AUSTIN, Texas, Dec. 6, 2021 /PRNewswire/ -- Aeglea
BioTherapeutics, Inc. (NASDAQ: AGLE), a clinical-stage
biotechnology company developing a new generation of human enzyme
therapeutics as innovative solutions for rare metabolic diseases,
today announced that the pivotal Phase 3 study, PEACE
(Pegzilarginase Effect on Arginase 1 Deficiency Clinical
Endpoints), met the primary endpoint with a statistically
significant reduction in plasma arginine from baseline after 24
weeks of treatment with pegzilarginase (p <0.0001). Importantly,
pronounced and sustained plasma arginine reduction was accompanied
by a positive trend in Gross Motor Function Measure Part E
(GMFM-E), a key clinical assessment of a patient's mobility,
including the ability to walk, run and jump.
PEACE is the first placebo-controlled clinical trial ever
conducted in Arginase 1 Deficiency (ARG1-D) and pegzilarginase is
the first potential therapy to normalize the markedly elevated
plasma arginine levels in these patients. Based on the results of
this trial, Aeglea plans to submit a Biologics License Application
(BLA) to the U.S. Food and Drug Administration (FDA) in the first
half of 2022. Additionally, Aeglea will work with Immedica Pharma
AB, its commercial partner in Europe and certain countries in the
Middle East, to submit marketing
authorization applications in those territories.
"I have been treating children born with ARG1-D for 20 years and
what we are experiencing with pegzilarginase has truly given us a
renewed sense of optimism. These children and their families live
with a daily burden of not only managing the progressive
manifestations of the disease, including mobility limitations,
intellectual disability and behavior challenges, but also a
burdensome standard of care. A better treatment paradigm for these
patients is desperately needed," said Dr. George Diaz,
Director, Program for Inherited Metabolic Disorders at Mount
Sinai Hospital, New York, NY and
PEACE trial principal investigator. "Clinicians recognize the
importance of effective arginine control, and I am delighted that
the PEACE pivotal trial demonstrated that pegzilarginase lowered
plasma arginine to normal levels and also showed a positive trend
in an important mobility assessment of clinical benefit. I believe
that, with early diagnosis and treatment intervention, families
have a new reason to hope."
ARG1-D is a rare, progressive and debilitating disease
characterized by high levels of the amino acid arginine. The
disease manifestations include spasticity, developmental delay,
intellectual disability and seizures. The functional disability and
impact on daily life creates a significant burden for patients and
caregivers. There are currently no FDA-approved treatments
that address elevated arginine, the key driver of ARG1-D. Current
standard of care includes severe dietary protein restriction and
essential amino acid supplementation, which does not effectively or
sustainably reduce high arginine levels.
PEACE is a global, randomized, double-blind, placebo-controlled
trial that enrolled 32 patients with ARG1-D aged two years and
older. The study was designed to assess the effects of treatment
with pegzilarginase (n=21) versus placebo (n=11) from baseline
through a prespecified 24-week treatment period. The primary
endpoint assessed plasma arginine reduction from baseline levels.
The key secondary endpoint evaluated mobility using GMFM-E, which
consists of 24 tasks involving walking forward/backward, running,
jumping and ascending/descending stairs, and the 2-Minute Walk Test
(2MWT), a measure of the distance a patient walks in two minutes.
Other secondary endpoints included additional outcome assessments,
safety and pharmacokinetics. Topline results are summarized as
follows:
- PEACE demonstrated a highly statistically significant 80%
reduction in mean plasma arginine in pegzilarginase treated
patients (p<0.0001), the primary endpoint of the trial.
Importantly, normal plasma arginine levels (40-115µM) were achieved
in 90.5% of pegzilarginase treated patients compared to none of the
patients in the placebo arm.
- The least squares mean GMFM-E score improved by 4.2 units for
pegzilarginase treated patients and worsened by 0.4 units in the
placebo arm (p=0.1087; 95% CI [-1.1, 10.2]), establishing a
positive trend in this mobility assessment. The least squares mean
2MWT distance increased 7.4 meters in pegzilarginase treated
patients and 1.9 meters in the placebo arm (p=0.5961; 95% CI
[-15.6, 26.7]).
- Pegzilarginase was well-tolerated and safety data were
consistent with results from previous clinical trials. There were
no study discontinuations due to adverse events.
All 31 patients who completed the 24-week double-blind study
period continued into the Long-Term Extension (LTE) portion of the
PEACE trial. In addition, 13 of the 14 patients in the ongoing
Phase 1/2 Open Label Extension (OLE) trial have continued
pegzilarginase therapy ranging from 2 to 4 years. The previously
presented 56-week data from the Phase 1/2 OLE trial supports the
long-term clinical benefit of pegzilarginase treatment. The company
believes that the entirety of data from the pegzilarginase program
supports the long-term clinical benefit of pegzilarginase in
ARG1-D. Additional data from the pegzilarginase program are
expected to be presented at upcoming medical meetings and submitted
to peer-reviewed medical journals.
