Clinical UM Guideline

Subject:  Alglucosidase alfa (Lumizyme®, Myozyme®)
Guideline #:  CG-DRUG-28Current Effective Date:  10/06/2015
Status:ReviewedLast Review Date:  08/06/2015


This document addresses alglucosidase alfa products (Lumizyme and Myozyme [Genzyme Corporation, Cambridge, MA]) which are enzyme replacements used for specific indications as a treatment of Pompe disease.  Pompe disease (also known as acid maltase deficiency [AMD], glycogen storage disease type II [GSD II], glycogenosis type II), is a rare autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase (GAA), an enzyme that degrades lysosomal glycogen.  

Clinical Indications

Medically Necessary:

  1. Alglucosidase alfa (Lumizyme, Myozyme) are considered medically necessary for the treatment of individuals with infantile-onset Pompe disease when all of the following are met:
    1. Diagnosis of infantile-onset Pompe disease is confirmed with acid alpha-glucosidase deficiency (GAA) activity in skin fibroblasts of less than 1% of the normal mean or by GAA gene sequencing; and
    2. Presence of symptoms (for example respiratory and/or skeletal muscle weakness) of infantile-onset Pompe disease; and
    3. Evidence of hypertrophic cardiomyopathy.
  2. Alglucosidase alfa (Lumizyme) is considered medically necessary for the treatment of individuals with non-infantile onset (late-onset) Pompe disease when all of the following are met:
    1. Diagnosis of late-onset Pompe disease based on:
      1. GAA enzyme assay which shows reduced enzyme activity less than 40% of the lab specific normal mean value; and
      2. Confirmed by a second GAA enzyme activity assay in a separate sample (from purified lymphocytes, fibroblasts or muscle) or by GAA gene sequencing; and
    2. Forced vital capacity (FVC) 30 -79% of predicted value while in the sitting position; and
    3. Postural drop in FVC (in liters) of 10% or more from upright to supine position; and
    4. Ability to walk 40 meters on a 6-minute walk test (assistive devices permitted); and
    5. Muscle weakness in the lower extremities.

Not Medically Necessary: 

Alglucosidase alfa (Lumizyme, Myozyme) is considered not medically necessary when the criteria above are not met.

Alglucosidase alfa (Myozyme) is considered not medically necessary for the treatment of non-infantile onset (late-onset) Pompe disease.


The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member. 

J0220Injection, alglucosidase alfa, not otherwise specified, 10 mg [Myozyme]
J0221Injection, alglucosidase alfa, (Lumizyme), 10 mg
ICD-10 Diagnosis[For dates of service on or after 10/01/2015]
 All diagnoses
ICD-9 Diagnosis[For dates of service prior to 10/01/2015]
 All diagnoses
Discussion/General Information

Pompe disease was first described in 1932, but remained untreated until the first enzyme replacement therapy (ERT) became available in 2006.  Pompe disease is a result of a rare, autosomal recessive genetic defect leading to a deficiency of the lysosomal enzyme, GAA.  Clinical manifestations result from the accumulation of glycogen in various tissues and the spectrum of disease severity varies with respect to age of onset, rate of disease progression, and the extent of organ involvement (skeletal, respiratory, and cardiac).  Persistent accumulation of glycogen in the target tissues results in progressive debilitation, organ failure and/or death.  Estimates of the incidence vary, but approximately 1 in 40,000 births in the United States are affected by Pompe disease (Kishnani, 2006).

Currently, in the United States, Lumizyme and Myozyme are two marketed preparations of alglucosidase alfa ERTs for Pompe disease.  Both Lumizyme and Myozyme are human enzymes GAA encoded by the most predominant of the 9 observed haplotypes of this gene and produced by recombinant deoxyribonucleic acid (DNA) technology in a Chinese hamster ovary cell lines at two separate manufacturing sites.  Alglucosidase alfa enzyme replacements are administered as an intravenous infusion every 2 weeks and the dose is based on body weight.  According to the U.S. Food and Drug Administration (FDA) News Release in 2014, the products are now "chemically and biochemically comparable."

