Rare Daily Staff
In mid-October, Aeglea BioTherapeutics, a company that designs and develops innovative human enzyme therapeutics for patients with rare genetic diseases and cancer, presented new positive interim clinical data at the 2018 American Society of Human Genetics Conference from its ongoing phase 1/2 trial of pegzilarginase, its lead investigational enzyme replacement therapy for the treatment of arginase 1 deficiency, a rare, debilitating urea cycle disorder.
Arginase 1 deficiency presents in childhood. A genetic mutation results in an enzyme deficiency with persistent hyperargininemia, severe progressive neurological abnormalities and early mortality. The condition causes elevated levels of arginine and ammonia in the blood, and leads to severe, progressive, neurological abnormalities and early mortality.
The standard of care has been a low- protein diet. Pegzilarginase is an enhanced human arginase that enzymatically depletes arginine. Aeglea’s interim phase 1/2 data demonstrated clinical improvements in mobility and adaptive behavior, and rapid and sustained lowering of plasma arginine in Arginase 1 Deficiency patients after eight doses.
“Our clinical experience with ARG1-D and pegzilarginase has advanced rapidly given the accelerated enrollment over the last few months. The developing efficacy profile is compelling, particularly given the short period of repeat dosing,” said Anthony G. Quinn, president and CEO of Aeglea.
All six study patients who were repeatedly dosed achieved consistent levels of reduced arginine in the blood, and 67 percent of patients had clinically meaningful improvements in mobility and/or adaptive behavior after only eight weeks of repeat dosing with pegzilarginase. The therapy was well tolerated and adverse events were mild and manageable.
“The arginine control we’ve seen with pegzilarginase in this study is remarkable – it’s well beyond what we have been able to achieve with the standard management of patients with Arginase 1 Deficiency,” said Andreas Schulze, professor of pediatrics and biochemistry at the University of Toronto and section head of Metabolic Genetics at the Hospital for Sick Children in Toronto. “I’m truly encouraged by the improvements I have seen in one of our younger patients in terms of communication and walking, and I’m excited about moving the development of pegzilarginase into a pivotal study for patients with this rare and challenging disorder.”
In early October, the U.S. Food and Drug Administration granted rare pediatric disease designation to pegzilarginase for the treatment of arginase 1 deficiency.
November 5, 2018
Photo: Anthony Quinn, president and CEO of Aeglea BioTherapeutics