"I would like to thank the patients and their caregivers,
investigators and staff, and our employees for their contributions
to the study. The dramatic reduction in plasma arginine levels
and the positive trend in GMFM-E are very encouraging and represent
an important step in our mission to bring a transformative therapy
to this underserved patient community," said Anthony G. Quinn, M.B., Ch.B., Ph.D., president
and chief executive officer of Aeglea. "We believe that today's
announcement demonstrates validation of our scientific platform,
overall pipeline and potential to address other rare metabolic
diseases."
Conference Call
Investors and the public are invited
to listen to a live audio webcast of the conference call, scheduled
for December 6, 2021, at 8:00am ET, which may be accessed five minutes
prior to the start of the call by
dialing 1-877-425-9470 (U.S.)
or 1-201-389-0878 (International) Conference ID
13725511 or through the Events & Presentations section of
the Company's website.
To access live and/or archived Investor Conference webcasts,
visit the Events & Presentations section of the
Company's website. A replay of Company webcasts is archived on the
website for 60 days following presentations.
About the PEACE Phase 3 Study
PEACE is a single,
global, randomized, double-blind, placebo-controlled trial that
enrolled 32 patients aged 2 years and older with Arginase 1
Deficiency in the United States,
Canada and Europe (NCT03921541). PEACE was designed to
assess the effects of treatment with pegzilarginase versus placebo
over 24 weeks with a primary endpoint of plasma arginine reduction
from baseline. Secondary endpoints include clinical outcome
assessments focused on several mobility assessments, in addition to
safety and pharmacokinetics. Patients were randomized on a
two-to-one basis to receive weekly infusions of pegzilarginase or
placebo for the double-blind 24-week treatment period.
About Pegzilarginase in Arginase 1
Deficiency
Pegzilarginase is a novel recombinant human
enzyme engineered to degrade the amino acid arginine and which
has been shown to rapidly and sustainably lower levels of the amino
acid arginine in plasma. Aeglea is developing pegzilarginase for
the treatment of people with Arginase 1 Deficiency (ARG1-D), a rare
debilitating and progressive disease characterized by the
accumulation of arginine. ARG1-D presents in early childhood and
patients experience spasticity, seizures, developmental delay,
intellectual disability and early mortality.
Aeglea's Phase 1/2 and Phase 2 Open Label Extension (OLE) data
for pegzilarginase in people with ARG1-D demonstrated clinical
improvements and sustained lowering of plasma arginine.
Pegzilarginase has received multiple regulatory designations,
including Rare Pediatric Disease, Breakthrough Therapy, Fast Track
and Orphan Drug Designations from the U.S. Food and Drug
Administration as well as Orphan Drug Designation from the European
Medicines Agency.
About Aeglea BioTherapeutics
Aeglea BioTherapeutics is
a clinical-stage biotechnology company redefining the potential of
human enzyme therapeutics to benefit people with rare metabolic
diseases with limited treatment options. Aeglea's lead product
candidate, pegzilarginase, is in an ongoing Phase 3 pivotal trial
in patients with Arginase 1 Deficiency and has received both Rare
Pediatric Disease and Breakthrough Therapy designations. Aeglea has
an ongoing Phase 1/2 clinical trial of AGLE-177 for the treatment
of Homocystinuria. AGLE-177 has been granted Rare Pediatric Disease
Designation. Aeglea has an active discovery platform focused on
engineering small changes in human enzymes to have a big impact on
the lives of patients and their families.
Safe Harbor / Forward Looking Statements
This press
release contains "forward-looking" statements within the meaning of
the safe harbor provisions of the U.S. Private Securities
Litigation Reform Act of 1995. Forward-looking statements can be
identified by words such as: "anticipate," "intend," "plan,"
"goal," "seek," "believe," "project," "estimate," "expect,"
"strategy," "future," "likely," "may," "should," "will" and similar
references to future periods. These statements are subject to
numerous risks and uncertainties that could cause actual results to
differ materially from what we expect. Examples of forward-looking
statements include, among others, statements we make regarding our
ability to obtain regulatory approval for, and commercialize,
pegzilarginase, recognize milestone and royalty payments from our
agreement with Immedica, the timing and success of our clinical
trials and related data, the timing and expectations for regulatory
submissions and approvals, including the submission of a BLA for
pegzilarginase, timing and results of meetings with regulators, the
timing of announcements and updates relating to our clinical trials
and related data, our ability to enroll patients into our clinical
trials, the expected impact of the COVID-19 pandemic on our
operations and clinical trials, success in our collaborations, our
cash forecasts, the potential addressable markets of our product
candidates and the potential therapeutic benefits and economic
value of our lead product candidate or other product candidates.
Further information on potential risk factors that could affect our
business and financial results are detailed in our Annual Report on
Form 10-K for the year ended December 31,
2020 and our most recent Quarterly Report on Form 10-Q for
the quarter ended September 30, 2021
filed with the Securities and Exchange Commission (SEC), and other
reports as filed with the SEC. We undertake no obligation to
publicly update any forward-looking statement, whether written or
oral, that may be made from time to time, whether as a result of
new information, future developments or otherwise.
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SOURCE Aeglea BioTherapeutics, Inc.