Clinically, Pompe disease, or GSDII, presents as a wide spectrum of phenotypes ranging from the severe rapidly progressive infantile-onset form to a more slowly progressive late-onset form (van der Ploeg, 2008).  The American College of Medical Genetics (ACMG) Work Group on Management of Pompe Disease (2006) considered Pompe disease a "continuum of disease spectrum varying by age of onset, organ involvement and degree of myopathy."  The ACMG has broadly classified Pompe disease as follows:

Infantile form 

Early or classic infantile-onset Pompe disease has rapid, progressive disease and is characterized by glycogen deposition in the heart, skeletal, and respiratory muscles resulting in severe hypertrophic cardiomyopathy, hepatomegaly, hypotonia, and respiratory failure, typically leading to death within the first year of life.  Generally, the activity of the GAA enzyme in the skin fibroblasts is less than 1% of normal controls.  The non-classic infantile-onset Pompe disease is a variant form that presents during the first year of life, but has slower progression and less severe cardiomyopathy.

Late-onset form 

Late-onset Pompe disease ([LOPD] also called childhood, juvenile, or muscular variant) is heterogeneous and usually presents later than infancy, although it can present at any age with progressive skeletal muscle weakness without cardiac involvement.  Individuals eventually develop respiratory failure and scoliosis from truncal weakness.  Typically, the proximal lower limb and paraspinal muscles are affected first, followed by involvement of the diaphragm and respiratory accessory muscles.  Generally, the activity of the GAA enzyme in skin fibroblasts ranges from 2% to 40% of normal controls.  The ACMG workgroup (2006) identified mild variant cases and juvenile-onset cases that "may present prior to 12 months of age."  The clinical presentation must be considered along with the age of onset when classifying cases.

The adult-onset form presents in the second to sixth decade of life and is characterized by progressive muscle weakness and loss of respiratory function, leading to early death (van der Ploeg, 2010).  Respiratory failure is typically the cause of significant morbidity and mortality.  The age of death varies depending on the rate of disease progression, comorbidities and the extent of respiratory muscle involvement.  Approximately 60% of individuals with LOPD have a mild reduction in vital capacity (less than 80% predicted) and 30–40% have moderate reduction (less than 60% predicted) (Kishnani, 2006).  Observational studies have shown mean annual declines in the percentage of predicted FVC in the range of 1.7% - 4.6% (van der Beek, 2009; Wokke, 2008).


Confirmatory diagnosis of infantile-onset versus LOPD is important due to the rapid progression of deterioration for those afflicted with the infantile-onset form.  Specialty consensus groups have published guidelines for the diagnosis and management of this rare disease.  The ACMG (2006) developed algorithms to diagnose and manage both types of Pompe disease.

There are various diagnostic testing methods for GAA enzyme activity to confirm Pompe Disease.  Blood-based assays utilizing a dried blood spot (DBS) from peripheral blood, purified lymphocytes or whole blood can be analyzed in a noninvasive and rapid manner.  The gold standard for quantitative GAA enzyme activity prior to the blood-based assays includes cultured fibroblasts and muscle biopsy samples.  Cultured fibroblast testing takes about 4 to 6 weeks to grow cultures from skin biopsy tissue.  Muscle biopsy is an invasive procedure, but GAA activity in muscle tissue can be measured rapidly.  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).

The AANEM's (2009) diagnostic criteria for LOPD noted:

Because diaphragm weakness often occurs early in the disease process and muscle weakness may not be evident until later in the disease course, respiratory evaluation is extremely important in patients who may have Pompe disease.  Neuromuscular clinics should encourage routine testing of FVC, first in the seated and then in the supine position; a 10% or greater fall in FVC after a change in position suggests diaphragm weakness and should raise the possibility of Pompe disease.

The AANEM consensus treatment recommendations for LOPD reported diaphragmatic weakness noted on measurement of FVC in seated and supine positions may precede any reduction in FVC while in the upright position.  Diaphragmatic weakness, "Is suggested if there is a greater than or equal to 10% decrease of FVC in the supine compared with the upright position; a greater than or equal to 30% decrease indicates severe weakness" (Cupler, 2012).

