Coverage Policy Manual
Policy #: 2020030
Category: Pharmacy
Initiated: March 2021
Last Review: December 2023
  Alglucosidase alfa (e.g., Lumizyme™)
Description:
Pompe disease is a rare autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase (GAA), an enzyme that degrades lysosomal glycogen which presents as a wide spectrum ranging from the severe rapidly progressive infantile-onset form to a more slowly progressive late-onset form. The American College of Medical Genetics (ACMG) Work Group on Management of Pompe Disease (2006) developed algorithms to diagnose and manage both types of Pompe disease. The level of residual activity of the GAA enzyme drives Pompe disease severity and age of symptoms onset. GAA gene sequencing may be used to confirm a diagnosis or when there are discordant GAA enzyme activity studies (American Association of Neuromuscular and Electrodiagnostic Medicine [AANEM] 2009).
 
Alglucosidase alfa is an enzyme replacement therapy (ERT) specific to Pompe’s disease. This ERT provides an exogenous source of GAA. Binding to mannose-6-phosphate receptors on the cell surface has been shown to occur via carbohydrate groups on the GAA molecule, after which it is internalized and transported into lysosomes, where it undergoes proteolytic cleavage that results in increased enzymatic activity. It then exerts enzymatic activity in cleaving glycogen.
 
Regulatory Status
 
Alglucosidase alfa (e.g., Lumizyme™) was approved by the U.S. Food and Drug Administration (FDA) in 2010 for individuals with Pompe disease (GAA deficiency).   
 
Coding
 
See CPT/HCPCS Code section below.
Policy/
Coverage:
Effective March 11, 2021, Prior Approval is required for Alglucosidase alfa.
 
The initial use of this drug requires documentation of direct physician involvement and signature in the ordering and evaluation as documented in the medical records submitted for prior approval. Concurrent review will require continued evidence of appropriate physician involvement.    
 
Effective December 19, 2023
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Alglucosidase alfa meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for Pompe when the following criteria are met:
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months
 
Infantile Onset Pompe Disease (ACMG, 2017)
 
1. Individual has a diagnosis of infantile-onset Pompe disease; AND
2. Individual has an absence or deficiency (< 1% of normal mean) GAA activity in skin fibroblasts OR biallelic deletion or mutation in GAA gene (documentation must be submitted); AND
3. Individual is experiencing disease symptoms (respiratory and/or skeletal muscle weakness;) OR
4. Individual has confirmed evidence of cardiac hypertrophy; AND
5. Prescribed by, or in consultation with, a neurologist or specialist in Pompe disease.
6. Will not be used concomitantly with other enzyme replacement therapies (e.g., avalglucosidase alfa, cipaglucosidase alfa); AND
7. Must be dosed in accordance with the FDA label.
 
Late Onset Pompe Disease  (ACMG, 2006, FDA label 2014; AANEM2009)
 
1. Individual has a diagnosis of late-onset Pompe disease (LOPD) as evidenced by ONE of the following:
a. Enzyme assay showing a deficiency (< 40% of normal mean) of acid alpha-glucosidase (GAA) activity in the blood, skin, or muscle; AND
b. Genetic testing showing a mutation in the GAA gene (documentation must be submitted); AND  
2. Individual has measurable signs of Pompe disease, such as impairment in pulmonary function or motor weakness (when applicable, baseline results documentation of percent predicted forced vital capacity (FVC) and 6-minute walk test (6MWT) is required); AND
3. Prescribed by, or in consultation with, a neurologist or specialist in Pompe disease; AND
4. Will not be used in the following circumstances:
a. Concomitantly with another ERT for Pompe disease (e.g., avalglucosidase alfa-ngpt or cipaglucosidase alfa-atga); AND
b. Individual requires invasive ventilation; AND
5. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL– no more than 12 months
 
1. Individual has experienced a positive clinical response to therapy as evidenced by an improvement or stabilization in percent predicted FVC and/or 6-MWT; AND  
2. Must be dosed in accordance with FDA labeling; AND
3. Will not be used concomitantly with other enzyme replacement therapies, (e.g., avalglucosidase alfa or cipaglucosidase alfa-atga).
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended dose of Alglucosidase alfa is 20 mg/kg administered once every two weeks as an intravenous infusion.
 
Alglucosidase alfa is available as a 50 mg powder in a single-dose vial for reconstitution.
 
Alglucosidase alfa should be administered by a healthcare professional.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Alglucosidase alfa, for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of Alglucosidase alfa, for any indication or circumstance not described above, is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective March 1, 2022 to December 18, 2023
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Alglucosidase alfa meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for Pompe disease when dosed in accordance with FDA labeling and the following criteria are met:
 
Initial Approval (6 months)
 
Infantile onset (ACMG, 2017)
    1. Has a diagnosis of infantile-onset Pompe disease AND
    2. Member has an absence or deficiency (<1% of normal mean) GAA activity in skin fibroblasts OR biallelic deletion or mutation in GAA gene (documentation must be submitted) AND
    3. Member is experiencing disease symptoms (respiratory and/or skeletal muscle weakness) OR
    4. Member has confirmed evidence of cardiac hypertrophy AND
    5. Prescribed by, or in consultation with, a neurologist or specialist in Pompe disease.
    6. Will not be used concomitantly with avalglucosidase alfa AND
    7. Must be dosed in accordance with the FDA label.
 
