Late-Onset Pompe Disease: Next Protocol When Alglucosidase Alfa Dose Escalation Fails to Stabilise Skeletal Muscle and Respiratory Function
This protocol applies to patients with late-onset Pompe disease — presenting after the age of one year during childhood or adulthood — in whom dose escalation of first-line therapy has not achieved stabilisation or improvement of skeletal muscle and respiratory function.
Clinical scenario
Late-onset Pompe disease manifests at any age after infancy, with proximal (limb girdle) myopathy that leads to progressive motor disability and waddling gait. Cardiac involvement is absent in this late-onset form. The degree of motor disability is more closely related to disease duration than to the patient's age at presentation.
Previous treatment — failure condition
Dose escalation of
Alglucosidase alfa was used in late-onset patients showing a suboptimal response, plateau, or clinical decline at the standard dose. This protocol is indicated when that escalation strategy has not resulted in
stabilisation or improvement of skeletal muscle and respiratory function — the defined goals of the previous treatment line.
Next step (partial overview)
When the above goals are not met after an adequate period on escalated first-generation enzyme replacement therapy, the protocol considers a switch to a
second-generation enzyme replacement therapy (ERT). The specific agents, any combination regimens, and all administration details are available in the full protocol.
Primary clinical target: Improvement of percent predicted forced vital capacity (FVC).
References
DOI: 10.1186/s13023-024-03373-w
Patients may present at any age, but mostly after the age of 1 year during childhood or adulthood.
They usually present with proximal (limb girdle) myopathy leading to progressive motor disability (more closely related to disease duration than to the age of the patient), with waddling gait, mostly without cardiac involvement.
Switching to a second-generation ERT can be considered if there is no indication of skeletal muscle and/or respiratory function stabilization or improvements after at least a year on first-generation recombinant alpha-glucosidase, or if the patient suffers from severe infusion-associated reactions that cannot be adequately managed.
Compared to alglucosidase alfa plus placebo, cipaglucosidase alfa plus miglustat probably improves % predicted FVC compared to alglucosidase alfa plus placebo.
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