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).

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)

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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)

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

Cipaglucosidase alfa (Pombiliti)

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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.

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)

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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).

Follow-up

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Media Gallery

Glycogen-storage disease type II (Pompe disease). Photomicrograph of the liver. Note the intensively stained vacuoles in the hepatocytes (periodic acid-Schiff, original magnification X 27).
Glycogen-storage disease type II (Pompe disease). Photomicrograph of the liver. Note the regular reticular net and hepatocytes vacuolization (Gordon-Sweet stain, original magnification X 25).

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Author

Germaine L Defendi, MD, MS, FAAP Associate Clinical Professor, Department of Pediatrics, Olive View-UCLA Medical Center

Germaine L Defendi, MD, MS, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lois J Starr, MD, FAAP Assistant Professor of Pediatrics, Clinical Geneticist, Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center

Lois J Starr, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Edward Kaye, MD Vice President of Clinical Research, Genzyme Corporation

Edward Kaye, MD is a member of the following medical societies: American Academy of Neurology, Society for Inherited Metabolic Disorders, American Society of Gene and Cell Therapy, American Society of Human Genetics, Child Neurology Society

Disclosure: Received salary from Genzyme Corporation for management position.

Margaret M McGovern, MD, PhD Professor and Chair of Pediatrics, Stony Brook University School of Medicine

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Acknowledgements

Jennifer Ibrahim, MD Chief, Genetics Division, St Joseph's Children's Hospital

Jennifer Ibrahim, MD is a member of the following medical societies: American Society of Human Genetics

Disclosure: Nothing to disclose.

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

Medication Summary

Enzyme replacement