Amicus Therapeutics (Nasdaq: FOLD) today announced additional
positive results from a global Phase 1/2 clinical study (ATB200-02)
to investigate AT-GAA in adult patients with Pompe disease, an
inherited lysosomal storage disorder caused by an enzyme deficiency
that leads to accumulation of glycogen (disease substrate) in
cells. The U.S. Food and Drug Administration (FDA) previously
granted Breakthrough Therapy Designation (“BTD”) to AT-GAA for the
treatment of late onset Pompe disease based on clinical efficacy
results this Phase 1/2 clinical study, including improvements in
six-minute walk distance in late onset Pompe patients and
comparison to natural history of treated patients.
Patients treated with AT-GAA for 24 months showed persistent and
durable effects on six-minute walk test (6MWT) distance and other
measures of motor function and muscle strength, stability or
increases in forced vital capacity (FVC), and reductions in
biomarkers of muscle damage and disease substrate. Consistent with
these 24-month results, positive impacts on the same measures of
motor and pulmonary function and key biomarkers were also observed
after 3-15 months of treatment in an additional group of six
ambulatory ERT switch patients that had been on standard of care
ERT for at least seven years prior to switching to AT-GAA. (Cohort
4).
These clinical results are being featured at the 24th
International Annual Congress of the World Muscle Society in an
oral platform presentation on Friday October 4, 2019 at 10:00am
CEST (4:00am EDT). The presentation will be given by Professor
Benedikt Schoser, senior consultant at the
Friedrich-Baur-Institute, Dept. of Neurology at the
Ludwig-Maximilians-University of Munich, Germany and Principal
Investigator in the ATB200-02 study. These results are also
available in a presentation on the Amicus corporate website and
will be highlighted during the Amicus Analyst Day on October 10,
2019.
John F. Crowley, Chairman and Chief Executive Officer of Amicus
Therapeutics stated, “We are very pleased to report the latest data
for AT-GAA. Collectively these data continue to represent
meaningful and durable improvements in functional outcomes, in
addition to persistent reductions in key biomarkers of muscle
damage and disease substrate. Compared to what is known about the
natural history of both untreated and ERT-experienced patients,
these results give great hope that AT-GAA has the potential to
become the new standard of care for people living with Pompe. These
results also provide further support and confidence in the overall
study design and powering of our ongoing pivotal PROPEL study.”
Dr. Schoser stated, “There is a clear need for a new treatment
option to address multiple aspects of Pompe disease across a broad
spectrum of Pompe patients, including previously untreated and
ERT-switch patients as well as non-ambulatory patients. The twenty
four month results from this Phase 1/2 clinical study of AT-GAA
continue to demonstrate a robust effect in adult people living with
Pompe disease, including improvements in six minute walk distance
among ambulatory ERT-switch and ERT-naïve participants and
sustained positive changes in arm and shoulder strength among the
non-ambulatory ERT-switch patients. These new data in the Cohort 4
patients are particularly impressive showing the potential for
AT-GAA to change the course of the disease in these patients. I
look forward to continuing to follow patients from this Phase 2
study in addition to the ongoing PROPEL pivotal study.”
ATB200-02 Study Data Highlights in ERT-Switch and
ERT-Naive Patients Out to Month 24
Cohort 1 – 3 (n=22)Complete 24-month data was
presented for 18 out of 22 patients enrolled in the initial three
study cohorts, including ERT-switch ambulatory patients (n=11),
ERT-switch non-ambulatory patients (n=6), and ERT-naïve patients
(n=5).
Functional Outcomes (n=18)*: Muscle function
improved in 16 out of 18 patients at 24 months.
- Motor function: Six-minute walk test (6MWT), a
primary measure of motor function in Pompe disease patients,
improved in both ERT-naive and ERT-switch patients with continued
benefit observed out to month 24. Improvements were generally
consistent across both cohorts.
- All 5 ERT-naive patients showed increases in 6MWT distance at
all time points out to month 24. The ERT-naïve patients showed mean
increases of 42 meters at month 6 (n=5), 63 meters at month 12
(n=5), and 61 meters at month 24 (n=5).
