First multicenter real-world analysis of switching to next-generation enzyme replacement therapies in late-onset Pompe disease

TL;DR

This study examines the real-world outcomes of switching enzyme replacement therapies in late-onset Pompe disease, finding that transitions are generally feasible and maintain clinical stability.

Contribution

The study provides the first multicenter real-world evidence on switching next-generation enzyme replacement therapies in late-onset Pompe disease.

Findings

Transitions between enzyme replacement therapies were associated with stable respiratory function and minimal changes in activity levels.

No significant effects of time or switch type were observed, with baseline performance being the main predictor of outcomes.

Switching therapies was generally feasible and linked to clinical stability in patients with late-onset Pompe disease.

Abstract

Next-generation enzyme replacement therapies (ERTs) for late-onset Pompe disease (LOPD), including avalglucosidase alfa and cipaglucosidase alfa with miglustat, have been developed to improve muscle targeting and enzyme stability. Real-world evidence on therapy switching between ERT preparations remains limited.

A prospective, observational, multicenter cohort study was conducted across German neuromuscular centers. Adults with genetically confirmed LOPD who transitioned to avalglucosidase alfa (Aval) or cipaglucosidase alfa with miglustat (Cipa/Mig) between August/2022 and September/2024 were included. Clinical data were extracted from medical records using a standardized case report form. Following EPOC recommendations, data captured comprised six-minute walk test (6MWT), ten-meter walk test (10MWT), Rasch-built Pompe-specific Activity scale (R-PAct), upright and supine forced vital capacity (FVC), maximal inspiratory/expiratory pressure (MIP/MEP), and maximal voluntary ventilation (MVV). Data were analyzed descriptively and using linear mixed-effects models. Paired comparisons between baseline and 12 months were performed as a secondary analysis in patients with available data.

Thirty-nine patients (43 switches; alglucosidase alfa (AlGlu) → Aval n = 32, AlGlu → Cipa/Mig n = 7) were included; four double switches were analyzed under AlGlu → Aval. Main reasons for switching were patient request (42%) and clinical worsening (40%). Overall data completeness declined over time. Mean trajectories indicated stable respiratory function, minimal change in R-PAct, and non-significant trends toward slower walking performance. Mixed-model analyses revealed no significant effects of time or switch type, with baseline performance as the only consistent predictor. Infusion-related or serious adverse events were rare, and EPOC documentation criteria were met in 56% of patients.

This real-world study suggests that transitions between ERT preparations are generally feasible and associated with clinical stability in LOPD. Switching may represent a useful strategy in patients, particularly when efficacy concerns arise. Standardized prospective studies with systematic monitoring of immunogenicity and efficacy according to the 2024 EOPC guideline are recommended to confirm these findings.

The online version contains supplementary material available at 10.1007/s00415-026-13689-1.

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