Mean
Six-Minute Walk Distance Improved in ERT-Naive Patients (+42 Meters
at 6 Months, +75 Meters at 9 Months) and ERT-Switch Patients (+35
Meters at 6 Months, +37 Meters at 9 Months)
Amicus Therapeutics (Nasdaq:FOLD) today announced additional
positive results from a global Phase 1/2 clinical study (ATB200-02)
to investigate ATB200/AT2221 in patients with Pompe disease, an
inherited lysosomal storage disorder caused by an enzyme deficiency
that leads to accumulation of glycogen (disease substrate) in
cells. Consistent with previous results, patients who completed six
months of treatment with ATB200/AT2221 showed improvements in
six-minute walk test (6MWT) distance and other measures of motor
function, stability or increases in forced vital capacity (FVC),
and further reductions in biomarkers of muscle damage and disease
substrate, with consistent results reported in initial patients who
completed nine months of treatment. These clinical results were
featured at the 22nd International Congress of the World Muscle
Society in a late-breaker poster1. With these data, Amicus plans to
continue a series of collaborative discussions with regulators in
the US and EU, and expects to provide an update in the first half
of 2018.
John F. Crowley, Chairman and Chief Executive
Officer of Amicus Therapeutics stated, “These remarkable data from
our Pompe clinical study of ATB200/AT2221 have once again exceeded
our expectations. The consistency, durability and magnitude of the
functional outcomes align with significant and continued reductions
in key biomarkers of muscle damage and disease substrate, across
patients, across cohorts and over significant periods of time.
Taken together the strength of these results suggest the effect of
ATB200/AT2221 may be very clinically meaningful for people living
with Pompe disease. We are committed to working collaboratively
with regulators to determine the fastest regulatory pathways that
may be available to bring this new treatment paradigm to as many
patients living with Pompe disease globally, as quickly as
possible.”
Mark Roberts, MD, Department of Neurology,
Salford Royal NHS Foundation Trust and Principal Investigator in
the ATB200-02 study stated, “I believe that the results from this
Phase 1/2 clinical study show striking improvements in functional
measures and key biomarkers during the first six months of
treatment, in addition to continued, further benefit out to nine
months. I am especially intrigued by the six-minute walk distance
and other motor function tests in the ERT-switch patients who
historically have declining motor function following two or more
years of treatment. These clinical data are compelling and suggest
that ATB200/AT2221 has the potential to shift the treatment
paradigm for Pompe disease.”
ATB200-02 Full Study Data – Highlights
in ERT-Switch and ERT-Naive Patients
Safety, Tolerability &
Pharmacokinetics (PK) (n=20)Safety and tolerability data
in all 20 patients reflect a maximum of 72 weeks of treatment. To
date, adverse events have been generally mild and transient.
Importantly, ATB200/AT2221 has resulted in a low rate of
infusion-associated reactions (IARs) following 400+ infusions
(three events of IARs in two patients; <1% of all 400+ infusions
with an IAR). As previously reported, the clinical pharmacokinetic
profile has been consistent with previously reported preclinical
data.
Pharmacodynamic (PD) Data on Muscle
Damage and Disease Substrate Biomarkers (n=20)Treatment
with ATB200/AT2221 resulted in reductions in key disease biomarkers
across all patient cohorts after up to 58 weeks and continue to
suggest a positive effect on muscle cells.
- Muscle damage biomarkers: Creatine kinase (CK)
enzyme, alanine aminotransferase (ALT), and aspartate
aminotransferase (AST), are biomarkers indicative of muscle damage
in Pompe disease. Mean reductions from baseline were approximately
25-35%, 5-25% and 40-55% for the ambulatory ERT-switch (n=11),
non-ambulatory ERT-switch (n=4) and ERT-naïve (n=5) patients,
respectively.
- Disease substrate biomarker: Urine hexose
tetrasaccharide (Hex4) is a biomarker of glycogen build-up. Mean
reductions from baseline were approximately 40%, 35% and 55% for
the ambulatory ERT-switch (n=11), non-ambulatory ERT-switch (n=4)
and ERT-naïve (n=5) patients, respectively.
Functional Outcomes (n=18)Data
on 6-month functional outcomes are available for 18 of the 20
patients enrolled (one patient dropped out of the extension study
due to travel burden and family considerations, while month 6
assessments are pending in one patient due to an incomplete visit).
Muscle function improved in 16 patients and was stable in two
patients at month 6. Muscle function improved in 10 out of 10
patients with available data at month 9.
- Muscle Function:
- Motor function (n=14): Six-minute walk test
(6MWT) distance, a primary measure of motor function in Pompe
disease patients, improved in both ERT-naive and ERT-switch
patients and was durable to month 9. ERT-naive patients showed mean
increases of 42 meters at month 6 (n=5) and 75 meters at month 9
(n=2). ERT-switch patients showed mean increases of 35 meters at
month 6 (n=9) and 37 meters at month 9 (n=8). Other motor function
tests showed mean improvements consistent with 6MWT
distance.
