Genetics of Glycogen-Storage Disease Type II (Pompe Disease) Medication

Updated: Oct 12, 2023
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
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Medication

Medication Summary

Several recombinant human enzymes alpha-glucosidase (rhGAA) have been approved by the FDA and are indicated for treatment of glycogen-storage disease type II (GSD II; Pompe disease).

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Enzyme replacement

Class Summary

Enzyme replacement therapy is approved in the United States and may ameliorate clinical symptoms. Enzyme replacement therapies are available for all age groups (ie, infantile [early onset] or late onset [juvenile/adult]) affected by Pompe disease. 

Replaces rhGAA, which is deficient or lacking in persons with Pompe disease. Alpha-glucosidase is essential for normal muscle development and function. It binds to mannose-6-phosphate receptors and then is transported into lysosomes, then undergoes proteolytic cleavage that results in increased enzymatic activity and ability to cleave glycogen. Infant survival is improved without requiring invasive ventilatory support compared with historical controls without treatment. 

Alglucosidase alfa (Lumizyme, Myozyme)

Myozyme has been shown to improve ventilator-free survival in patients with infantile-onset Pompe disease compared with untreated historical controls. It has not been adequately studied for treatment of other forms of Pompe disease. Lumizyme is indicated for infantile-onset Pompe disease and also for late (non-infantile) Pompe disease. 

Avalglucosidase alfa (Nexviazyme)

Indicated for treatment of patients aged 1 year and older with late-onset Pompe disease. 

Cipaglucosidase alfa (Pombiliti)

Indicated in combination with miglustat (Opfolda) for adults with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) who weigh ≥40 kg and are not improving on their current enzyme replacement therapy (ERT). 

Cipaglucosidase alfa is an rhGAA with optimized carbohydrate structures to enhance uptake into muscle cells. It is used with miglustat, which binds with, stabilizes, and reduces inactivation of cipaglucosidase alfa in blood.  

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Pharmacologic Chaperones

Class Summary

Miglustat binds with, stabilizes, and reduces inactivation of cipaglucosidase alfa in the blood after infusion. Bound miglustat is dissociated from cipaglucosidase alfa after it is internalized and transported into lysosomes. Miglustat alone has no pharmacological activity in cleaving glycogen. 

Miglustat (Opfolda)

Indicated in combination with cipaglucosidase alfa, a hydrolytic lysosomal glycogen-specific enzyme, for adults with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing ≥40 kg who are not improving on their current enzyme replacement therapy (ERT). 

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