Non infantile onset (Late onset)  (ACMG, 2006, FDA label 2014; AANEM2009)
    1. Has a diagnosis of late-onset Pompe disease with clinical manifestations. AND
    2. Member has an absence or deficiency (<40% of normal mean) GAA activity (AANEM 2009), [documentation of a second GAA enzyme activity assay in a separate sample (from purified lymphocytes, fibroblasts, or muscle) or by GAA sequencing when results are indeterminate] OR  
    3. Molecular genetic testing for deletion or mutations in GAA gene (documentation must be submitted) AND
    4. Documentation of baseline percent predicted FVC and 6MWT (In adolescents and adults). AND  
    5. Prescribed by, or in consultation with, a neurologist or specialist in Pompe disease AND
    6. Will not be used concomitantly with other enzyme replacement therapies, (i.e., avalglucosidase alfa) AND
    7. Must be dosed in accordance with the FDA label.
 
Continuation of therapy – no more than 12 months
    1. Member has experienced a positive clinical response to therapy (improved respiratory/cardiac function, improved endurance, etc.)
    2. Dosed in accordance with FDA labeling
    3. Will not be used concomitantly with other enzyme replacement therapies, (i.e., avalglucosidase alfa).  
 
Dosage and Administration
Dosing per FDA Guidelines
 
The recommended dose of Alglucosidase alfa is 20mg/kg administered once every two weeks as an intravenous infusion.
 
Alglucosidase alfa is available as a 50mg powder in a single-dose vial for reconstitution.
 
Alglucosidase alfa should be administered by a healthcare professional.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Alglucosidase alfa does for any indication or circumstance not described above, not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
 
For members with contracts without primary coverage criteria, the use of Alglucosidase alfa in any other condition than listed above is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective March 11, 2021 - February 23, 2020
 
Effective March 11, 2021, Prior Approval is required for Alglucosidase alfa.
 
The initial use of this drug requires documentation of direct physician involvement and signature in the ordering and evaluation as documented in the medical records submitted for prior approval. Concurrent review will require continued evidence of appropriate physician involvement.  
 
Meets Primary Coverage Criteria or Is Covered for Contracts Without Primary Coverage Criteria
 
The use of Alglucosidase alfa meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for Pompe disease when dosed in accordance with FDA labeling and the following criteria are met:
 
Initial Approval (6 months)
 
Infantile-onset (ACMG, 2017)
    1. Member has an absence or deficiency (<1% of normal mean) GAA activity in skin fibroblasts OR biallelic deletion or mutation in GAA gene (documentation must be submitted) AND
    2. Member is experiencing disease symptoms (respiratory and/or skeletal muscle weakness) OR
    3. Member has confirmed evidence of cardiac hypertrophy AND
    4. Prescribed by, or in consultation with, a neurologist or specialist in Pompe disease
 
Non infantile-onset (ACMG, 2014)
    1. Member has an absence or deficiency (<40% of normal mean) GAA activity in lymphocytes, fibroblasts or muscle OR deletion or mutation in GAA gene (documentation must be submitted) AND
    2. Member has ability to walk 40 meters on the 6-minute walk test (assistive devices permitted) AND
    3. Member’s forced vital capacity (FVC) is 30 - 80% of predicted value AND
    4. Member has evidence of muscle weakness in the lower extremities AND
    5. Prescribed by, or in consultation with, a neurologist or specialist in Pompe disease
 
Continuation of therapy
    1. Member has experienced a positive clinical response to therapy (improved respiratory/cardiac function, improved endurance, etc.)
    2. Dosed in accordance with FDA labeling
 
Dosage and Administration
 
The recommended dose of Alglucosidase alfa is 20mg/kg administered once every two weeks as an intravenous infusion.
 
Alglucosidase alfa is available as a 50mg powder in a single-dose vial for reconstitution.
 
Alglucosidase alfa should be administered by a healthcare professional.
 
Please refer to a separate policy on Site of Care or Site of Service Review policy #2018030 for pharmacologic/biologic medications.
 
 
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
 
Alglucosidase alfa does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for any other indication.
 