- Muscle Strength (n=4): All four non-ambulatory
ERT-switch patients showed improvements in upper extremity strength
(elbow and shoulder) from baseline to month 6, as measured by
quantitative muscle testing (QMT) and manual muscle testing
(MMT).
- Pulmonary Function: Forced vital capacity
(FVC), the primary measure of pulmonary function in Pompe disease,
improved in ERT-naïve patients, with mean absolute change in
percent predicted FVC of +4.2% at month 6 (n=5) and +5.0% at month
9 (n=2). FVC was generally stable in ERT-switch patients with mean
absolute change in percent predicted FVC of -1.0% at month 6 (n=8)
and -2.0% at month 9 (n=7). Other pulmonary tests included maximal
inspiratory pressure (MIP), a measure of inhalation, and maximal
expiratory pressure (MEP), a measure of exhalation. MIP and MEP
were generally stable or increased in both ERT-naïve and ERT-switch
patients.
Summary
of Functional Outcomes from Baseline to Month
6 Cohort
1 ERT-Switch Patients: Functional Outcomes on ATB200/AT2221 from
Baseline to Month 6 and 9
|
Motor Function Tests |
Pulmonary Function Tests |
|
6MWT (m) |
4 Stair Climb (sec) |
Timed up and go (sec) |
10m walk (sec) |
Gowers# |
GSGC Score |
FVC (%) |
MIP |
MEP |
Baseline Mean (SD) (n=10) |
397.2 (96.8) |
4.1(2.7) |
10.5(6.6) |
7.4(3.0) |
7.9(2.8) |
12.6(4.8) |
52.6(14.7) |
35.7(11.0) |
72.6(32.6) |
Change at Month 6 (SD)(n=9) |
+35.3 (40.1) |
-1.0(1.2) |
-2.2(3.4) |
-0.3(1.6) |
-2.2(2.0) |
-0.8(3.0) |
-1.0(4.2) |
+0.9(4.5) |
+20.3(42.4) |
Change at Month 9 (SD)(n=8) |
+37.2(33.8) |
-0.9(1.3) |
-0.6 (2.5) |
0.1(1.3) |
-2.1(1.3) |
-0.9(3.5) |
-2.0(3.6) |
-1.4(2.7) |
+31.1(39.3) |
Cohort 3 ERT-Naïve Patients: Functional Outcomes on
ATB200/AT2221 from Baseline to Month 6 and 9
|
Motor Function Tests |
Pulmonary Function Tests |
|
6MWT (m) |
4 Stair Climb (sec) |
Timed up and go (sec) |
10m walk (sec) |
Gowers# |
GSGC Score |
FVC (%) |
MIP |
MEP |
Baseline Mean (SD) (n=5) |
399.5(83.5) |
4.2(1.5) |
9.4(2.9) |
7.9(3.0) |
13.9(11.0) |
12.2(3.6) |
53.4(20.3) |
32.6(18.5) |
60.6(8.3) |
Change at Month 6 (SD)(n=5) |
+41.8(29.4) |
-0.6(0.3) |
-1.0(1.1) |
-0.7(1.1) |
7.9*(21.0) |
-1.8(3.8) |
+4.2(5.6) |
+11.0(5.0) |
-0.4(12.4) |
Change at Month 9 (SD)(n=2) |
+74.9(4.0) |
-0.8(0.3) |
-1.6(1.0) |
-1.0(0.1) |
-1.3(0.0) |
-4.0(1.4) |
+5.0(1.4) |
+1.5(0.7) |
-1.0(19.8) |
*Median change from baseline was -0.8 and 4/5
had decrease; # N=9 Missing values not obtained due to patient
refusal to perform test
Conference Call and WebcastAmicus Therapeutics
will host a conference call and webcast today, October 4, 2017 at
8:30 a.m. ET. Interested participants and investors may access the
conference call by dialing 877-303-5859 (U.S./Canada) or
678-224-7784 (international); conference ID 96220532. The slide
presentation to accompany this conference call and webcast will be
available at http://ir.amicusrx.com/events.cfm.
An audio webcast can also be accessed via the Investors section
of the Amicus Therapeutics corporate web site at
http://ir.amicusrx.com/events.cfm, and will be archived for 30
days. Web participants are encouraged to go to the web site 15
minutes prior to the start of the call to register, download and
install any necessary software. A telephonic replay of the call
will be available for seven days beginning at 11:30 a.m. ET today.
Access numbers for this replay are 855-859-2056 (U.S./Canada) and
404-537-3406 (international); conference ID 96220532.
