ngpt (Nexviazyme®).

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 alglucosidase alfa (Lumizyme®) or avalglucosidase alfa-ngpt (Nexviazyme®)​ 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

Per the US Food and Drug Administration (FDA)--approved labeling, the recommended dosing and frequency of alglucosidase alfa (Lumizyme®) is 20 mg per kg​ weight administered by intravenous (IV) infusion every two weeks.

Per the US Food and Drug Administration (FDA)--approved labeling, the recommended dosing and frequency of (Nexviazyme) avalglucosidase alfa-ngpt​ is 1 mg per kg of body weight administered once weekly as an intravenous infusion.

BLACK BOX WARNING

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, alglucosidase alfa (Lumizyme®) and avalglucosidase alfa-ngpt (Nexviazyme®) are covered under the medical benefits of the Company’s products when the medical necessity criteria including dosing and frequency requirements listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

On May 10, 2010, under a priority review, the FDA approved alglucosidase alfa (Lumizyme®) as an orphan drug.

On August 26, 2021, under a priority review, the FDA approved avalglucosidase alfa-ngpt (Nexviazyme​) as an orphan drug.

PEDIATRIC USE

The safety and effectiveness of alglucosidase alfa (Lumizyme®) have not been established in individuals younger than one month of age.

The safety and effectiveness of avalglucosidase alfa-ngpt (Nexviazyme®) have not been established in individuals younger than one​ year of age.

Description

Pompe disease is a rare genetic disorder of glycogen metabolism that is caused by the absence or marked deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). This disease is also known as glycogen storage disease type II, GSD II, glycogenosis type II, or acid maltase deficiency. GAA is necessary for proper muscle functioning and is used by the heart and muscle cells to convert a form of sugar called glycogen into energy. Without the GAA enzyme action, glycogen builds up in the cells of the heart, skeletal muscles, and hepatic tissues. Ultimately, these body organs are weakened by the intralysosomal accumulation of glycogen. Pompe disease encompasses a range of phenotypes, each including myopathy, but with significant variability in the age of onset, organ involvement, and clinical severity.

Infantile-onset Pompe disease occurs in an estimated 1 in every 40,000 to 300,000 births. Symptoms begin in the first months of life, with feeding problems, poor weight gain, muscle weakness, floppiness, and head lag. The primary symptom is heart and skeletal muscle weakness, which leads to the development of cardiomyopathy, progressing respiratory weakness, and death, usually from respiratory failure. Younger individuals generally have a much more aggressive form of the disease.

Juvenile/adult-onset Pompe disease results in intralysosomal accumulation of glycogen that is limited primarily to skeletal muscle, resulting in progressive muscle weakness. The onset can be as early as the first decade of childhood or as late as the sixth decade of adulthood.  The primary symptom is muscle weakness progressing to respiratory weakness and death from respiratory failure over several years.  The heart is usually spared. 

Enzyme replacement therapy has been shown to decrease heart size, maintain normal heart function, improve muscle function, tone, and strength, and reduce glycogen accumulation. Enzyme replacement therapy is currently not recommended for individuals with no symptoms or objective signs (proximal muscle weakness or reduced FVC in wither upright or supine position) of Pompe disease.

Alglucosidase alfa (Lumizyme®) is FDA-approved for individuals with Pompe disease (GAA deficiency). The safety and efficacy was assessed in 57 treatment-naïve individuals with infantile-onset Pompe disease, aged 0.2 months to 3.5 years at first infusion, in three separate clinical trials. In all three trials ventilator-free survival improved significantly compared with an untreated historical control. The safety and efficacy of alglucosidase alfa (Lumizyme®) was also assessed in 90 individuals with juvenile/adult-onset Pompe disease in a randomized, double-blinded, placebo-controlled trial. Alglucosidase alfa (Lumizyme®) was shown to have a significant increase in forced vital capacity (FVC) and the distance an individual with juvenile/adult-onset Pompe disease can walk within 6 minutes (6 minute walk test).

Avalglucosidase alfa-ngpt (Nexviazyme®) is a hydrolytic lysosomal glycosaminoglycan (GAG)-specific enzyme is FDA approved for individuals with Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy syndrome).

The safety analysis was pooled from four clinical trials (mean exposure of 26 months, up to 85 months of treatment) included a total of 141 Nexviazyme-treated individuals (118 adult and 23 pediatric individuals). Serious adverse reactions reported in two or more individuals treated​  with Nexviazyme were: respiratory distress, chills, and pyrexia. Serious adverse events were similar across both adult and pediatric populations. A total of five Nexviazyme-treated individuals in clinical trials permanently discontinued Nexviazyme​ due to adverse reactions, including two of these individuals​ who discontinued the treatment because of a serious adverse reaction. The most frequently reported adverse reactions (>5%) in the pooled safety population were: headache, diarrhea, nausea, fatigue, arthralgia, myalgia, dizziness, rash, vomiting, pyrexia, abdominal pain, pruritus, erythema, abdominal pain upper, chills, cough, urticaria, dyspnea, hypertension, and hypotension. 