Alglucosidase Alfa Enzyme Replacement


In 2006, the FDA approved the biologics license application for alglucosidase alfa (Myozyme) to treat individuals with Pompe disease (GAA deficiency).  The 2014 FDA Product Information Label states:

Myozyme has been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease as compared to an untreated historical control, whereas use of Myozyme in patients with other forms of Pompe disease has not been adequately studied to assure safety and efficacy.  

An international, multicenter, open-label clinical trial of eligible children with infantile-onset Pompe disease treated with Myozyme compared clinical outcomes to 61 historical controls.  Eighteen enrolled children were randomized to either 20 mg/kg or 40 mg/kg of Myozyme every 2 weeks, with length of treatment ranging from 52 – 106 weeks.  Enrollment criteria included individuals with documented infantile-onset Pompe disease, including skin fibroblast GAA activity <1% of the normal mean and hypertrophic cardiomyopathy (left ventricular mass index greater than or equal to 65g/m2 by echocardiogram); and individuals were no older than 26 weeks at enrollment.  Exclusion criteria included respiratory insufficiency (oxygen saturation <90% or CO2 partial pressure >55 mmHg [venous] or >40mm Hg [arterial] on room air, any ventilator use), or any prior GAA treatment (Kishnani, 2007).

Efficacy was measured by comparing the number of Myozyme-treated individuals who died or needed invasive ventilator support with the mortality experienced by a historical cohort of individuals with untreated infantile-onset Pompe disease with similar age and disease severity.  By the age of 18 months, only 1 of the 61 historical controls was alive (98% mortality), indicating the poor outcome of individuals who are left untreated.  Within the first 12 months of treatment, 3 of 18 individuals treated with Myozyme required invasive ventilatory support (17%, with 95% confidence interval [CI] 4% to 41%); there were no deaths.  With continued treatment beyond 12 months, 4 additional individuals required invasive ventilatory support after receiving between 13 and 18 months of Myozyme treatment; 2 of these 4 individuals died after receiving 14 and 25 months of treatment, and after receiving 11 days and 7.5 months of invasive ventilatory support, respectively.  No other deaths have been reported through a median follow-up of 20 months, and all 16 surviving individuals continue to be followed.  Survival without invasive ventilatory support was substantially greater in the individuals treated with Myozyme in this study versus the expected poor survival of the historical controls.  Eleven of the 18 participants experienced 164 infusion-related reactions (i.e., rash, fever, urticaria, decreased oxygen saturation); ranging from mild to moderate intensity (Kishnani, 2007; Product Information Label, 2014).

Kishnani and colleagues (2009) reported results of an extension study of 16 children who continued to receive either 20 mg/kg or 40 mg/kg of alglucosidase alfa, biweekly, for up to a total of 3 years.  Survival rate for 17 of the 18 participants who reached age 24 months was 94.5% (95% CI, 83.9 to 100).  The survival rate at age 36 months was 72% (95% CI, 47.9 to 96).  Seven participants were censored from the analysis because although they were alive, the children had not reached age 36 months by the completion of the study.  In comparison, only 1 of the 61 untreated children in the historic control group survived to longer than 24 months (1.9%: 95% CI, 0-5.5).  The Kaplan-Meier invasive ventilation-free survival rates at age 24 months and 36 months were 66.7% (95% CI, 44.9 to 88.4) and 49.4% (95% CI, 26 to 72.8), respectively.  The authors noted treatment with alglucosidase alfa resulted in a reduction of death by 95%; risk of invasive ventilation or death by 91%, and risk of any type of ventilation or death by 87%.  The investigators also noted there were no differences in the dose-effects on survival or ventilator-free survival observed (Kishnani, 2009).

