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

Aims Enzyme replacement therapy (ERT) for mucopolysaccharidosis II (MPS II) involves long-term weekly intravenous infusions often lasting over 3 hours each, which burdens paediatric patients and caregivers and can negatively affect their quality of life and treatment compliance. This study’s aim was to determine whether shortening infusion durations affects the long-term efficacy and safety of ERT. Methods A post-hoc pharmacodynamic analysis was conducted using 260-week clinical data on 27 Japanese patients with MPS II who participated in a phase II/III clinical trial and an extension study of pabinafusp alfa administered at a dose of 2.0 mg/kg/week following a switch from prior ERT with idursulfase. Safety was assessed through the incidence of adverse events, side effects, and infusion-associated reactions, and efficacy was evaluated on the basis of heparan sulfate and dermatan sulfate concentrations in the cerebrospinal fluid (CSF), serum, and urine, along with neurocognitive development and liver and spleen volumes. The weekly infusion duration was ≥3 hours until Week 52, after which discretionary shortening was permitted. Results Shorter infusion times did not correlate with increased infusion-associated reactions or other adverse events. Substrate levels in the CSF, serum, and urine, as well as liver and spleen volumes, remained stable irrespective of infusion rates, indicating sustained therapeutic efficacy. Conclusions Infusion rate adjustments did not significantly affect the safety or efficacy of ERT with pabinafusp alfa in patients with MPS II, indicating that clinicians can have flexibility to shorten infusion times as appropriate to improve patients’ quality of life and treatment compliance.