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

American Hospital Formulary Service (AHFS). Drug Information 2014. Alglucosidase alfa. [Lexicomp Web site]. Updated 02/26/2021. Available at:http://online.lexi.com/lco/action/home[via subscription only]. Accessed August 26, 2021.

Cupler E, Berger K, et al. Consensus treatment recommendations for late-onset Pompe disease. Muscle Nerve. 2012;45(3):319-333.

Elsevier’s Clinical Pharmacology Compendium. Agalsidase alfa. [Clinical Pharmacology Web site]. 08/11/2014. Available at:http://online.lexi.com/lco/action/home#.. [via subscription only]. Accessed August 26, 2021.

Elsevier’s Clinical Pharmacology Compendium. Agalsidase alfa-ngpt​. [Clinical Pharmacology Web site]. 08/11/2021. Available at:http://online.lexi.com/lco/action/home#.. [via subscription only]. Accessed August 26, 2021.

Genzyme Corp. Alglucosidase alfa (Lumizyme®) [prescribing Information]. Cambridge, MA: Genzyme: 2014. Updated 02/2020. Available at: http://www.lumizyme.com/~/media/LumizymeUS/Files/lumizyme_prescribing_information.pdf. Accessed August 26, 2021.

Genzyme Corp. avalglucosidase alfa-ngpt (Nexviazyme®)​ [prescribing Information]. Cambridge, MA: Genzyme: 2021. Updated 08/2021. Available at: nexviazyme.pdf (sanofi.us)​​. Accessed August 26, 2021.​​​

Kishnani PS, Corzo D, Nicolino M, et al. Recombinant human acid [alpha]-glucosidase: Major clinical benefits in infantile-onset Pompe disease. Neurology. 2007;68(2):99-109.

Kruer MC, Lysosomal Storage Disease.eMedicine[eMedicine Web site] updated 12/09/2015. Available at: http://emedicine.medscape.com/article/1182830-overview. Accessed August 26, 2021.

LaCana E, Yao LP, Pariser AR. The role of immune tolerance induction in​ restoration of the efficacy of ERT in Pompe disease. Am J Med Genet C Semin Med Genet. 2012;160(1):30-9.

Leslie N, Bailey L GeneReviews® [Internet]. 08/31/2007; updated 05/11/2017. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1261/#gsd2.Diagnosis. Accessed August 26, 2021.

Lexi-Drugs Compendium. Alglucosidase alfa. [Lexicomp Online Web site]. 08/11/21. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 26, 2021.

Lexi-Drugs Compendium. Alglucosidase alfa-ngpt​​​. [Lexicomp Online Web site]. 08/09​/21. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 26, 2021.

Micromedex®. Alglucosidase alfa. [Micromedex Web site]. 09/14/2020. Available at: http://www.micromedexsolutions.com/micromedex2/librarian/ [via subscription only]. Accessed August 26, 2021.

National Institute of Neurological Disorders and Stroke (NINDS). NINDS Pompe disease information page. [NINDS Web site]. Available at: Pompe Disease Information Page | National Institute of Neurological Disorders and Stroke (nih.gov). Accessed August 26, 2021.

Prater SN, Banugaria SG, Dearmey SM, et al. The emerging phenotype of long-term survivors with infantile Pompe disease. Genet Med. 2012;14(9):800-10.

US Food and Drug Administration (FDA). Alglucosidase alfa (Lumizyme®) SUPPLEMENT APPROVAL. Release REMS Requirement. [FDA Web site]. 08/01/2014. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/125291Orig1s136ltr.pdf. Accessed August 26, 2021.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Alglucosidase alfa (Lumizyme®). Product approval information. [FDA Web site]. May 24, 2010. Updated 02/18/2020.Available at: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2010/125291s000ltr.pdf. Accessed August 26, 2021​.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Avalglucosidase alfa-ngpt (Nexviazyme®)​. Product approval information. [FDA Web site]. August 06, 2021. Updated 02/18/2020.Available at: http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2010/125291s000ltr.pdf. Accessed August 26, 2021​.

van der Ploeg A, Clemens P, et al. A randomized study of alglucosidase in late-onset Pompe's disease. New Engl J Med. 2010;362(15):1396-1406.​

Coding

CPT Procedure Code Number(s)
N/A

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

ICD - 10 Diagnosis Code Number(s)
E74.02 Pompe disease

HCPCS Level II Code Number(s)
MEDICALLY NECESSARY
J0219Injection, avalglucosidase alfa-ngpt, 4 mg
J0221Injection, alglucosidase alfa, (Lumizyme), 10 mg​


NOT ELIGIBLE FOR REIMBURSEMENT
J0220Injection, alglucosidase alfa, 10 mg, not otherwise specified



Revenue Code Number(s)
N/A



Coding and Billing Requirements


Policy History

4/1/2022
5/4/2022
MA08.036
Medical Policy Bulletin
Medicare Advantage
No