Aeglea BioTherapeutics Announces Publication of 20 Week Data from Phase 1/2 and Open-Label Extension Studies of Pegzilarginase for the Treatment of Arginase 1 Deficiency in the Journal of Inherited Metabolic Disease


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

"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

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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