About ATB200-02 Clinical
StudyThe primary objectives of the open-label ATB200-02
clinical study are to evaluate the safety, tolerability,
pharmacokinetics (PK), and pharmacodynamics (PD) of ATB200/AT2221
over an 18-week primary treatment period followed by a long-term
extension. Sixteen clinical sites in five countries participated in
the ATB200-02 clinical study. The study enrolled a total of 20
patients at 16 participating sites in five countries across three
patient cohorts: ambulatory ERT-switch (Cohort 1, n=11),
non-ambulatory ERT-switch (Cohort 2, n=4) and ERT-naïve (Cohort 3,
n=5). Patients in Cohort 1 received escalating doses of ATB200 (5,
10, 20 mg/kg), followed by 3 doses of 20 mg/kg ATB200 plus low dose
AT2221, followed by ongoing doses of 20 mg/kg ATB200 plus high dose
AT2221. Patients in Cohort 2 and 3 patients have all received 20
mg/kg ATB200 plus high dose AT2221.
About
ATB200/AT2221ATB200/AT2221 is a novel treatment paradigm
that consists of ATB200, a unique recombinant human acid
alpha-glucosidase (rhGAA) enzyme with optimized carbohydrate
structures, particularly mannose-6 phosphate (M6P), to enhance
uptake, co-administered with AT2221, a pharmacological chaperone.
In preclinical studies, ATB200 was associated with increased tissue
enzyme levels and reduced glycogen levels in muscle, which was
further improved when AT2221 was co-administered with ATB200.
Amicus Therapeutics is currently conducting a global Phase 1/2
study (ATB200-02) to evaluate the safety, tolerability,
pharmacokinetics (PK) and pharmacodynamics of ATB200/AT2221.
About Pompe DiseasePompe
disease is an inherited lysosomal storage disorder caused by
deficiency of the enzyme acid alpha-glucosidase (GAA). Reduced or
absent levels of GAA leads to accumulation of glycogen in cells,
which is believed to result in the clinical manifestations of Pompe
disease. Pompe disease can be debilitating, and is characterized by
severe muscle weakness that worsens over time. Pompe disease ranges
from a rapidly fatal infantile form with significant impacts to
heart function to a more slowly progressive, late-onset form
primarily affecting skeletal muscle. It is estimated that Pompe
disease affects approximately 5,000 to 10,000 people worldwide.
For more information, download our Pompe
disease infographic.
About Amicus Therapeutics
Amicus Therapeutics (Nasdaq:FOLD) is a global biotechnology company
at the forefront of therapies for rare and orphan diseases. The
Company has a robust pipeline of advanced therapies for a broad
range of human genetic diseases. Amicus’ lead programs in
development include the small molecule pharmacological chaperone
migalastat as a monotherapy for Fabry disease, as well as novel
enzyme replacement therapy (ERT) and biologic products for Fabry
disease, Pompe disease, and other rare and devastating
diseases.
Forward-Looking StatementsThis
press release contains "forward- looking statements" within the
meaning of the Private Securities Litigation Reform Act of 1995,
including statements relating to encouraging preliminary data from
a global Phase 1/2 study to investigate ATB200/AT2221 for the
treatment of Pompe and the potential implications on these
data for the future advancement and development of ATB200/AT2221.
Words such as, but not limited to, “look forward to,” “believe,”
“expect,” “anticipate,” “estimate,” “intend,” "confidence,"
"encouraged," “potential,” “plan,” “targets,” “likely,” “may,”
“will,” “would,” “should” and “could,” and similar expressions or
words identify forward-looking statements. The forward looking
statements included in this press release are based on management's
current expectations and belief's which are subject to a number of
risks, uncertainties and factors, including that the
preliminary data based on a small patient sample and reported
before completion of the study will not be predictive
of future results, that results of additional preliminary
data or data from the completed study or any future study
will not yield results that are consistent with the preliminary
data presented, that the Company will be not able to
demonstrate the safety and efficacy of ATB200/AT2221, that
later study results will not support further
development, or even if such later results are favorable,
that the Company will not be able to successfully complete
the development of, obtain regulatory approval for, or successfully
commercialize ATB200/AT2221. In addition, all forward
looking statements are subject to the other risks and uncertainties
detailed in our Annual Report on Form 10-K for the year ended
December 31, 2016 and Quarterly Report on 10-Q for the Quarter
ended June 30, 2017. As a consequence, actual results may
differ materially from those set forth in this press release.
You are cautioned not to place undue reliance on these forward
looking statements, which speak only of the date hereof. All
forward looking statements are qualified in their entirety by this
cautionary statement and we undertake no obligation to revise this
press release to reflect events or circumstances after the date
hereof.
1Roberts, et. al., 22nd International
Congress of the World Muscle Society, First-in-Human Study
of ATB200/AT2221 in Patients With Pompe Disease: Interim Results
From the ATB200-02 Trial
CONTACTS:
Investors/Media:Amicus
TherapeuticsSara Pellegrino, IRCSenior Director, Investor
Relationsspellegrino@amicusrx.com (609) 662-5044
Media:Jennifer Paganelli Media
Relations jpaganelli@purecommunications.com (347) 658-8290
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