Strothette and colleagues (2010) reported 12-month results of a European trial in which 44 individuals with LOPD of various stages of severity were treated off-FDA label with alglucosidase alfa (Myozyme).  This open-label, multi-center, observational study involved treatment with 20mg/kg of Myozyme every other week.  Assessments were performed at baseline and every 3 months for the 12 months of ERT.  Assessments included serial measures of arm strength using the Walton Gardner Medwin scale (WGMS), and 4 timed function tests which consisted of a 10-m walk, 4-stair climb, modified Gowers' maneuver (rising by oneself from a supine to standing position), and a 6-min walk test with distance recorded.  Additional measures included manual muscle testing using the Medical Research Council (MRC) grading scale, forced vital capacity (FVC), creatine kinase (CK) levels and 36-Item Short Form (SF-36) assessments.  The authors noted that due to the heterogeneity of disease status, not all participants were able to complete all tests.  There were significant changes from baseline for the modified Gower's test (7.3 sec versus 6 sec), CK levels (mean decrease 10.5%) and the 6-min walk test (341 ± 149.5 m at baseline; 393 ± 157 m at endpoint; p=0.026) while there were no changes in the other functional measures.  Although CK levels decreased significantly, they did not correlate to disease severity or results in functional tests.  The investigators noted the open-label trial design without a control group could "Neither prove nor disprove that ERT with alglucosidase alfa (Myozyme) is an effective treatment, but concluded that the results suggested ERT resulted in stabilization of neuromuscular deficits over one year with mild functional improvement." 

Black Box Warning – Myozyme
The Product Information Label (2014) for Myozyme includes the following Black Box warnings:

Life threatening anaphylactic, severe, allergic and immune mediated reactions have been observed in some patients during Myozyme infusions. Therefore, appropriate medical support should be readily available when Myozyme is administered. 

Risk of Cardiorespiratory Failure
Individuals with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of their cardiac or respiratory compromise due to infusion reactions, and require additional monitoring.

Additional warnings and precautions from the FDA Product Information Label (2014) include:

Severe cutaneous and systemic immune mediated reactions: Monitor individuals for the development of systemic immune mediated reactions involving skin and other organs. 

Cardiac arrhythmias and sudden cardiac death during general anesthesia: Caution should be used when administering general anesthesia for the placement of a central venous catheter intended for Myozyme infusion.


In May 2010, the FDA approved alglucosidase alfa (Lumizyme) to treat individuals 8 years and older, with late (non-infantile) onset Pompe disease who do not have evidence of cardiac hypertrophy.  In August 2014, the FDA approved the expanded use of Lumizyme for individuals with late-onset (non-infantile) and infantile-onset forms of Pompe disease, including children less than 8 years of age (Product Information Label, 2014). 

The pivotal Late-Onset Treatment Study (LOTS) was a randomized, double-blind, placebo-controlled study with 90 participants with confirmed diagnosis of non-infantile onset Pompe disease.  Individuals meeting entry criteria were randomly assigned in a ratio of 2:1 to receive biweekly infusions of alglucosidase alfa (n=60, 20mg/kg) or placebo (n=30) for 78 weeks at 8 centers in the United States and Europe.  Trial participants who were unable to walk 40 meters in 6 minutes, or were unable to perform appropriate pulmonary and muscle function testing were excluded.  Study entry was also limited to individuals who had a percentage of the predicted FVC within the range of 30% to less than 80% in the upright position, with a postural drop in FVC (in liters) of 10% or more (from upright to supine); and had evidence of muscle weakness in the lower extremities, defined as bilateral knee extension less than 80% of predicted performance, as measured by quantitative muscle testing (QMT).  Individuals were excluded if they required invasive ventilator support or required noninvasive ventilation while awake and upright.  The 2 primary end points used in the study were distance walked during a 6-minute walk test and percentage of predicted forced vital capacity (FVC).  At 78 weeks, the estimated mean changes from baseline in the primary end points favored alglucosidase alfa.  The alglucosidase alfa group had a mean increase of 25.1 m on the 6-minute walk test (6MWT, average baseline 332 m) while the placebo group had a decrease of 3.0 m (average baseline 318m) (p=0.03).  The estimated change in FVC as a percentage of each individual's predicted value was an increase of 1.2% for the treatment group and a decrease of 2.2% for the placebo group (p=0.006).  Subgroup analyses showed greater treatment effect between study groups with better baseline status.  A number of secondary measures were also reported including muscle testing (leg/arm), maximum inspiratory pressure, maximum expiratory pressure, and the SF-36 Physical Component Summary.  Of these secondary measures, only maximum expiratory pressure showed a significant difference between the treatment and placebo group.  Although the study group size is relatively large for such a rare disorder, the number is small when the outcomes are varied measures of disease progression.  The study does suggest that alglucosidase alfa treatment has a favorable, although modest, effect on walking distance and pulmonary function in individuals with LOPD and may stabilize proximal limb and respiratory muscle strength.  Anaphylactic, allergic, and infusion-associated reactions that involved urticaria, flushing, hyperhidrosis, chest discomfort, vomiting, and increased blood pressure occurred in 5% to 8% of the individuals treated with alglucosidase alfa but were not reported in the placebo group.  Of the 60 individuals in the alglucosidase alfa group, 3 (5%) had anaphylactic reactions, 2 of whom tested positive for IgE antibodies to alglucosidase alfa; 2 had respiratory and cutaneous reactions, and the third had severe tongue edema (van der Ploeg, 2010).

