Infusion rate adjustment in enzyme replacement therapy with pabinafusp alfa for mucopolysaccharidosis II

AIMS: Enzyme replacement therapy (ERT) for mucopolysaccharidosis II (MPS II) requires long-term, weekly intravenous infusions often lasting over 3 h each time, which can burden paediatric patients and caregivers and negatively affect their quality of life and treatment compliance. The aim of this study was to assess whether shortening infusion duration impacts the long-term efficacy and safety of ERT. METHODS: A post hoc analysis was conducted using 260 weeks of clinical data from 27 Japanese patients with MPS II who received pabinafusp alfa at a dose of 2.0 mg/kg/week during a Phase II/III clinical trial and an extension study. Individual adjustments to the weekly infusion duration were allowed only during the extension study. Safety was assessed through the incidence of adverse events and infusion-associated reactions, while efficacy was evaluated by measuring heparan sulfate and dermatan sulfate levels in the cerebrospinal fluid (CSF), serum and urine, as well as assessing liver and spleen volumes and neurocognitive development scores. RESULTS: Shorter infusion times were not associated with increased infusion-associated reactions or other adverse events. Heparan sulfate and dermatan sulfate levels in the CSF, serum and urine, as well as liver and spleen volumes were not affected by changes in infusion rates, indicating sustained therapeutic efficacy. CONCLUSIONS: Infusion rate adjustments were not associated with notable changes in the safety or efficacy of ERT with pabinafusp alfa in patients with MPS II. Clinicians may safely consider decreasing infusion times on a case-by-case basis to improve patients' quality of life and treatment compliance.