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Pompe Disease

Pompe disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called acid α-glucosidase (GAA). Reduced or absent levels of GAA lead to the accumulation of the substrate glycogen in the lysosomes of muscles and other tissues. Progressive accumulation of glycogen is believed to lead to the symptoms of Pompe disease, including muscle weakness and respiratory insufficiency. ERT with recombinant human GAA (rhGAA, Myzoyme®/Lumizyme®) are the first and only treatments approved for Pompe disease. However, ERT is not a cure and has several potential limitations, including the occurrence of immune responses in a majority of Pompe patients receiving rhGAA infusions.1 For more information about Pompe disease, please click here.

Amicus is leveraging its Chaperone-Advanced Replacement Therapy (CHART™) platform in combination with a uniquely-engineered, proprietary rhGAA (designated AT-B200) to develop a next-generation ERT for Pompe disease. AT-B200 has significantly higher amounts of mannose 6-phosphate (M6P) carbohydrates which may enable better drug targeting than existing Pompe ERTs. In preclinical studies, AT-B200 was shown to have superior uptake and activity in disease-relevant tissues that correlated with clearance of accumulated glycogen substrate when compared to current standard of care. AT-B200 may be further improved through the application of the Company’s proprietary conjugation technology to attach vIGF2 (a variant of the insulin growth factor 2 receptor) to further enhance drug targeting. The vIGF2 peptide binds the intended IGF2 receptor, but does not bind to insulin or the IGF1 receptor.

Co-formulating AT-B200 with the pharmacological chaperone AT2220 (duvoglustat HCl) may also deliver benefits. In preclinical studies of AT2220 co-administered3 and co-formulated4 with Myozyme/Lumizyme, greater enzyme uptake in disease-relevant tissues led to greater glycogen reduction compared to either of these ERTs alone. Taken together these results support the further investigation of a next-generation ERT that combines AT-B200 with a pharmacological chaperone for Pompe disease.

Development Status
Amicus is currently conducting preclinical studies to assess AT-B200 in combination with AT2220. Initial human proof-of-concept for the chaperone-ERT combination approach in Pompe disease was established in a Phase 2 study (Study 010). The results from this study demonstrated that co-administration of oral AT2220 just prior to infusing Myozyme/Lumizyme increased GAA enzyme activity in muscle tissue compared to these ERTs alone.2


1. Lacana E, et al., Am J Med Genet C Semin Med Genet. 2012 160C:30-39

2. Kishnani P, et al.,LDN WORLD 2013

3. Khanna R, et al., PLoS ONE (2012) 7(7): e40776. doi:10.1371/journal.pone.0040776.

4. Khanna R, et al., LDN WORLD 2013


Pompe disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called acid α-glucosidase (GAA) that leads to progressive muscle weakness and respiratory insufficiency.

To learn more about Pompe disease, click here.

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