Coverage Policy Manual
Policy #: 2021041
Category: Pharmacy
Initiated: November 2021
Last Review: December 2025
  Avalglucosidase alfa-ngpt (e.g., Nexviazyme)
Description:
This policy applies to the following medications: Avalglucosidase alfa (e.g., Nexviazyme).
Policy/
Coverage:
Prior Approval is required for avalglucosidase alfa (e.g., Nexviazyme).
 
INITIAL AND CONTINUATION APPROVAL will be for duration of the treatment course or 12 months (whichever comes first). Approval timeframes may differ for members/participants of Self-Insured plans.
 
Effective February 19, 2026
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Avalglucosidase alfa (e.g., Nexviazyme) meets member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes or for members with contracts without Primary Coverage Criteria, is considered Medically Necessary and is covered when the following criteria are met:
 
Initial Approval and Continuation of Therapy:
 
Member receives a “recommended” determination from InterQual® Criteria review for Avalglucosidase alfa (e.g., Nexviazyme), based on diagnosis and requested product. Click here to view the InterQual® criteria.
 
Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria
 
Avalglucosidase alfa (e.g., Nexviazyme) does not meet member benefit certificate Primary Coverage Criteria that there be scientific evidence of effectiveness in improving health outcomes and is not covered for any indication or circumstance not described above.
 
For contracts without Primary Coverage Criteria, Avalglucosidase alfa (e.g., Nexviazyme) is considered not Medically Necessary and is not covered or is investigational for any indication or circumstance not described above. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Please refer to a separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
 
Please refer to a separate policy on Maximum Dosage and Frequency (policy #2025031) for pharmacologic/biologic medications.
 
Effective December 19, 2023 to February 18, 2025
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of avalglucosidase alfa intravenous infusion meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes for patients with late-onset Pompe disease when ALL the following criteria are met:  
 
INITIAL APPROVAL STANDARD REVIEW for up to 12 months
 
Late Onset Pompe Disease (ACMG, 2006, FDA label 2021; Hani, 2021)
 
1. Individual is > 1 years of age; AND
2. 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/OR
b. Genetic testing showing a mutation in the GAA gene (documentation must be submitted); AND
3. 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
4. Prescribed by, or in consultation with, a neurologist or specialist in Pompe disease; AND
5. Will not be used:
a. Concomitantly with alglucosidase alfa or cipaglucosidase alfa-atga) or had a previous failure of alglucosidase alfa; OR  
b. In an individual with Pompe specific cardiac hypertrophy; OR
c. In an individual that requires invasive ventilation; OR
d. In an individual that has a percent predicted FVC of < 30% or > 85%; AND
7. Must be dosed in accordance with the FDA label.
 
CONTINUED APPROVAL for up to 1 year
 
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 in combination with other enzyme replacement therapies (e.g., alglucosidase-alfa or cipaglucosidase alfa-atga)
 
Dosing and administration
Dosing per FDA Guidelines
 
See the full prescribing information for dosage modifications (due to hypersensitivity reactions or IARs) and IV infusion volumes.  For individuals weighing:
1. > 30 kg, the recommended dosage is 20 mg/kg (of actual body weight) every two weeks.
2. < 30 kg, the recommended dosage is 40 mg/kg (of actual body weight) every two weeks.    
 
Avalglucosidase alfa-ngpt is available as 100 mg lyophilized powder in a single-dose vial for reconstitution.
 
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
  
The use of avalglucosidase 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 avalglucosidase 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 December 2022 to December 18, 2023
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of avalglucosidase alfa intravenous infusion to treat patients 1 year and older meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for patients with late-onset Pompe disease and they meet ALL the following criteria:  
 
Initial Approval (6 months) Late onset (ACMG, 2006, FDA label 2021; Hani, 2021)
 
    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
    6. Will not be used concomitantly with alglucosidase alfa or had a previous failure of alglucosidase alfa.  
 
Continuation of therapy – no more than 12 months
 
    1. Member has experienced a positive clinical response to therapy as evidenced by an improvement or stabilization in percent predicted FVC and/ or 6MWT.
    2. Dosed in accordance with FDA labeling
    3. Will not be used in combination with other enzyme replacement therapies (i.e., alglucosidase-alfa)
 
Dosing and administration
 
See the full prescribing information for dosage modifications (due to hypersensitivity reactions or IARs) and IV infusion volumes.  For patients weighing:
    1. >30 kg, the recommended dosage is 20 mg/kg (of actual body weight) every two weeks.
    2. <30 kg, the recommended dosage is 40 mg/kg (of actual body weight) every two weeks.   
 
