AUSTIN, Texas, July 14, 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 the publication of 20 week data from the Phase 1/2
clinical trial of pegzilarginase for the treatment of Arginase 1
Deficiency (ARG1-D), a rare, progressive and devastating disease
characterized by high levels of the amino acid arginine.
Pegzilarginase is a novel, recombinant human arginase 1 enzyme
designed to lower levels of arginine that is also being
investigated in PEACE, an ongoing Phase 3 pivotal trial for the
treatment of ARG1-D.
The article, titled "Clinical Effect and Safety Profile of
Pegzilarginase In Patients with Arginase 1 Deficiency," was lead
authored by Dr. George Diaz, Division Chief of Medical
Genetics in the Department of Genetics & Genomic
Sciences at the Icahn School of Medicine at Mt.
Sinai, New York, NY, and has been
published in the July issue of the Journal of Inherited
Metabolic Disease. The full publication can be accessed at
https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.12343.
"This trial is the first time clinical outcomes have been used
to assess the impact of ARG1-D and provides critical information in
our understanding of the disease burden and potential for its
treatment," said Dr. Diaz. "Given the serious and progressive
nature of this condition, understanding how to limit or even
reverse the course of the disease has the potential to
fundamentally alter how we treat ARG1-D and improve the lives of
patients and their families."
The Phase 1/2 trial was designed to assess the safety and
efficacy of pegzilarginase for the treatment of ARG1-D. These
results represent data after only 20 doses of pegzilarginase. Key
results from the study include:
- Pegzilarginase was well tolerated, and the rates of
treatment-related adverse events decreased over time.
-
- Common treatment-related adverse events included
hypersensitivity, vomiting, hyperammonemia, pruritus and abdominal
pain.
- Serious treatment-related adverse events included
hypersensitivity and hyperammonemia, which were infrequent, managed
with standard treatment and did not lead to any patient
discontinuations.
- All patients demonstrated a marked and sustained reduction in
plasma arginine.
-
- By Dose 20, 13 of 14 (93%) patients had arginine levels <200
µM and seven patients had arginine levels within the normal range
(40-115 µM). 200 µM is the clinical goal level used at present,
which is rarely achieved through currently available treatment
options.
- Eleven of 14 (79%) patients demonstrated improvements equal to
or greater than the minimal clinically important difference (MCID)
in one or more of three mobility assessments.
"People living with ARG1-D face an immense burden from their
disease every day with mobility challenges, intellectual
disability, and apprehension about disease progression and a
shortened life. The publication of these results in a peer reviewed
journal mark an important validation for this program and we are
very pleased to see that 79% of patients treated with
pegzilarginase showed evidence of clinical improvements,"
said Anthony G. Quinn, M.B. Ch.B., Ph.D., president and chief
executive officer of Aeglea. "The very high clinical responder rate
in this Phase 1/2 trial using these assessments similar to those in
PEACE, our pivotal Phase 3 study, gives us high confidence in our
clinical program and its potential to demonstrate the effectiveness
of pegzilarginase as a treatment option for people living with
ARG1-D."
About the Phase 1/2 and Open-Label Extension Studies
The multicenter, global clinical trial enrolled 16 patients
diagnosed with Arginase 1 Deficiency aged 2 years or older. Data
are reported from the 12-week Phase 1/2 study (n=16) and the first
12 weeks of an open-label extension study. The Phase 1/2 study was
conducted in two parts. In Part 1, patients received single
ascending intravenous (IV) doses of pegzilarginase at 2-week
intervals. In Part 2, patients received eight weekly repeat IV
doses of pegzilarginase. After completion of the Phase 1/2 study,
patients were eligible to enroll in the open-label extension study
which consisted of weekly administration of subcutaneous (SC) doses
of pegzilarginase. Patients in the trial continued to receive
standard treatment approaches. The open-label extension study is
ongoing.
The primary endpoint of the study was assessment of safety and
tolerability of pegzilarginase. Additional endpoints included
decrease from baseline in plasma arginine level as well as mobility
assessments, including 6MWT (Six-minute Walk Test) and GMFM (Gross
Motor Function Measure) Part D and Part E. A Responder was defined
based on a ≥1 MCID improvement in at least one of the three key
mobility assessments.
About Pegzilarginase in Arginase 1 Deficiency
Pegzilarginase is a novel recombinant human enzyme, 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 patients 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
patients with ARG1-D demonstrated clinical improvements and
sustained lowering of plasma arginine. The Company's ongoing
single, global pivotal Phase 3 PEACE trial is designed to assess
the effects of treatment with pegzilarginase versus placebo over 24
weeks with a primary endpoint of plasma arginine reduction.
Pegzilarginase has received multiple regulatory designations,
including Rare Pediatric Disease, Breakthrough, 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 a pivotal
Phase 3 trial for the treatment of Arginase 1 Deficiency and has
received both Rare Pediatric Disease and Breakthrough Therapy
Designations. The Company began dosing patients in a Phase 1/2
clinical trial of AGLE-177 for the treatment of Homocystinuria in
June 2021. AGLE-177 has also 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. For more information, please visit http://aeglea.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 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, 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 its
financial results are detailed in our most recent Quarterly Report
on Form 10-Q for the quarter ended March 31,
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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