Amicus Therapeutics Announces Additional Preliminary Results From Ongoing
Phase 2 Chaperone-Enzyme Replacement Therapy (ERT) Study for Fabry Disease
Drug-Drug Interaction Study Evaluating Pharmacokinetics and Safety Presented
CRANBURY, N.J., Nov. 8, 2012 (GLOBE NEWSWIRE) -- Amicus Therapeutics
(Nasdaq:FOLD), today announced additional preliminary results from an
open-label Phase 2 drug-drug interaction study (Study 013) to evaluate a
single oral dose of migalastat HCl (150 mg or 450 mg) co-administered with
enzyme replacement therapy (ERT) in males with Fabry disease. In a poster at
the American Society of Human Genetics (ASHG) Annual Meeting Dr. David G.
Warnock, University of Alabama-Birmingham, presented results from all 12
patients in the migalastat HCl 150 mg dose group.
Amicus, in collaboration with GlaxoSmithKline (GSK), is developing the
investigational pharmacological chaperone migalastat HCl as a monotherapy and
in combination with ERT for the treatment of Fabry disease. When
co-administered with ERT, migalastat HCl binds to and stabilizes infused
enzyme in the circulation.
Dr. Warnock said, "Migalastat HCl 150 mg co-administered with two different
doses of Fabrazyme, as well as one dose of Replagal, appeared to increase
enzyme activity compared to each of these ERTs alone. The use of a
pharmacological chaperone to maintain infused alpha Gal-A enzymes in optimally
active form represents a potential approach to managing ERT outcomes in
patients with Fabry disease."
Results were presented for a total of 12 patients who received migalastat HCl
150 mg co-administered with ERT (Fabrazyme in 8 patients and Replagal in 4
patients). Each patient received their current dose and regimen of ERT at one
infusion. A single oral dose of migalastat HCl 150 mg was co-administered two
hours prior to the next infusion of the same ERT at the same dose and regimen.
Due to the Fabrazyme supply difficulties during enrollment, 5 subjects had
been receiving 0.5 mg/kg Fabrazyme infused every two weeks and 3 subjects had
been receiving 1.0 mg/kg infused every four weeks. Four subjects were
receiving Replagal 0.2 mg/kg every two weeks.
Preliminary Results - Migalastat HCl 150 mg Co-Administered with ERT
(Fabrazyme and Replagal) (n=12)
*To date no serious adverse events or adverse events in this study have
been deemed related to migalastat HCl when co-administered with ERT. All
other treatment emergent adverse events were considered by the
investigators unrelated to study drug, and except for one incident of
severe paresthesia, were mild in intensity.
*Increases in levels of active enzyme in plasma in 12 out of 12 patients
demonstrated a drug-drug interaction between migalastat HCl 150 mg and
Fabrazyme, and between migalastat HCl 150 mg and Replagal. Increased
levels of active enzyme were observed in skin biopsy samples on day 2 and,
to a lesser extent, on day 7. The clinical significance of these results
are not yet known.
*Further investigations are being conducted with migalastat HCl 450 mg
co-administered with Fabrazyme and Replagal. Updated results are
anticipated in the first quarter 2013.
Alpha-Gal A Levels of Active Enzyme in Plasma Area Under the Curve (AUC)
Migalastat HCl + ERT vs. ERT Alone
No. of Migalastat HCl Dose ERT Mean Fold-Increase vs. ERT
Patients Alone (Range)
4 150 mg Replagal 0.2 mg/kg 4.4 (3.2 to 5.0)
5 150 mg Fabrazyme 0.5 mg/kg 3.0 (2.0 to 4.2)
3 150 mg Fabrazyme 1.0 mg/kg 2.0 (1.6 to 2.2)
Alpha-Gal A Levels of Active Enzyme in Skin at Days 2 and 7
Migalastat HCl + ERT vs. ERT Alone
Mean Fold-Increase vs. Mean Fold-Increase
No. of Migalastat ERT ERT vs. ERT
Patients HCl Dose Alone at Day 2 (Range) Alone at Day 7
4 150 mg Replagal 0.2 1.8 (1.4 to 2.3) 1.4 (1.1 to 1.8)
5 150 mg Fabrazyme 0.5 2.6 (1.1 to 3.9) 1.4 (0.7 to 2.8)
3 150 mg Fabrazyme 1.0 1.9 (1.6 to 2.1) 1.4 (1.2 to 1.7)
John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics
said, "We believe that this is a continued positive step forward in evaluating
this core aspect of our Amicus technology. These updated results from Study
013 support further investigation into the safety and efficacy of
chaperone-ERT co-administration. Early next year we look forward to having the
final results of this study."
About Study 013
Study 013 is an open-label Phase 2 drug-drug interaction study to evaluate the
safety and pharmacokinetic (PK) effects a single oral dose of migalastat HCl
(150 mg or 450 mg) co-administered with ERT (Fabrazyme^® or Replagal^®). Study
013 completed enrollment of 23 males with Fabry disease who are currently on
ERT. Each patient receives their regular dose and regimen of ERT. A single
oral dose of migalastat HCl is co-administered 2 hours prior to the next ERT
Enzyme activity is being measured in plasma (total area under the curve, or
AUC) during each infusion and in tissue (skin) following each infusion. In
published preclinical studies^1 migalastat HCl co-administered with ERT in
Fabry knock-out mice increased active enzyme in plasma and enzyme uptake into
skin, which led to further reductions in globotriaosylceramide (GL-3) compared
to ERT alone. For people living with Fabry disease, deficient alpha-Gal A
enzyme activity leads to the accumulation of globotriaosylceramide (GL-3) in
tissues affected by disease, including the kidney, heart and skin.