Black Box Warning - Lumizyme
The Product Information Label (2014) for Lumizyme includes the following Black Box warnings:

Life-threatening anaphylactic reactions and severe hypersensitivity reactions have occurred in some patients during and after alglucosidase alfa infusion.  Immune-mediated reactions presenting as proteinuria, nephrotic syndrome, and necrotizing skin lesions have occurred in some patients following alglucosidase alfa treatment.  Closely observe patients during and after alglucosidase alfa administration and be prepared to manage anaphylaxis and hypersensitivity reactions.

Infantile-onset Pompe disease patients with compromised cardiac or respiratory function may be at risk of serious acute exacerbation of their cardiac or respiratory compromise due to fluid overload, and require additional monitoring.

Additional warnings and precautions from the FDA Product Information Label (2014) include:

Risk of acute cardiorespiratory failure:  Individuals with compromised cardiac or respiratory function may be at risk of acute cardiorespiratory failure.  Caution should be exercised when administering alglucosidase alfa to patients susceptible to fluid volume overload.  Appropriate medical support and monitoring measures should be readily available.

Risk of cardiac arrhythmia and general anesthesia for central venous catheter placement:  Caution should be used when administering general anesthesia for the placement of a central venous catheter intended for alglucosidase infusion.

Monitoring laboratory tests:
Individuals should be monitored for IgG antibody formation every 3 months for 2 years and then annually thereafter.  Testing for IgG titers may also be considered if individuals develop hypersensitivity reactions or other immune mediated reactions or lose clinical response.  Individuals who experience anaphylactic or allergic reactions may also be tested for IgE antibodies to alglucosidase alfa and other mediators of anaphylaxis.

There are currently no marketed tests for antibodies against alglucosidase alfa, however a testing service is provided by Genzyme.