- 6MWT increased in 7/10, 9/10, and 8/9 ERT-switch patients in
Cohort 1 at Months 6, 12, and 24 respectively. The ERT-switch
patients in Cohort 1 showed mean increases of 24 meters at month 6
(n=10), 42 meters at month 12 (n=10), and 36 meters at month 24
(n=9).
- Other motor function tests generally showed mean improvements
consistent with 6MWT distance out to month 24 in all ambulatory
cohorts.
- Muscle Strength: Ambulatory and non-ambulatory
ERT-switch patients showed improvements in strength testing as
assessed by manual muscle testing (MMT) from baseline to month 24.
Quantitative muscle testing (QMT) results were generally consistent
with MMT.
- Pulmonary Function: Pulmonary function
improved in ERT-naïve patients and was generally stable in
ERT-switch patients.
- In ERT-naïve patients, mean absolute change in forced vital
capacity (FVC), one of the main measures of pulmonary function in
Pompe disease, was +4.2% at month 6 (n=5), +4.5% at month 12 (n=5),
and +6.8% at month 24 (n=5).
- In ERT-switch patients in Cohort 1, mean absolute change in FVC
was -1.2% at month 6 (n=9), -3.0% at month 12 (n=9), and +0.9% at
month 24 (n=8).
- Overall, other pulmonary tests of maximal inspiratory pressure
(MIP), a measure of inhalation, and maximal expiratory pressure
(MEP), a measure of exhalation, were stable or increased in both
ERT-naïve and ERT-switch patients across all cohorts.
Cohort 4 (n=6)A fourth cohort of six additional
ERT-switch ambulatory patients was subsequently added to the study.
At the time of the data analysis, five patients have available data
at month 6. The last available timepoint includes all six patients
after 3-15 months of treatment, with one subject at Month 3, two
subjects at Month 6, two subjects at Month 12 and one subject at
Month 15.
- Motor Function: Muscle function improved in
2/5 patients at month 6 and 4/6 patients at the last available time
point:
- Historical data on 6MWT for the six patients showed an average
decline of approximately 7 meters per year while on standard of
care ERT prior to switching to AT-GAA (n=6), with 5/6 patients
declining.
- After switching to AT-GAA, the patients in Cohort 4 showed mean
increases of 24 meters at month 6 (n=5) and 19 meters at their last
available timepoint (n=6). 6MWT increased in 2/5 patients at month
6 and 4/6 patients at the last available time point.
- Other motor function tests generally showed mean improvements
consistent with 6MWT distance at month 6 (n=5) and at their last
available timepoint (n=6).
- All patients showed improvements in strength testing from
baseline to month 6 and at the last available timepoint, as
measured by quantitative muscle testing (QMT) and manual muscle
testing (MMT).
- Pulmonary Function: Pulmonary function
improved at month 6 (n=5) and at the last available time point
(n=6).
- After switching to AT-GAA, FVC increased in 5/6 patients at
month 6 and 5/6 patients at the last available time point. Mean
absolute change in FVC was +6.6% at month 6 (n=5) and +5.2% at the
last available time point (n=6).
- Overall, other pulmonary tests of maximal inspiratory pressure
(MIP), a measure of inhalation, and maximal expiratory pressure
(MEP), a measure of exhalation, were stable or increased in all
patients at month 6 (n=5) and at the last available timepoint
(n=6).
Safety, Tolerability and
Pharmacokinetics/Pharmacodynamics (PK/PD) in Cohorts 1-4
(n=28)
- Safety and tolerability data reflect a maximum of 40 months of
treatment. To date, adverse events have been generally mild and
transient.
- AT-GAA has resulted in a low rate of infusion-associated
reactions (IARs) following 1,500+ infusions (28 incidents of IARs
in 8 patients; 1.8% of all 1,500+ infusions with an IAR).
- The clinical pharmacokinetic profile has been consistent with
previously reported preclinical data.
- Persistent and durable reductions in key biomarkers of muscle
damage (creatine kinase, or CK) and disease substrate (urine hexose
tetrasaccharide, or Hex4) across all patient cohorts out to month
24 continue to suggest a positive effect on muscle tissue.
