Clinical effect and safety profile of pegzilarginase in patients with arginase 1 deficiency

George A. Diaz, Andreas Schulze, Markey C. McNutt, Elisa Leão-Teles, J. Lawrence Merritt, Gregory M. Enns, Spyros Batzios, Allison Bannick, Roberto T. Zori, Leslie S. Sloan, Susan L. Potts, Gillian Bubb, Anthony G. Quinn

Research output: Contribution to journalArticlepeer-review


Hyperargininemia in patients with arginase 1 deficiency (ARG1-D) is considered a key driver of disease manifestations, including spasticity, developmental delay, and seizures. Pegzilarginase (AEB1102) is an investigational enzyme therapy which is being developed as a novel arginine lowering approach. We report the safety and efficacy of intravenously (IV) administered pegzilarginase in pediatric and adult ARG1-D patients (n = 16) from a Phase 1/2 study (101A) and the first 12 weeks of an open-label extension study (102A). Substantial disease burden at baseline included lower-limb spasticity, developmental delay, and previous hyperammonemic episodes in 75%, 56%, and 44% of patients, respectively. Baseline plasma arginine (pArg) was elevated (median 389 μM, range 238-566) on standard disease management. Once weekly repeat dosing resulted in a median decrease of pArg of 277 μM after 20 cumulative doses (n = 14) with pArg in the normal range (40 to 115 μM) in 50% of patients at 168 hours post dose (mean pegzilarginase dose 0.10 mg/kg). Lowering pArg was accompanied by improvements in one or more key mobility assessments (6MWT, GMFM-D & E) in 79% of patients. In 101A, seven hypersensitivity reactions occurred in four patients (out of 162 infusions administered). Other common treatment-related adverse events (AEs) included vomiting, hyperammonemia, pruritus, and abdominal pain. Treatment-related serious AEs that occurred in five patients were all observed in 101A. Pegzilarginase was effective in lowering pArg levels with an accompanying clinical response in patients with ARG1-D. The improvements with pegzilarginase occurred in patients receiving standard treatment approaches, which suggests that pegzilarginase could offer benefit over existing disease management.

Original languageEnglish (US)
JournalJournal of Inherited Metabolic Disease
StateAccepted/In press - 2020


  • ARG1-D
  • arginase 1 deficiency
  • human enzyme
  • hyperammonemia
  • hyperargininemia
  • pegzilarginase
  • spasticity

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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