van der Ploeg and colleagues (2012) reported results from the open-label extension study following the pivotal LOTS trial.  From the initial 90 participants in the randomized controlled LOTS trial, those who completed Week 78 (55 individuals treated with alglucosidase alfa (Lumizyme) and 26 individuals crossed over from the control group) were enrolled into the LOTS extension study.  Participants were treated with biweekly IV infusions of alglucosidase 20mg/kg for up to an additional 26 weeks (to Week 104), and for those at sites within the United States, therapy could be continued for an additional 26 weeks (up to Week 130).  The 6MWT to measure functional endurance, and the percentage of predicted FVC in the upright position to measure respiratory muscle strength were the primary efficacy assessments.  Participants initially randomized to the alglucosidase arm had a LOTS baseline 6MWT of 332.2 ± 126.7 m. From baseline to Week 78, the mean increase in distance walked measured 28.2 ± 66.5 m, and from baseline to Week 104, an increase of 21.3 ± 78.0 m (95% CI = −0.2, 42.8).  The baseline percentage of predicted FVC in the upright position for the alglucosidase alfa treatment arm in LOTS was 55.4% ± 14.4%.  In the extension trial from LOTS baseline to Week 78, the mean change in percentage of predicted FVC was 1.3% ± 5.7% and from LOTS baseline to Week 104  a change of 0.8% ± 6.7% (95% CI = −1.1).  For the crossover group (placebo-to-active treatment), the mean distance walked in 6MWT prior to initiation of alglucosidase treatment at baseline of the extension study was 312.7 ± 147.2 m.  After 26 weeks of treatment, the mean increase in distance walked measured 4.2 ± 23.8 m (95% CI = −6.1, 14.5; n=23).  The percentage of predicted FVC in the upright position for the placebo arm at baseline for the extension treatment was 51.1% ± 15.8%.  After 26 weeks of treatment, the mean change in percentage of predicted FVC was −1.0% ± 5.4% (95% CI = −3.4).  There were no anaphylactic reactions and no deaths during the extension study.  Every participant had one AE reported, with the most frequently reported being falls (65%), headache (52%), and nasopharyngitis (48%).  Inhibitory antibodies by in vitro enzyme uptake assay had developed in 18 participants, but only 6 were positive at the last 2 time points.  The authors concluded the findings "indicate that the average patient treated with alglucosidase alfa for up to 104 weeks maintained the improved walking distance and stabilization in pulmonary function" initially observed in the first 78 weeks.  The investigators also noted the positive results for FVC at 78 weeks (1.3%) and 104 weeks (0.8%) contrast with the 2.2% decline in predicted FVC in the 78 week period for the placebo group in the pivotal LOTS trial.  The impact of antibodies on the safety and efficacy of alglucosidase alfa in individuals with LOPD requires further studies.

In a consensus statement for individuals with LOPD, ERT was not recommended for individuals who had no symptoms or objective signs (proximal muscle weakness or reduced FVC in either upright or supine position) of Pompe disease.  ERT was recommended for individuals with confirmed Pompe disease and demonstrable muscle weakness or reduction in pulmonary function.  The decision to continue ERT is complex and is individualized during routine neuromuscular clinic visits with the treating physician (Cupler, 2012).

A 3 year observational trial reported by Bembi (2010) evaluated the clinical outcome of alglucosidase alfa ERT in 24 patients (7 juveniles and 17 adults) with LOPD.  The results showed improvement in 6MWT and preservation of vital capacity and FEV1.  The pattern of responses in the juvenile participants demonstrated progressive improvement over 3 years of ERT, while the responses in adult participants reached and maintained a plateau after 12 months of therapy.  This uncontrolled observational study was limited to a small, heterogeneous group of individuals.  The authors noted further study is needed to determine if the treatment effect seen in this small trial can be generalized to a larger population.

In a retrospective study of 60 individuals who received 1 year or more of ERT treatment for LOPD, 6 participants (10%) developed high, sustained antibody titers (HSAT, ≥ 1:51,200).  From these, Patel (2012) described a series of three cases who had demonstrated significant clinical decline that was correlated with HSAT development.  The range of ERT duration was 68-255 weeks.  HSAT peak antibody titers ranged from 1:102,400 to 1:819,200 and neutralizing antibodies that inhibited enzyme uptake were demonstrated at least at 1 point.  The 3 LOPD participants initially demonstrated improvement or stabilization during the first 26-52 weeks of ERT therapy.  However, subsequent clinical decline demonstrated by pulmonary function, quality of life, and/or motor function testing corresponded with HSAT development.  The authors note despite the limitations of the study, these cases call for additional long-term studies to investigate the impact of HSAT on efficacy and safety of ERT for individuals with LOPD.  Additionally, antibody thresholds and adverse impact on treatment outcome need to be established.  Treatments such as immunomodulation protocols and selection criteria for appropriate high-risk individuals need to be studied in large groups with long-term follow-up.

