Switching Enzyme Replacement Therapy for Late-Onset Pompe Disease From Alglucosidase Alfa to Cipaglucosidase Alfa Plus Miglustat: Post Hoc Effect Size Analysis of PROPEL.

INTRODUCTION/AIMS: The randomized, double-blind PROPEL study (NCT03729362) suggested benefits for cipaglucosidase alfa plus miglustat (cipa+mig) versus alglucosidase alfa plus placebo (alg+pbo) in enzyme replacement therapy (ERT)-experienced adults with late-onset Pompe disease (LOPD). To further assess treatment response and the effect of switching treatment from alg to cipa+mig, we conducted a within-group effect size analysis in ERT-experienced patients. METHODS: In this post hoc analysis, standardized within-group effect sizes (Cohen's d for correlated measurements from baseline to week 52) were calculated by dividing the mean change from baseline by the corresponding standard deviation for motor function, lung function, and muscle strength outcomes; patient-reported outcomes/quality of life; and biomarker levels (creatine kinase and hexose tetrasaccharide). RESULTS: In PROPEL, 77% of patients received ERT with alg before study entry (median ERT duration 7.4 years). ERT-experienced patients remaining on alg+pbo (n = 30) generally showed within-group worsening (d ≤ -0.2) or stability (-0.2 < d < 0.2) across most outcomes, while those switched to cipa+mig (n = 65) mostly showed improvement (d ≥ 0.2) or stability. Patients remaining on alg+pbo demonstrated statistically significant worsening for several lung function outcomes, biomarker levels, and significant improvement for Patient-Reported Outcomes Measurement Information System (PROMIS)-Dyspnea. Patients switched to cipa+mig did not demonstrate significant worsening for any outcomes and showed significant improvements for 6-min walk distance (absolute and % predicted); upper, lower, and overall manual muscle testing; PROMIS-Fatigue; Physician (overall score) and Subject Global Impression of Change (5/8 subdomains); and biomarker levels. DISCUSSION: ERT-experienced patients with LOPD who switched from alg to cipa+mig treatment achieved improvements or stability in most outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03729362.

Duke Scholars

Author Priya Sunil Kishnani Pediatrics, Medical Genetics