For members with contracts without primary coverage criteria, the use of Alglucosidase alfa in any other condition than listed above is considered investigational.
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Rationale:
The safety and efficacy of alglucosidase alfa in infantile-onset Pompe Disease was evaluated in 3 separate clinical trials. Study 1 was an international, multicenter, open-label trial. 18 infants were enrolled to receive either 20mg/kg or 40mg/kg alglucosidase alfa once every two weeks with the length of treatment ranging from 52 to 106 weeks. Inclusion criteria included patients 7 months of age or younger at first infusion, clinical signs of Pompe disease, and cardiac hypertrophy. Patients were not eligible for the study if they required ventilatory support. 14 patients were cross reactive immunologic material (CRIM) positive and 4 patients were CRIM-negative. Efficacy was assessed comparing alglucosidase alfa treated patients at 18 months of age with a historical cohort of untreated infantile-onset Pompe disease patients with similar age and disease severity. 61 untreated patients with infantile-onset Pompe disease and diagnosed by 6 months of age were identified by a retrospective review of medical charts. By 18 months of age, 15 of the 18 (83%) alglucosidase alfa treated patients were alive without invasive ventilatory support. 3 required invasive ventilator support. In the historical cohort only one of the 61 (2%) of patients were alive. No difference in outcome were observed between patients who received 20mg/kg versus 40mg/kg.
 
Study 2 was an international, multicenter, non-randomized, open-label clinical trial that enrolled 21 infantile-onset patients. Patients were 3 months to 3.5 years of age at first infusion. 18 patients were CRIM-positive and 3 were CRIM-negative. 5 patients were receiving invasive ventilatory support. Patients received 20mg/kg alglucosidase alfa every 2 weeks for up to 104 weeks. The primary outcome was the proportion of patients alive at 52 weeks. At 52 weeks, 16 of the 21 (76%) of patients were alive. Of the 16 patients free of invasive ventilatory support at study entry, 4 died, 2 required invasive ventilatory support, and 10 were free of invasive ventilatory support after 52 weeks of treatment. Of the 5 patients who were receiving invasive ventilatory support at study entry, 1 died, and 4 remained on invasive ventilatory support at Week 52.
 
Study 3 was an open-label, single-center trial that enrolled 18 infantile-onset Pompe disease patients who had a confirmed diagnosis of Pompe disease as identified through a newborn prescreening program. All patients were CRIM-positive. All patients were treated with alglucosidase alfa prior to 6 months of age. 16 of the 18 (88%) patients were alive at 18 months of age and all were alive without invasive ventilator support.
 
The safety and efficacy of alglucosidase alfa in late-onset Pompe disease was assessed in 90 patients aged 10 to 70 years, in a randomized, double-blind, placebo-controlled trial. All patients were naïve to enzyme replacement therapy. 60 patients received 20mg/kg alglucosidase alfa and 30 patients received placebo every other week for 78 weeks. Upon study entry, all patients were ambulatory, did not require invasive ventilatory support or non-invasive ventilation while awake and sitting upright, and had a forced vital capacity (FVC) between 30-79% of predicted in the sitting position. 81 patients completed the trial. At study entry, the mean % predicted FVC in the sitting position in all patients was about 55%. After 78 weeks, this increased to 56.2% for alglucosidase alfa treated patients and decreased to 52.8% for placebo treated patients. At study entry, the mean 6 minute walk test in all patients was about 330 meters. After 78 weeks, the mean 6MWT increased by 25 meters for alglucosidase alfa-treated patients and decreased by 3 meters for placebo-treated patients. This indicates that alglucosidase alfa provides a 3.4% treatment effect in FVC and a 28 meter treatment effect in the 6 minute walk test. (Lumizyme, 2014)
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2021. No new literature was identified that would prompt a change in the coverage statement.
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2022. No new literature was identified that would prompt a change in the coverage statement.
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2022. No new literature was identified that would prompt a change in the coverage statement.
 
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2023. No new literature was identified that would prompt a change in the coverage statement.
CPT/HCPCS:
96365Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); initial, up to 1 hour
96366Intravenous infusion, for therapy, prophylaxis, or diagnosis (specify substance or drug); each additional hour (List separately in addition to code for primary procedure)
J0221Injection, alglucosidase alfa, (lumizyme), 10 mg
References: American College of Medical Genetics (ACMG) Work Group on Management of Pompe Disease.(2006) Pompe disease diagnosis and management guideline. Genetics in Med. 2006; 8(5):267-288.

Van der Ploeg AT, Clemens PR, Corzo D, et al.(2010) A Randomized Study of Alglucosidase Alfa in Late-Onset Pompe’s Disease. The New England Journal of Medicine. 2010;362:1396-406.

Van Gelder CM, Poelman E, Plug I, et al.(2016) Effects of a higher dose of alglucosidase alfa on ventilator-free survival and motor outcome in classic infantile Pompe disease an open-label single-center study. J Inherit Metab Dis. 2016; 39:383-390.

. Lumizyme [Package insert], Cambridge, MA. Genzyme Corporation; 2014.

Culper EJ, Berger KI, Leshner RT, et al.(2011) Consensus Treatment Recommendations for Late-Onset Pompe Disease. American Association of Neuromuscular & Electrodiagnostic Medicine. 2011
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants or to the Tyson Group Health Plan participants.
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