Amicus Therapeutics Highlights Data Featured at Lysosomal Disease Network
WORLD Symposium 2014
First Scientific Meeting to Present Preclinical Proof-of-Concept Data for
Next-Generation Pompe ERT and Proprietary Enzyme Targeting Technology
Encouraging Additional Post-Hoc Analyses of Interim Data from Phase 3 Fabry
Monotherapy Study 011
CRANBURY, N.J., Feb. 12, 2014 (GLOBE NEWSWIRE) -- Amicus Therapeutics
(Nasdaq:FOLD), a biopharmaceutical company at the forefront of therapies for
rare and orphan diseases, today summarized the key highlights from 2 oral
platform presentations featuring its Pompe and Fabry programs at the Lysosomal
Disease Network WORLD Symposium (LDN WORLD) 2014. LDN WORLD is taking place in
San Diego, CA from February 10-13, 2014.
John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics,
Inc., stated, "At this year's WORLD Symposium we are highlighting data from
several of our ongoing development programs. This is the first scientific
meeting to feature our next-generation Pompe ERT and proprietary enzyme
targeting technology, purchased through our acquisition of Callidus Biopharma.
Together with our Chaperone-Advanced Replacement Therapy, or CHART, platform
these technologies may provide a unique tool set to address some of the major
challenges with currently marketed ERT products – enzyme activity and
stability; targeting and uptake; and tolerability and immunogenicity. We are
also pleased to present further, post-hoc analyses of 6-month data from our
first of two ongoing Phase 3 Fabry monotherapy studies, which we believe
demonstrate that migalastat HCl is having a positive impact in Fabry patients
with amenable mutations."
Preclinical Proof-of-Concept Data for Next-Generation Pompe ERT and
Proprietary Enzyme Targeting Technology
Preclinical proof-of-concept data for AT-B200, Amicus' proprietary recombinant
human acid-alpha glucosidase (rhGAA) for Pompe disease, as well as an overview
of the Company's proprietary peptide tagging technology (vIGF-2), will be
presented to a scientific audience for the first time at LDN WORLD 2014.
AT-B200 is differentiated from other Pompe ERTs by its unique carbohydrate
structure. This ERT may be further optimized through co-formulation with
Amicus' pharmacological chaperone AT2220 to improve enzyme stability and
tolerability, and by applying the Company's peptide tagging technology for
better targeting. Preclinical results have shown that AT-B200 and AT-B200
conjugated with vIGF-2 ("tagged AT-B200") were better than Lumizyme for
clearing glycogen in skeletal muscles in GAA knock-out mice after 4 weekly IV
Hung Do, PhD, Senior Vice President, Amicus Therapeutics, Inc., stated, "After
spending over a decade developing enzyme replacement therapies for Pompe and
other lysosomal storage diseases at Genzyme and Novazyme, AT-B200 was
developed to be a next-generation Pompe ERT with a unique carbohydrate
structure that may better target skeletal muscles. Our preclinical studies to
date demonstrate the potential for AT-B200 in Pompe disease, as well as the
differences between our peptide tagging technology and other IGF-2 tagging
approaches in development. We look forward to further preclinical development
to evaluate tissue uptake and glycogen clearance with longer dosing schedules
of AT-B200, with and without a pharmacological chaperone."
Updated 6-Month Data from Fabry Monotherapy Phase 3 Study 011
Study 011 6-Month (Stage 1) Data Migalastat Group Placebo Group P-Value
Primary Endpoint: Responder Analysis (≥
50% Reduction in Interstitial Capillary 41% 28% 0.300
GL-3) (ITT; n = 64; 32 per group)^1
Post-Hoc Analysis: Mean Change in -0.22 ± 0.11 +0.06 ± 0.09 0.052
Inclusions Per Capillary*
(mITT; n = 60; 30 per group)^2
Post-Hoc Analysis: Mean Change in
Inclusions Per Capillary* in GLP HEK
Amenable Patients (n = 46; 25 in -0.31 ± 0.12 +0.10 ± 0.13 0.002
migalastat HCl group, 21 in placebo
^1ITT = patients with evaluable baseline kidney biopsies; patients with
unevaluable 6-month biopsies counted as non-responders.
^2mITT = patients with evaluable paired biopsies (baseline and month 6)
^3GLP HEK Amenable = patients with amenable mutations in GLP-validated HEK
*ANCOVA model with covariate adjustment for baseline value and
Migalastat HCl monotherapy is being investigated in two ongoing Phase 3
studies (Study 011 and Study 012) in Fabry patients with amenable mutations.
Study 011 enrolled a total of 67 patients to compare migalastat HCl to placebo
in reducing kidney interstitial capillary globotriaosylceramide (GL-3).
Top-line data from the 6-month double-blind, placebo-controlled treatment
period (Stage 1) in Study 011 was previously reported. Updated Stage 1 data,
including a post-hoc analysis of the mean change from baseline in inclusions
per capillary as a continuous variable ("mean change in GL-3"), are being
presented at LDN WORLD^2.
Raphael Schiffmann, M.D., M.H.Sc., Medical Director of the Institute of
Metabolic Disease, Baylor Research Institute, stated, "As an investigator
working on the development of migalastat HCl and other new treatments for
patients living with Fabry disease, I was very encouraged to see the post-hoc
analysis of Stage 1 data from Study 011. These data clearly show that
migalastat HCl has a biological effect in Fabry patients with amenable
mutations. We look forward to seeing the 12- and 24-month data from this study
later this year."
