A disease progression model comparing the long-term mobility and respiratory outcomes of adults with late-onset Pompe disease receiving cipaglucosidase alfa plus miglustat versus alglucosidase alfa.

Aim: Late-onset Pompe disease (LOPD) is a rare lysosomal disease primarily impacting muscle strength and respiratory function. LOPD has a substantial burden despite the availability of alglucosidase alfa (alg). Patients often require mobility and respiratory support over time. Cipaglucosidase alfa in combination with miglustat (cipa + mig) is one of two more recently approved treatments for adults with LOPD. Given limited data on the lifetime trajectory to mobility and respiratory support in LOPD, a patient-level simulation model was developed to compare the long-term impact of cipa + mig with alg on these outcomes. Materials & methods: The patient-level simulation predicts lifetime mobility and respiratory disease progression outcomes based on the 6-min walk distance and %predicted forced vital capacity for alg and cipa + mig for the overall LOPD population using available data and assumptions from experienced clinicians. PROPEL/PROPEL open-label extension (NCT03729362) and ATB200-02 (NCT02675465) studies informed outcomes for four years with cipa + mig and one year with alg. French Pompe disease registry data were used thereafter. Results: Based on the available data and clinical assumptions, the model predicts cipa + mig slows the overall progression of LOPD, allowing patients an additional 2.72 years without mobility or respiratory support compared with alg. People receiving alg may be wheelchair dependent and require invasive respiratory support for an additional 2.57 and 1.55 years, respectively. Conclusion: Cipa + mig may delay disease progression compared with alg over the lifetime of a patient with LOPD, which would increase the amount of time spent without mobility and respiratory support dependency.