Nexviazyme® (avalglucosidase alfa-ngpt) is manufactured by Sanofi Genzyme.1 ​​On August 6, 2021, the US Food and Drug Administration (FDA) approved Nexviazyme for the treatment of late-onset Pompe disease (LOPD) in patients aged 1 year and older. The approval is based on positive phase 3 data that demonstrated improvements in key disease burden measures and the establishment of the drug’s safety profile.

The drug is administered as an intravenous infusion.2 Nexviazyme targets the mannose-6-phosphate (M6P) receptor, which is the main pathway for enzyme replacement therapy (ERT), thus clearing up the buildup of glycogen in muscle cells.3

Pompe disease occurs due to a genetic deficiency or dysfunction of the lysosomal enzyme acid alpha-glucosidase (GAA), which leads to the buildup of glycogen in muscle cells. Glycogen accumulation results in irreversible muscle damage, including the diaphragm, which sustains the functions of the respiratory system and the skeletal muscles affecting endurance, mobility, and breathing. The essential pathway for transport of the GAA enzyme into the cell lysosomes is via the M6P receptor. Nexviazyme specifically targets M6P to enhance cellular enzyme uptake and improve the clearance of glycogen in target tissues.3 

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Myozyme® (alglucosidase alfa) was also developed by Sanofi Genzyme, and it obtained FDA approval in 2006 for infantile-onset Pompe disease.4 Lumizyme® ​​(alglucosidase alfa) is a lysosomal glycogen-specific enzyme administered in individuals aged 8 years and older with LOPD who show no evidence of cardiac hypertrophy. The safety and efficacy of Lumizyme have not been demonstrated in controlled clinical trials in patients with infantile-onset Pompe disease or LOPD (non-infantile) with onset before 8 years of age.5

Nexviazyme showed a 15-fold increase in M6P content compared to alglucosidase alfa, which was the comparator arm in a pivotal study.3

Mechanism of Action

GAA is required for the normal development of muscles and their functions. Carbohydrate groups on GAA molecules bind to M6P receptors, and GAA is then transported into the cell where it undergoes proteolytic cleavage, leading to increased enzymatic glycogen cleavage. The protein portion of Nexviazyme is metabolized into amino acids and small peptides by catabolic pathways. The half-life of Nexviazyme is 1.6 hr, and the clearance is 0.9 L/hr.6

Clinical Trial Results

The FDA decision to grant accelerated marketing approval to Nexviazyme is based on positive results from the phase 3 COMET trial (NCT02782741),7 whose conclusion is expected by September 2024, and the phase 2 mini-COMET trial (NCT03019406),8 expected to end in December 2024.4 Nexviazyme has shown improvements in individuals with LOPD. In the pivotal Phase 3 trial, COMET, Nexviazyme demonstrated improvements in walking distance measures and respiratory functions in patients with LOPD, and its safety profile was established.

Nexviazyme as a New ERT for LOPD

Nexviazyme helps to decrease glycogen accumulation.2 The administration involves monotherapy ERT every 2 weeks. The recommended dose is calculated based on body weight (20 mg/kg for LOPD cases ≥ 30 kg or 40 mg/kg for LOPD cases < 30 kg), and the drug is administered via an intravenous infusion. Nexviazyme is expected to become available in the US in the coming weeks.3

Warnings, Precautions, and Adverse Reactions

Severe hypersensitivity reactions such as anaphylaxis have been reported with Nexviazyme. The drug should be discontinued immediately in such cases and appropriate medical treatment should be made available. Desensitization can also be considered. 

In cases of severe infusion-associated reactions (IARs), immediate discontinuation is required. Milder reactions, however, can be managed by slowing down the infusion rate.

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Antipyretics, antihistamines, and/or corticosteroids can be administered before the infusions to reduce the risk of IARs. In some cases, rechallenge using slower infusion rates with a lower dose than the recommended dose has been done. The dose can be increased to the recommended approved dose when the patient starts to tolerate the infusion.

Acute cardiorespiratory failure risks have been observed in individuals susceptible to fluid overload and in those with underlying respiratory disease or compromised cardiac or respiratory functions. In such cases, vital signs should be monitored frequently.9

The most common adverse effects are fatigue, diarrhea, nausea, vomiting, headache, dizziness, pruritus, arthralgia, myalgia, dyspnea, erythema, paresthesia, and urticaria.2


  1. Avalglucosidase alfa (Rx): dosing & uses. Medscape. Accessed August 9, 2021.
  2. FDA approves new treatment for Pompe disease. US Food and Drug Administration. August 6, 2021. Accessed August 9, 2021.
  3. FDA approves Nexviazyme® (avalglucosidase alfa-ngpt), an important new treatment option for late-onset Pompe disease. Sanofi. August 6, 2021. Accessed August 9, 2021.
  4. Muscular Dystrophy Association celebrates FDA approval of (Nexviazyme) for treatment of Pompe disease. Muscular Dystrophy Association. August 6, 2021. Accessed August 9, 2021. 
  5. Lumizyme (alglucosidase alfa). Genzyme. Accessed August 9, 2021.
  6. Avalglucosidase alfa (Rx): pharmacology. Medscape. Accessed August 9, 2021.
  7. Study to compare the efficacy and safety of enzyme replacement therapies avalglucosidase alfa and alglucosidase alfa administered every other week in patients with late-onset Pompe disease who have not been previously treated for Pompe disease (COMET). May 25, 2016. Updated April 8, 2021. Accessed August 9, 2021.
  8. A study to assess safety and efficacy of avalglucosidase alfa administered every other week in pediatric patients with infantile-onset Pompe disease previously treated with alglucosidase alfa (mini-COMET). January 12, 2017. Updated October 1, 2020. Accessed August 9, 2021.
  9. Avalglucosidase alfa (Rx): warnings. Medscape. Accessed August 9, 2021.

Reviewed by Debjyoti Talukdar, MD, on 8/9/2021.