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

10 Scopus citations


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)
Pages (from-to)847-856
Number of pages10
JournalJournal of Inherited Metabolic Disease
Issue number4
StatePublished - Jul 2021


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

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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