The primary endpoint in Study 011 analyzed the percent change in kidney
interstitial capillary GL-3 inclusions from baseline to month 6 (responder
analysis with a 50% reduction threshold). However, the variability and low
levels of GL-3 at baseline contributed to a higher-than-anticipated placebo
response. Following the unblinding of the Stage 1 data, and while still
blinded to the Stage 2 data, Amicus identified a more appropriate way to
control for the variability in GL-3 levels in Study 011. A post-hoc analysis
of the mean change in GL-3 was deemed appropriate to measure the biological
effect of migalastat HCl.
Amicus plans to analyze the mean change in GL-3 at 12 months (Stage 2) in the
modified-intent-to treat population as well as a subgroup of patients with
amenable mutations in a GLP-validated human embryonic kidney (HEK) cell-based
in vitro assay ("GLP HEK assay"). The Stage 2 results and complete data from
the 24-month study, including clinical outcome measures such as eGFR and
proteinuria, are expected during the second quarter of 2014. Amicus remains
blinded to the 12- and 24-month data at this time. Top-line data is
anticipated in the second half of 2014 from the second Phase 3 study, or Study
012, which is comparing migalastat HCl to current standard of care ERTs.
About Study 011
Study 011 is a 24-month study consisting of a 6-month double-blind,
placebo-controlled treatment period (Stage 1); a 6-month open-label follow-up
period (Stage 2); and a 12-month open-label extension phase. All patients
received migalastat HCl during Stage 2 and the open-label extension phase.
Change from baseline in kidney interstitial capillary GL-3 is being assessed
by histology in kidney biopsies at the end of Stage 1 and Stage 2.
Summary of Amicus Data Presentations and Posters at LDN WORLD
Amicus' development programs will be highlighted in a total of three oral
presentations and five posters at LDN WORLD. The poster sessions will be held
Tuesday, February 11 through Thursday, February 13, 2014 from 4:00 p.m. to
6:00 p.m. PT.
*Chemical Conjugation of Targeting Peptide to ERTs Improve Receptor Binding
and Substrate Clearance in Mouse Models of Disease – Hung Do, PhD
(presentation) and Russell Gotschall (poster), Amicus Therapeutics, Inc.
(Oral Presentation: Wednesday, February 12 at 2:45 p.m. PT)
*Subcutaneous Administration of Recombinant Human Acid Alpha-Glucosidase
Co-formulated with the Pharmacological Chaperone AT2220 Leads to Lysosomal
Uptake of rhGAA and Glycogen Reduction in Disease-relevant Tissues of
Pompe Mice – Yi Lun, Amicus Therapeutics, Inc.
*Strategy to Assess the Effect of Duvoglustat Co-administered with
Alglucosidase Alfa Infusion on the Immune Response to Enzyme Replacement
Therapy for Pompe Disease – Xiaoyang Wu, Amicus Therapeutics, Inc.
*Liquid Chromatography-Tandem Mass Spectrometry Determination of AT2220 in
Rodent Plasma and Tissues – Leo B. Dungan, Amicus Therapeutics, Inc.
*Phase 3 Study (FACETS) of Migalastat HCl for Fabry Disease: Post hoc GLA
Mutation-Based Identification of Subjects Likely to Show a Drug Effect –
Jeffrey P. Castelli, PhD (presentation) and Elfrida R. Benjamin (poster),
Amicus Therapeutics, Inc. (Oral Presentation: Thursday, February 13 at
11:15 a.m. PT)
*Glucosylceramide and Glucosylsphingosine Quantitation by Liquid
Chromatography-Tandem Mass Spectrometry to Enable Studies of Neuronopathic
Gaucher Disease – Rick Hamler, Amicus Therapeutics, Inc. (Oral
Presentation: Tuesday, February 11 at 10:30 a.m. PT)
About Amicus Therapeutics
Amicus Therapeutics (Nasdaq:FOLD) is a biopharmaceutical company at the
forefront of therapies for rare and orphan diseases. The Company is developing
novel, first-in-class treatments for a broad range of human genetic diseases,
with a focus on delivering new benefits to individuals with lysosomal storage
diseases. Amicus' lead programs include the small molecule pharmacological
chaperones migalastat HCl as a monotherapy and in combination with enzyme
replacement therapy (ERT) for Fabry disease; and AT2220 (duvoglustat HCl) in
combination with ERT for Pompe disease.
About Chaperone-Advanced Replacement Therapy (CHART)
The Chaperone-Advanced Replacement Therapy (CHART™) platform combines unique
pharmacological chaperones with enzyme replacement therapies (ERTs) for
lysosomal storage diseases (LSDs). In a chaperone-advanced replacement
therapy, a unique pharmacological chaperone is designed to bind to and
stabilize a specific therapeutic enzyme in its properly folded and active
form. This proposed CHART mechanism may allow for enhanced tissue uptake of
active enzyme, greater lysosomal activity, more reduction of substrate, and
lower immunogenicity compared to ERT alone. Improvements in enzyme stability
may also enable more convenient delivery of next-generation therapies. Amicus
is leveraging the CHART platform to develop proprietary next-generation
therapies that consist of lysosomal enzymes co-formulated with pharmacological
^1Do et al., LDN WORLD 2014
^2Castelli et al., LDN WORLD 2014
^3Dr. Schiffmann is an investigator in Amicus' clinical studies of migalastat
HCl, as well as a consultant and research collaborator of Amicus
This press release contains, and the accompanying conference call will
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statements are subject to other risks detailed in our Annual Report on Form
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hereof. This caution is made under the safe harbor provisions of Section 21E
of the Private Securities Litigation Reform Act of 1995.
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