- Anti-GAA antibodies were observed in the majority of Cohort 1
and Cohort 3 patients from baseline to month 24. There was no
impact of antibodies on safety, efficacy and exposure or clearance
of ATB200. Data on impact of antibodies for Cohorts 2 and 4 are not
currently available.
AT-GAA Development and Regulatory StrategyThe
Company’s strategy is to enhance the body of clinical data for
AT-GAA in ongoing clinical studies, including the pivotal study
(PROPEL, also referred to as ATB200-03) to deliver this potential
new therapy to as many people living with Pompe disease as soon as
possible. Based on feedback from US and EU regulatory authorities,
Amicus expects the PROPEL study to support approval for a broad
indication, including ERT-switch and treatment-naïve patients.
Anticipated Pompe Milestones:
- Presentation of 24-month and Cohort 4 Phase 2 results at Amicus
Analyst Day on October 10, 2019.
- Additional supportive studies, including an open-label study in
pediatric patients.
- Full enrollment in Phase 3 PROPEL study in 2019.
- Advance agreed upon CMC requirements to support BLA.
- Publication of Phase 1/2 clinical results.
*Discontinuations were as follows: Cohort 1 (n=2 out of 11):
travel burden (after 18 weeks), withdrawal of consent (not related
to treatment) (after month 18). Cohort 2 (n=1 out of 6): IAR (after
month 18 - 4 IARs, generally urticarial rash, with nasopharyngeal
edema on 1 occasion. Baseline values not obtained in one patient in
Cohort 2. No discontinuations in Cohorts 3 or 4.
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 originally enrolled a total of 20
patients across three patient cohorts: ambulatory ERT-experienced
(Cohort 1, n=11), non-ambulatory ERT-experienced (Cohort 2, n=4)
and ERT-naïve (Cohort 3, n=5); in addition two more patients were
enrolled in cohort 2. A fourth cohort of 6 ambulatory ERT-switch
patients was also been enrolled, adding to the patient data in the
ambulatory ERT-switch population. 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 Cohorts 2, 3,
and 4 all receive 20 mg/kg ATB200 plus high dose AT2221.
About AT-GAAAT-GAA is an investigational
therapy 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, AT-GAA was associated with increased tissue
enzyme levels, reduced glycogen levels in muscle, and improvements
in muscle strength. A global Phase 1/2 study (ATB200-02) is ongoing
to evaluate the safety, tolerability, pharmacokinetics (PK) and
pharmacodynamics of AT-GAA.
Amicus has also initiated a global Phase 3
clinical study (ATB200-03, or PROPEL) of AT-GAA in adult patients
with late onset Pompe disease. PROPEL is a 52-week, double-blind
randomized study designed to assess the efficacy, safety and
tolerability of AT-GAA compared to the current standard of care,
alglucosidase alfa, an enzyme replacement therapy (ERT). More
information, including a list of participating sites, is available
at www.clinicaltrials.gov: NCT03729362.
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. The
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.
About Amicus TherapeuticsAmicus Therapeutics
(Nasdaq: FOLD) is a global, patient-dedicated biotechnology company
focused on discovering, developing and delivering novel
high-quality medicines for people living with rare metabolic
diseases. With extraordinary patient focus, Amicus Therapeutics is
committed to advancing and expanding a robust pipeline of
cutting-edge, first- or best-in-class medicines for rare metabolic
diseases. For more information please visit the company’s website
at www.amicusrx.com, and follow us on Twitter and LinkedIn.
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 preliminary data from a global Phase 1/2
study to investigate AT-GAA for the treatment of Pompe and the
potential implications on these data for the future advancement and
development of AT-GAA. 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 AT-GAA, 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 AT-GAA. 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, 2018 and
Quarterly Report on 10-Q for the Quarter ended June 30, 2019. 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.
CONTACTS:
Investors:Amicus TherapeuticsSara Pellegrino,
IRCVice President, Investor Relations spellegrino@amicusrx.com(609)
662-5044
Media:Christopher Byrne Executive Director,
Corporate Communications cbyrne@amicusrx.com609-662-2798
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