About Migalastat HCl
Amicus in collaboration with GlaxoSmithKline (GSK) is developing the
investigational pharmacological chaperone migalastat HCl for the treatment of
Fabry disease. Amicus has commercial rights to all Fabry products in the
United States and GSK has commercial rights to all of these products in the
rest of world.
As a monotherapy, migalastat HCl is designed to bind to and stabilize, or
"chaperone" a patient's own alpha-galactosidase A (alpha-Gal A) enzyme in
patients with genetic mutations that are amenable to this chaperone in a
cell-based assay. Migalastat HCl monotherapy is in Phase 3 development (Study
011 and Study 012) for Fabry patients with genetic mutations that are amenable
to this chaperone monotherapy in a cell-based assay. Study 011 is a
placebo-controlled study intended primarily to support U.S. registration, and
Study 012 compares migalastat HCl to ERT to primarily support global
For patients currently receiving ERT for Fabry disease, migalastat HCl in
combination with ERT may improve ERT outcomes by keeping the infused alpha-Gal
A enzyme in its properly folded and active form.
Migalastat HCl co-administered with ERT is in Phase 2 (Study 013) and
migalastat HCl co-formulated with JCR Pharmaceutical Co. Ltd's proprietary
investigational ERT (JR-051, recombinant human alpha-Gal A enzyme) is in
About Fabry Disease
Fabry disease is an inherited lysosomal storage disorder caused by deficiency
of an enzyme called alpha-galactosidase A (alpha-Gal A). The role of alpha-Gal
A within the body is to break down specific lipids in lysosomes, including
globotriaosylceramide (GL-3, also known as Gb3). Lipids that can be degraded
by the action of α-Gal are called "substrates" of the enzyme. Reduced or
absent levels of alpha-Gal A activity leads to the accumulation of GL-3 in the
affected tissues, including the kidneys, heart, central nervous system, and
skin. This accumulation of GL-3 is believed to cause the various symptoms of
Fabry disease, including pain, kidney failure, and increased risk of heart
attack and stroke.
It is currently estimated that Fabry disease affects approximately 5,000 to
10,000 people worldwide. However, several literature reports suggest that
Fabry disease may be significantly under diagnosed, and the prevalence of the
disease may be much higher.
About Amicus Therapeutics
Amicus Therapeutics (Nasdaq:FOLD) is a biopharmaceutical company at the
forefront of developing therapies for rare diseases. The Company is developing
orally-administered, small molecule drugs called pharmacological chaperones, a
novel, first-in-class approach to treating a broad range of human genetic
diseases. Amicus' late-stage programs for lysosomal storage disorders include
migalastat HCl monotherapy in Phase 3 for Fabry disease; migalastat HCl
co-administered with enzyme replacement therapy (ERT) in Phase 2 for Fabry
disease; and AT2220 co-administered with ERT in Phase 2 for Pompe disease.
This press release contains "forward-looking statements" within the meaning of
the Private Securities Litigation Reform Act of 1995 relating to clinical
development of Amicus' candidate drug products and the timing and reporting of
results from clinical trials evaluating Amicus' candidate drug products. Words
such as, but not limited to, "look forward to," "believe," "expect,"
"anticipate," "estimate," "intend," "plan," "targets," "likely," "will,"
"would," "should" and "could," and similar expressions or words identify
forward-looking statements. Such forward-looking statements are based upon
current expectations that involve risks, changes in circumstances, assumptions
and uncertainties. The inclusion of forward-looking statements should not be
regarded as a representation by Amicus that any of its plans will be achieved.
Any or all of the forward-looking statements in this press release may turn
out to be wrong. They can be affected by inaccurate assumptions Amicus might
make or by known or unknown risks and uncertainties. For example, with respect
to statements regarding the goals, progress, timing and outcomes of
discussions with regulatory authorities and the potential goals, progress,
timing and results of clinical trials, actual results may differ materially
from those set forth in this release due to the risks and uncertainties
inherent in the business of Amicus, including, without limitation: the
potential that results of clinical or pre-clinical studies indicate that the
product candidates are unsafe or ineffective; the potential that it may be
difficult to enroll patients in our clinical trials; the potential that
regulatory authorities may not grant or may delay approval for our product
candidates; the potential that preclinical and clinical studies could be
delayed because we identify serious side effects or other safety issues; the
potential that we will need additional funding to complete all of our studies
and, our dependence on third parties in the conduct of our clinical studies.
Further, the results of earlier preclinical studies and/or clinical trials may
not be predictive of future results. In addition, all forward looking
statements are subject to other risks detailed in our Quarterly Report on Form
10-Q for the quarter ended June 30, 2012. You are cautioned not to place undue
reliance on these forward-looking statements, which speak only as of the date
hereof. All forward-looking statements are qualified in their entirety by this
cautionary statement, and Amicus undertakes no obligation to revise or update
this news release to reflect events or circumstances after the date hereof.
This caution is made under the safe harbor provisions of Section21E of the
Private Securities Litigation Reform Act of 1995.
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