Vianello and colleagues (2013) reported long-term results of 8 individuals with late-onset GSDII and treated with alglucosidase alfa ERT compared to 6 historical controls treated with home mechanical ventilation (HMV).  The primary efficacy endpoints were the number of pulmonary exacerbations resulting in hospitalization and the hours of daily HMV use.  Significantly lower annual rates of hospitalization were reported in the ERT group compared to the control group (0.42 [95% CI 0.2-0.76] vs. 0.96 [95% CI 0.62-1.42]).  Individuals treated with ERT also reported a significant reduction in the hours of HMV use on a daily basis from baseline to the end of the follow-up period, compared to individuals in the control group (-4.8 [95% CI -8.2-1.5] vs. -0.16 [95% CI -4.5 to 3.7] h; p=0.004).  The authors noted limitations of the study included the use of historical controls and the management of individuals on HMV has improved since the study period.  ERT in individuals with late-onset GSDII has demonstrated a reduction in dependency of ventilator use and the rate of hospitalization in this comparative study.  Ongoing research and support of the respiratory treatment of individuals with GSDII are continuing.

Alglucosidase alfa is being studied as a possible treatment approach for other indications such as glycogen storage disease type III (also known as GSDIII or Cori disease).  However, at this time, there is a paucity of published data from randomized controlled trials in humans to demonstrate the safety and efficacy of alglucosidase alfa to treat GSD III.


Cardiac hypertrophy: An abnormal enlargement of the heart muscle. 

Glycogen: Large branched polysaccharide consisting of glucose residues.  The major carbohydrate reserve of animals, stored primarily in liver and muscle, synthesized and degraded for energy as demanded. 

Medical Research Council's scale for grading muscle strength:
The individual's effort is graded on a scale of 0 to 5:

Vital capacity: The maximum amount expelled from the lungs after a maximum inspiration.


Peer Reviewed Publications: 

  1. Bembi B, Pisa FE, Confalonieri M, et al.  Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II.  J Inherit Metab Dis.  2010; 33(6):727-735.
  2. Case LE, Bjartmar C, Morgan, et al.  Safety and efficacy of alternative alglucosidase alfa regimens in Pompe disease.  Neuromuscul Disord.  2015; 25(4):321-332.
  3. de Vries JM, van der Beek NA, Hop WC, et al.  Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study.  Orphanet J Rare Dis. 2012; 7:73.
  4. Hundsberger T, Rösler KM, Findling O.  Cessation and resuming of alglucosidase alfa in Pompe disease: a retrospective analysis.  J Neurol.  2014; 261(9):1684-1690.
  5. Kishnani PS, Corzo D, Leslie ND, et al.  Early treatment with alglucosidase alpha prolongs long-term survival of infants with Pompe disease.  Pediatr Res.  2009; 66(3):329-335.
  6. 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.
  7. Kishnani PS, Nicolino M, Voit T, et al.  Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease.  J Pediatr.  2006; 49(1):89-97.
  8. Nicolino M, Byrne B, Wraith JE, et al.  Clinical outcomes after long-term treatment with alglucosidase alfa in infants and children with advanced Pompe disease.  Genet Med.  2009; 11(3):210-219.
  9. Orlikowski D, Pellegrini N, Prigent H, et al.  Recombinant human acid alpha-glucosidase (rhGAA) in adult patients with severe respiratory failure due to Pompe disease.  Neuromuscul Disord.  2011; 21(7):477-482.
  10. Patel TT, Banugaria SG, Case LE, et al.  The impact of antibodies in late-onset Pompe disease: a case series and literature review.  Mol Genet Metab.  2012; 106(3):301-309.
  11. Spiridigliozzi GA, Heller JH, Case LE, et al.  Early cognitive development in children with infantile Pompe disease.  Mol Genet Metab.  2012; 105(3):428-432.
  12. Strothotte S, Strigl-Pill N, Grunert B, et al.  Enzyme replacement therapy with alglucosidase alfa in 44 patients with late-onset glycogen storage disease type 2: 12-month results of an observational clinical trial.  J Neurol.  2010; 257(1):91-97.
  13. Toscano A, Schoser B.  Enzyme replacement therapy in late-onset Pompe disease: a systematic literature review.  J Neurol.  2013; 260(4):951-959.
  14. van der Beek N, Hagemans M, van der Ploeg A, et al.  Pompe disease (glycogen storage disease Type II): clinical features and enzyme replacement therapy.  Acta Neurol Belg.  2006; 106(2):82-86.
  15. van der Ploeg AT, Barohn R, Carlson L, et al.  Open-label extension study following the Late-Onset Treatment Study (LOTS) of alglucosidase alfa.  Mol Genet Metab. 2012; 107(3):456-461. 
  16. van der Ploeg AT, Clemens PR, Corzo D, et al.  A randomized study of alglucosidase alfa in late-onset Pompe's disease.  N Engl J Med.  2010; 362(15):1396-1406.
  17. van der Ploeg AT, Reuser AJ.  Pompe's disease.  Lancet.  2008; 372(9646):1342-1352.
  18. Vianello A, Semplicini C, Paladini L, et al.  Enzyme replacement therapy improves respiratory outcomes in patients with late-onset type II glycogenosis and high ventilator dependency.  Lung.  2013; 191(5):537-544.
  19. Wokke JH, Escolar DM, Pestronk A,  et al.  Clinical features of late-onset Pompe disease: a prospective cohort study.  Muscle Nerve.  2008; 38(4):1236-1245.