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
  
The use of avalglucosidase alfa does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for any indication or any circumstance other than those outlined above including:
 
    1. The patient has Pompe specific cardiac hypertrophy.
    2. Requires invasive ventilation
    3. Has a percent predicted FVC of <30% or >85%
 
For members with contracts without primary coverage criteria, the use of avalglucosidase alfa (Nexviazyme) for any indication or circumstance other those outlined above are considered investigational including:
 
    1. The patient has Pompe specific cardiac hypertrophy.
    2. Requires invasive ventilation
    3. Has a percent predicted FVC of <30% or >85%
 
Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective November 24, 2021 to November 2022
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
The use of avalglucosidase alfa intravenous infusion to treat patients 1 year and older meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for patients with late-onset Pompe disease and they meet ALL the following criteria:  
 
Initial Approval (6 months) Late onset (ACMG, 2006, FDA label 2021; Hani, 2021)
 
    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
    6. Will not be used concomitantly with alglucosidase alfa or had a previous failure of alglucosidase alfa.  
 
Continuation of therapy – no more than 12 months
 
    1. Member has experienced a positive clinical response to therapy as evidenced by an improvement or stabilization in percent predicted FVC and/ or 6MWT.
    2. Dosed in accordance with FDA labeling
    3. Will not be used in combination with other enzyme replacement therapies (i.e., alglucosidase-alfa)
 
Dosing and administration
 
See the full prescribing information for dosage modifications (due to hypersensitivity reactions or IARs) and IV infusion volumes.  For patients weighing:
    1. >30 kg, the recommended dosage is 20 mg/kg (of actual body weight) every two weeks.
    2. <30 kg, the recommended dosage is 40 mg/kg (of actual body weight) every two weeks.   
 
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
  
The use of avalglucosidase alfa does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness for any indication or any circumstance other than those outlined above including:
 
    1. The patient has Pompe specific cardiac hypertrophy.
    2. Requires invasive ventilation
    3. Has a percent predicted FVC of <30% or >85%
 
For members with contracts without primary coverage criteria, the use of avalglucosidase alfa (Nexviazyme) for any indication or circumstance other those outlined above are considered investigational.  Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Rationale:
InterQual® Criteria may be adopted in part and/or customized to reflect differences in interpretation of or new evidence found in the current published evidence from peer-reviewed, published literature in recognized medical journals from PubMed or as a result of the review of information from the Agency for Healthcare Research and Quality (AHRQ), the Cochrane Library, FDA Drug Prescribing Information, evidence-based national physician specialty societies and associations specialty society guidelines, National Institute of Health and Care Excellence (NICE), appropriate government regulatory bodies including state and federal laws, input from external clinical experts and other evidentiary sources.
 
The approval of avalglucosidase alfa (Nexviazyme) was based on the results of the Phase 3 COMET trial (Hani 2021), a 49-week randomized, double-blind, and multinational noninferiority study between avalglucosidase alfa (n=51) and alglucosidase alfa (n=49) in treatment-naïve patients with late-onset Pompe disease (LOPD).
 
The primary endpoint was to determine the effect of avalglucosidase alfa on respiratory muscle function, measured by upright forced vital capacity (FVC) % predicted.  Secondary endpoints included the effect of avalglucosidase alfa on functional endurance, inspiratory and expiratory muscle strength, upper and lower muscle strength, motor function and health related quality of life and safety.  
 
Treatment with avalglucosidase alfa resulted in greater improvements in upright FVC % predicted at all timepoints and a 2.43% greater increase in FEC %predicted compared to alglucosidase alfa at Week 49.  It also resulted in greater improvements in the 6-Minute Walk Test (6MWT) with 30.01-m and 4.71% greater increases, respectively.  The primary study objective, achieving statistical non-inferiority, was met (p=0.0074) and testing for superiority was borderline significant (p=0.0626). Treatment -emergent adverse events (AE) were reported in 86.3% of avalglucosidase alfa-treated and 91.8% of alglucosidase alfa-treated participants.  Serious AEs were reported in 8 avalglucosidase alfa-treated and 12 alglucosidase alfa-treated participants.  High titers and neutralizing antibodies were more prevalent for alglucosidase alfa.  (Hani, 2021)
 
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
In a phase 3 double-blind randomized clinical trial with crossover in the extension period patients 3 years and older with previously untreated late-onset Pompe disease (LOPD) were enrolled between November 2, 2016, and February 10, 2021, with primary analysis after 49 weeks. Patients were treated at 55 referral centers in 20 countries. Efficacy outcomes were assessed at 97 weeks and safety outcomes to last follow-up, with data cutoff on February 10, 2021. Data were analyzed from May to June 2021.
 
