Aeglea BioTherapeutics Readies to Begin Pivotal Phase 3 in Arginase 1 Deficiency

December 13, 2018

Rare Daily Staff

Aeglea BioTherapeutics said after discussions with regulators in the United States and Europe, it plans to conduct a single pivotal phase 3 clinical study to support registration of its lead experimental therapy pegzilarginase as a treatment for Arginase 1 Deficiency (ARG1-D).

Arginase 1 Deficiency is a rare debilitating and life-threatening urea cycle disorder. It causes hyperarginaemia, or excessively high levels of arginine in the blood because of an enzyme deficiency. It presents in early childhood with a range of neurological symptoms and early mortality. Aside from severe dietary protein restriction, there is no treatment that addresses the root cause of the disease to help prevent the progressive spasticity, seizures, impaired growth, intellectual disability, and other serious symptoms of this condition.

Pegzilarginase is an enhanced human arginase that enzymatically depletes the amino acid arginine. 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. The company expects to dose the first patient in the trial in the second quarter of 2019 and expects topline data will be available in the first quarter of 2021.

The study will be 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 Quinn, president and CEO of Aeglea. “Finalization of our pivotal trial protocol represents an important advance for ARG1-D patients who lack effective treatment options.”


December 13, 2018
Photo: Anthony Quinn, president and CEO of Aeglea

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