Single, Global Pivotal Trial to Support
Registration; Primary Endpoint of Arginine Reduction
Aeglea BioTherapeutics, Inc. (NASDAQ: AGLE), a clinical-stage
biotechnology company that designs and develops innovative human
enzyme therapeutics for patients with rare genetic diseases and
cancer, today announced the design of its global pivotal Phase 3
PEACE (Pegzilarginase Effect on Arginase 1 Deficiency Clinical
Endpoints) trial to evaluate the safety and efficacy of
pegzilarginase, the Company’s lead investigational therapy, in
patients with Arginase 1 Deficiency (ARG1-D). The Company has
aligned the trial design and endpoints with input from the U.S.
Food and Drug Administration (FDA) and the European Medicines
Agency (EMA), and plans to conduct a single, global pivotal trial
to support registration. Aeglea expects to dose the first patient
in the PEACE trial in the second quarter of 2019 and expects
topline data will be available in the first quarter of 2021.
PEACE is a global, randomized, double-blind
trial designed to assess the effects of treatment with
pegzilarginase versus placebo over 24 weeks with a primary endpoint
of statistically significant plasma arginine reduction from
baseline. The primary endpoint is intended to assess the
effectiveness of pegzilarginase in lowering plasma arginine levels
given the evidence that improved plasma arginine control has the
potential to improve the clinical status and slow disease
progression in patients with ARG1-D. Secondary endpoints assessing
changes in clinically meaningful outcomes including mobility,
adaptive behavior, safety and pharmacokinetics will be used to
describe the broader impact of pegzilarginase relative to placebo
on multiple aspects of ARG1-D.
“Arginine is the key driver of this devastating
disease and pegzilarginase is the first ever approach that has
demonstrated substantial lowering of plasma arginine levels,” said
Anthony G. Quinn, M.B Ch.B, Ph.D., president and chief executive
officer of Aeglea. “Finalization of our pivotal trial protocol
represents an important advance for ARG1-D patients who lack
effective treatment options. Our expectation is that the data from
the PEACE trial could be sufficient to support marketing
applications for pegzilarginase in ARG1-D.”
The company plans to enroll 30 (pediatric and
adult) patients with ARG1-D. Patients enrolled in the trial will be
randomized on a two-to-one basis to receive weekly infusions of
pegzilarginase (0.1 mg/kg), or placebo for the double-blind
treatment period of 24 weeks. Dose adjustments during this period
can be made to optimize plasma arginine control for levels outside
the range of 50 to 150 µM.
Patients will be considered eligible for the
PEACE trial if they exhibit average plasma arginine of greater than
250 µM, are greater than two years of age and have a deficit in
mobility or adaptive behavior. All assessments and dose adjustments
will be conducted in a blinded fashion at pre-specified intervals.
Patients will remain on current disease management for the duration
of the Phase 3 PEACE trial.
In addition to the primary endpoint of plasma
arginine reduction, secondary endpoints in the Phase 3 PEACE trial
will evaluate pegzilarginase relative to placebo through a
multi-dimensional assessment of clinical outcome. Measures of
clinical outcome are defined as a patient exhibiting improvement
from baseline in mobility (2 Minute Walk Test or Functional
Mobility Assessment) or adaptive behavior (Vineland Adaptive
Behavior Scale). Additional secondary endpoints include a response
rate for each individual assessment, the total number of mobility
and adaptive behavior responses per patient, the proportion of
patients with plasma arginine below medical guidance of 200 µM,
safety and pharmacokinetics.
“Patients with ARG1-D face chronic
hyperargininemia that results in significant morbidity and early
mortality. The PEACE trial is designed to determine the ability of
pegzilarginase to reduce elevated plasma arginine levels beyond
current management,” said James Wooldridge, M.D., chief medical
officer of Aeglea. “Thoughtful input from the FDA and EMA, and our
extensive analysis of Phase 1/2 data, resulted in a trial that is
designed to provide an assessment of the treatment effects of
pegzilarginase that are important to patients, clinicians and
regulators. Furthermore, we appreciate the growing support from the
patient and clinical community as we prepare to advance this
important trial.”
Throughout the PEACE trial, patients will be
monitored for adverse events. Upon completion of the 24-week
treatment period, patients will qualify to participate in a
long-term extension study of pegzilarginase.
Conference Call & Webcast
DetailsAeglea will hold a clinical update conference call
today, Tuesday, December 11, 2018 at 5:00 p.m. ET. To
access the live conference call via phone, please dial
1-877-709-8155 (toll free) within the United States, or
1-201-689-8881 internationally. A replay of the call will be
available through December 18, 2018 by dialing
1-877-660-6853 within the United States or 1-201-612-7415
internationally. The conference ID is 13685662.
To access the live and archived webcast of the
presentation, please visit the Presentations &
Events section of the Aeglea
BioTherapeutics investor relations website. Please connect to
the website at least 15 minutes prior to the presentation to allow
for any software download that may be necessary.
About Pegzilarginase in Arginase 1
Deficiency Pegzilarginase is an enhanced human arginase
that enzymatically depletes the amino acid arginine. Aeglea is
developing pegzilarginase for the treatment of patients with
Arginase 1 Deficiency, a rare debilitating disease presenting in
childhood with persistent hyperargininemia, severe progressive
neurological abnormalities and early mortality. Pegzilarginase is
intended for use as an enzyme replacement therapy in patients to
reduce elevated blood arginine levels. The Company’s interim Phase
1/2 data demonstrated clinical improvements and rapid and sustained
lowering of plasma arginine in Arginase 1 Deficiency patients.
About Aeglea BioTherapeutics
Aeglea is a clinical-stage biotechnology company that designs and
develops innovative human enzyme therapeutics for patients with
rare genetic diseases and cancer. The Company is developing
pegzilarginase, its lead investigational therapy, for the treatment
of Arginase 1 Deficiency, as monotherapy in arginine-dependent
cancers and in combination with an immune checkpoint inhibitor for
small cell lung cancer. In addition, Aeglea has an active research
pipeline of other human enzyme-based approaches in both therapeutic
areas. For more information, please visit http://aegleabio.com.
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. 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, (i) the
potential clinical and therapeutic benefits and economic value of
our lead product candidate, pegzilarginase or other product, (ii)
the initiation of patient dosing in the Phase 3 PEACE trial, (iii)
the ability of pegzilarginase to achieve applicable endpoints in
the Phase 3 PEACE trial, (iv) the ability for patients who
participate in the Phase 3 PEACE trial to participate in a
long-term extension study, (v) the availability of data from the
Phase 3 PEACE trial, and (vi) the potential for data from the
Company’s clinical trials of pegzilarginase to support a marketing
application, as well as the timing of these events Further
information on potential risk factors that could affect our
business and its financial results are detailed in our most recent
Quarterly Report on Form 10-Q for the quarter ended
September 30, 2018 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.
Media Contact: David
CalusdianSharon Merrill
Associates617.542.5300AGLE@investorrelations.com
Investor Contact: Joey Perrone
Director, Finance & Investor RelationsAeglea
BioTherapeuticsinvestors@aegleabio.com
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