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Efficacy and safety of pegzilarginase in patients below 2 years of age with arginase 1 deficiency: a phase 3, open-label, multi-centre study

Year: 2026

Type: article

Abstract: Background: Arginase 1 Deficiency (ARG1-D) is a rare metabolic disorder characterized by marked hyperargininaemia and progressive neurological impairment. Dietary protein restriction alone is often insufficient to normalize plasma arginine (pArg) or prevent disease progression. Pegzilarginase, a recombinant human ARG1 enzyme therapy, has demonstrated pArg normalization and improved clinical outcomes in patients ≥2 years. This study evaluated safety, pharmacokinetics (PK), and activity of pegzilarginase in patients <2 years. Methods: In this phase 3, open-label, single-arm study (NCT06582524, EU CT 2024-510797-25), conducted in United Kingdom, Austria and Portugal, patients received once-weekly subcutaneous pegzilarginase. As primary endpoint, change in pArg at 12 weeks was assessed. Secondary endpoints included safety, PK, plasma ornithine and Gross Motor Function Measure (GMFM-66). Descriptive analyses were performed on the Full Analysis Set. Findings: Three patients (mean age 20.3 months) were included between 30 August 2024 and 17 June 2025. After 12 weeks, mean (SD) pArg decreased by 221.5 (81.3) μmol/L, a 70.6% (4.3) reduction, reaching normal range by Visit 4 (114.1 [68.4] μmol/L). Plasma ornithine increased and plasma ammonia remained largely normal. GMFM-66 total scores improved by 21.0 (13.9) points (18.1% [5.8%]). Pegzilarginase exposure was consistent with previous studies; AUC and half-life were similar, whereas clearance and volume of distribution were lower, as expected in infants. No new safety findings were observed. Interpretation: In patients with ARG1-D <2 years of age, pegzilarginase demonstrated pharmacokinetic and pharmacodynamic responses comparable to older children and a favourable safety profile. Funding: Immedica Pharma AB.

Source: EClinicalMedicine

DOI: 10.1016/j.eclinm.2026.104021

Authors: Arunabha Ghosh, Anna Baghdasaryan, Patricia Lipari Pinto, Mattias Rudebeck