Government Agency, Medical Society, and Other Authoritative Publications: 

  1. Alglucosidase alfa.  In: DrugPoints® System (electronic version).  Truven Health Analytics, Greenwood Village, CO.  Updated May 14, 2015. Available at: Accessed on May 28, 2015.
  2. Alglucosidase Alfa Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised October 30, 2014. Accessed on May 28, 2015.
  3. American Association of Neuromuscular & Electrodiagnostic Medicine.  Diagnostic criteria for late-onset (childhood and adult) Pompe disease.  Muscle Nerve.  2009; 40(1):149-160.
  4. American College of Medical Genetics (ACMG) Work Group on Management of Pompe Disease.  Pompe disease diagnosis and management guideline.  Genetics in Med.  2006; 8(5):267-288.
  5. Cupler EJ, Berger KI, Leshner RT, et al.; AANEM Consensus Committee on Late-onset Pompe Disease.  Consensus treatment recommendations for late-onset Pompe disease.  Muscle Nerve.  2012; 45(3):319-333.
  6. Lumizyme [Product Information], Cambridge, MA. Genzyme Corporation; August 1, 2014.  Available at:  Accessed on May 28, 2015.
  7. Myozyme [Product Information], Cambridge, MA. Genzyme Corporation; May 20, 2014.  Available at:  Accessed on May 28, 2015.
  8. U.S. Food & Drug Administration.  FDA News Release. FDA expands approval of drug to treat Pompe disease to patients of all ages; removes risk mitigation strategy requirements. August 1, 2014. Available at:  Accessed on May 28, 2015.
Websites for Additional Information
  1. American College of Medical Genetics.  Available at:  Accessed on May 28, 2015.
  2. Lumizyme ACE Program.  Available at:  Accessed on May 28, 2015.
  3. National Institute of Neurological Disorders and Stroke.  Pompe Disease Information.  Last Updated February 20, 2013.  Available at:  Accessed on May 28, 2015.

Acid alpha-glucosidase (GAA) deficiency
Enzyme replacement therapy
Pompe disease

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.





Reviewed08/06/2015Medical Policy & Technology Assessment Committee (MPTAC) review. Updated Discussion, References and Websites sections. 
Revised08/14/2014Medical Policy & Technology Assessment Committee (MPTAC) review. Added Lumizyme to medically necessary criteria for infantile-onset Pompe disease. Remove age criterion from late-onset Pompe disease. Updated Discussion, Definitions, References and Websites. 
Revised08/08/2013MPTAC review. Added GAA gene sequencing into medically necessary diagnostic criteria for infantile Pompe Disease. Updated Discussion/General Information, References, and Website sections.
Revised05/09/2013MPTAC review.  Clarified medically necessary clinical indications.  Updated Discussion/General Information, References, and Website sections.
Reviewed11/08/2012MPTAC review. Updated Discussion, Definitions, References and Websites. 
Reviewed11/17/2011MPTAC review. Updated Discussion, References and Websites.  Updated Coding section with 01/01/2012 HCPCS changes; removed C9277 deleted 12/31/2011.
New11/18/2010MPTAC review. Initial document development.