Real‐World Effectiveness and Safety of Pegzilarginase Treatment in Arginase 1 Deficiency

ABSTRACT Pegzilarginase is the first disease‐modifying drug for arginase 1 deficiency. In clinical trials, pegzilarginase effectively normalised plasma arginine (pArg), which was associated with clinically relevant improvements in neuromotor outcomes. We report from a French early access scheme the first report on experience from pegzilarginase therapy outside a clinical trial. Sixteen patients were started in the programme between September 2022 and September 2024. Six had previously participated in a clinical trial (PCT) and 10 were treatment naïve (TN). Clinical data was collected at baseline, after 3 months, and then 6‐monthly. Mean pegzilarginase exposure was 78.9 weeks. Fourteen patients had been treated for ≥ 12 months. At the 3‐month follow‐up, mean pArg had dropped from 430 to 128 μmol/L (70%) for the TN group and from 168 to 107 μmol/L (36%) for the PCT group. Interestingly, one patient discontinued after 69 weeks of therapy due to absence of decrease of pArg despite stepwise increase of dose. After discontinuation of pegzilarginase, the presence of anti‐drug antibodies (ADAs) was confirmed. For the whole cohort, average daily intake of dietary protein increased from 0.61 to 0.91 g/kg/day during the first 12 months ( p = 0.02). No firm conclusions could be drawn from quality‐of‐life data, but trends were positive. In conclusion, our results are in line with what has been previously reported from clinical trials.