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Pompe Disease (AT2220)
Amicus is leveraging its Chaperone-Advanced Replacement Therapy (CHART™) platform to develop the small molecule pharmacological chaperone
AT2220 (duvoglostat HCl) in combination
with ERT for 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 α-glucosidase (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
AT2220 is designed to bind to the rhGAA enzyme, stabilizing the enzyme in its properly folded and active form. Positive
results from a Phase 2 study (Study 010) established human proof-of-concept that co-administration of oral AT2220 just
prior to infusing Myozyme/Lumizyme increases GAA enzyme activity in muscle tissue compared to these ERTs alone.2 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. Preclinical results to date
also suggest that AT2220 in combination with ERT may mitigate ERT-induced immunogenicity by stabilizing the enzyme in
its properly folded and active form.
Amicus is developing a novel intravenous formulation of AT2220 (AT2220-IV) co-administered with ERT in Phase 2 for individuals with Pompe disease. When co-administered with ERT, AT2220-IV is designed to have an improved pharmacokinetic (PK) profile compared to oral AT2220 for all Pompe patients, many of whom are unable to swallow an oral small molecule (capsule).
In addition, an investigational next-generation ERT (AT2220 co-formulated with a proprietary rhGAA enzyme) is in preclinical studies to improve the properties of the rhGAA enzyme itself while incorporating AT2220 as a small molecule stabilizer. Successful development of a more stable ERT may also enable more convenient delivery of next-generation ERTs.
The U.S. Food and Drug Administration's Office of Orphan Products Development has
granted orphan drug designation for the active ingredient in AT2220 in the United
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.