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Amicus
Therapeutics
today announced positive results from clinical and
preclinical studies of the pharmacological chaperone AT2220 (duvoglustat HCl)
in combination with ERT for Pompe disease at the Lysosomal Disease Network
WORLD Symposium (LDN WORLD).
John F. Crowley, Chairman and Chief Executive Officer of Amicus stated, "The
advancement of our core platform technology in Pompe and other lysosomal
storage disorders is a continued great step forward for Amicus. Across these
serious genetic diseases, we are leveraging this chaperone-ERT combination
platform to work towards improving currently marketed ERTs and to develop our
own proprietary next-generation ERTs that incorporate our small molecule
chaperones. These chaperone stabilizers have the potential to enhance ERT
activity and tissue uptake while also significantly reducing the
immunogenicity of the ERTs. Through these programs we hope to offer new
benefits and treatment options for patients with lysosomal storage diseases."
Chaperone-ERT Combinations for Pompe Disease
AT2220 Co-Administered with Marketed ERTs
Positive results from a Phase 2 study (Study 010) established human
proof-of-concept that co-administration of AT2220 just prior to infusing ERT
(Myozyme/Lumizyme, or rhGAA enzymes) increases GAA enzyme activity in muscle
tissue compared to ERT alone. These results appear in a poster^1 and will be
featured in an oral platform presentation at LDN WORLD on Friday, February 15
at 9:15 am ET.
Based on these results, Amicus plans to initiate a repeat-dose clinical study
in the third quarter of 2013 to evaluate a novel intravenous formulation of
AT2220 (AT2220-IV) co-administered with Myozyme/Lumizyme. AT2220-IV when
co-administered with ERT 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. The upcoming clinical study will
investigate multiple doses of AT2220-IV co-administered with Myozyme/Lumizyme
every two weeks in Pompe patients. Objectives of the study are to characterize
safety and PK for later evaluation of infants and special populations. Key
parameters are expected to include GAA enzyme activity and AT2220 levels in
plasma and muscle, as well as rhGAA antibody titers.
Next-Generation ERT (AT2220 Co-Formulated with a Proprietary Amicus ERT)
Preclinical studies of AT2220 co-formulated with rhGAA enzyme
(Myozyme/Lumizyme) were presented for the first time in a poster^2 at LDN
WORLD. This chaperone-ERT co-formulation resulted in up to 2.5-fold greater
enzyme uptake in multiple disease-relevant tissues and led to greater glycogen
reduction compared to rhGAA alone in GAA knock-out mice. Collectively these
data suggest that AT2220 directly binds to and stabilizes rhGAA, potentially
leading to a larger amount of properly folded, active enzyme available for
uptake into tissue. AT2220 co-formulated with ERT may also mitigate Pompe
ERT-related immunogenicity since properly-folded proteins are less prone to
aggregation and less immunogenic.
Following the completion of these preclinical studies, Amicus entered into a
contract with Laureate Pharmaceuticals for the manufacture of a proprietary
rhGAA enzyme. Amicus is developing AT2220 co-formulated with this proprietary
enzyme as a next-generation ERT for Pompe disease. Through this approach
Amicus believes it has the potential to improve the properties of the rhGAA
enzyme itself while incorporating AT2220 as a small molecule stabilizer to
increase exposure and tissue uptake, and reduce immunogenicity relative to
currently marketed ERTs. Successful development of a more stable ERT may also
enable novel routes of delivery such as subcutaneous administration.
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