Random assignment (1:1) to receive 20 mg/kg of avalglucosidase alfa or alglucosidase alfa by intravenous infusion every other week for 49 weeks; thereafter, all patients received 20 mg/kg of avalglucosidase alfa every other week.
The primary outcome was the least squares (LS) mean change from baseline in FVC percent predicted. Secondary outcomes included the LS mean change from baseline in 6MWT, muscle strength, motor function, quality of life, and disease biomarkers. Safety and tolerability were also assessed.
 
Of 100 participants from the double-blind treatment period, 95 entered the extension period. Of these, 51 (54%) were men, and the mean (range) age was 48.3 (10-79) years. At the start of this study, mean upright FVC percent predicted was similar between treatment arms, and 6MWT distance was greater in the avalglucosidase alfa arm. From baseline to week 97, LS mean (SE) FVC percent predicted increased by 2.65 (1.05) for those who continued avalglucosidase alfa and 0.36 (1.12) for those who switched to avalglucosidase alfa. The LS mean (SE) 6MWT distance increased by 18.60 (12.01) m and 4.56 (12.44) m, respectively. For participants who switched to avalglucosidase alfa, FVC percent predicted remained stable (LS mean [SE] change from week 49 to 97, 0.09 [0.88]) and 6MWT distance improved (LS mean [SE] change from week 49 to 97, 5.33 [10.81] m). Potentially treatment-related adverse events were reported in 29 patients (56.9%) who continued avalglucosidase alfa and in 25 patients (56.8%) who switched.
 
In this randomized clinical trial extension, maintenance of positive clinical outcomes was demonstrated for patients continuing avalglucosidase alfa treatment. (Kishnani, 2023)
 
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through November 2024. No new literature was identified that would prompt a change in the coverage statement.
 
2025 Update
In the COMET trial, avalglucosidase alfa treatment for late-onset Pompe disease was safe, tolerable and associated with stabilization or improvement in disease parameters through 97 weeks. The trial was extended through 145 weeks of treatment.
 
In the phase 3, double-blind, randomized trial, participants with previously untreated late-onset Pompe disease were randomly assigned to receive 20 mg/kg avalglucosidase alfa or alglucosidase alfa every other week for 49 weeks; thereafter, all patients received 20 mg/kg avalglucosidase alfa every other week. For this analysis, efficacy was assessed at 145 weeks and safety to last follow-up (data cutoff: March 11, 2022).
 
Of 100 participants in the double-blind treatment period, 95 entered the open-label extension, and 88 completed ≥ 145 weeks of treatment. At study start, the mean upright FVC percent predicted was similar between treatment arms, and 6MWT distance was greater in the avalglucosidase alfa arm. From baseline to week 145, the LS mean (SE) FVC percent predicted increased by 1.38 (1.22) in the avalglucosidase alfa arm and 1.25 (1.34) in the switch arm. The LS mean (SE) 6MWT distance walked increased by 20.65 (9.60) m and 0.29 (10.42) m, respectively. Potentially treatment-related adverse events were reported in 27 patients (53%) in the avalglucosidase alfa arm and 25 patients (57%) in the switch arm. Anti-drug antibodies declined over time in both arms.
 
In the randomized clinical trial extension, positive clinical outcomes were maintained for patients taking avalglucosidase alfa for up to 145 weeks with no new safety concerns. (Kishnani, 2025)
CPT/HCPCS:
J0219Injection, avalglucosidase alfa-ngpt, 4 mg
References: American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM).(2021) Pompe. Available at: https://www.aanem.org/Patients/Disorders/Pompe. Accessed on July 19, 2021.

FDA Press Announcements:(2021) FDA Approves New Treatment for Pompe Disease. Last accessed 11/16/2021 https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-pompe-disease

Kishnani PS, Diaz-Manera J, Toscano A, et al.(2023) Efficacy and Safety of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease After 97 Weeks: A Phase 3 Randomized Clinical Trial.  JAMA Neurol. 2023;80(6):558–567. doi:10.1001/jamaneurol.2023.0552

Xu S, Lun Y, Frascella M, Garcia A, Soska R, Nair A, Ponery AS, Schilling A, Feng J, Tuske S, Valle MCD, Martina JA, Ralston E, Gotschall R, Valenzano KJ, Puertollano R, Do HV, Raben N, Khanna R:(2019) Improved efficacy of a next-generation ERT in murine Pompe disease. JCI Insight. 2019 Mar 7;4(5). pii: 125358. doi: 10.1172/jci.insight.125358. eCollection 2019 Mar 7.
Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants.
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