treatment frequency reduction in pompe disease

Conditions: Pompe Disease (Late-onset); GAA Deficiency; Glycogen Storage Disease Type II; Acid Maltase Deficiency

Summary: the aim of this study is to assess if dosing frequency reduction of alglucosidase alfa 20 mg/kg once every 2 weeks to once every 4 weeks is safe and does not lead to increased progression of disease in a selected group of patients with late-onset pompe disease.

all eligible patients with late-onset pompe disease will be treated with alglucosidase alfa 20 mg/kg once every 4 weeks for 9 months. during the study, patients will be monitored once every 3 months. after 9 months of treatment with the extended interval, it will be determined for each patient whether it is considered safe to discontinue enzyme replacement therapy (ert). the investigators consider it safe: 1\] if the patient is stable compared to the year prior to reducing the ert frequency, or, 2\] if the patient previously deteriorated (slightly) despite standard ert and this deterioration is not exaggerated by the alternative dosing regimen. if after 9 months there is no valid medical reason to switch back to standard dosing (once every 2 weeks) and the patient does not wish to discontinue treatment, the 4-week dosing regimen will be continued. if at any moment a patient shows an unexpectedly rapid decline in clinical outcome parameters (significantly higher than their own course at regular treatment dosage), treatment will be switched back to or be restarted with the standard dosing regimen of 20 mg/kg every 2 weeks. both, patients who stop ert after 9 months and those who continue with either the new or the previous dosing schedule, will be closely followed for an additional 12 months to be able to take action (e.g., switch to a standard dosing regimen or restart ert) if a more rapid clinical deterioration occurs than expected, or to investigate if muscle and pulmonary function regain when standard dosage has been re-instituted after signs of clinical deterioration during the 4-week treatment interval. after the end of the study (21 months), patients will be carefully followed according to the standard frequency (once every 6 months). if a patient shows an unexpectedly rapid decline in clinical outcome parameters henceforth, treatment will be switched back to or be restarted with the standard dosing regimen of 20 mg/kg eow.

Eligibility criteria:
inclusion criteria: * lopd (confirmed diagnosis: enzyme deficiency in any tissue source and/or 2 confirmed disease-causing variants in the gaa gene) * age ≥50 years * current treatment with alglucosidase alfa at a standard dose of 20 mg/kg once every 2 weeks for ≥4 years * relatively stable clinical condition over the past year * able to walk ≥150 m within 6 minutes (6mwt) * (forced) vital capacity (fvc) in sitting position: \>55% of expected value and in supine position: \>45% of expected value * willing and able to adhere to the study procedures exclusion criteria: * rapidly progressive muscle weakness * severely limited muscle strength almost requiring/requiring daily wheelchair use * requiring respiratory support (non-invasive/invasive ventilation) or being at high risk to require respiratory support (ventilation) due to further deterioration of current pulmonary function. using continuous positive airway pressure (cpap) support only for obstructive sleep apnea syndrome (osas) is permitted. * comorbidities which are expected to influence the primary outcome measures within the next 2 years