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

• Published in: Muscle & nerve Vol. 72; no. 2; pp. 230 - 239
• Main Authors: Kushlaf, Hani, Díaz‐Manera, Jordi, Bratkovic, Drago, Byrne, Barry J., Claeys, Kristl G., Clemens, Paula R., Dimachkie, Mazen M., Kishnani, Priya S., Laforêt, Pascal, Roberts, Mark, Schoser, Benedikt, Toscano, Antonio, Castelli, Jeff, Holdbrook, Fred, Sitaraman Das, Sheela, Goldman, Mitchell, Mozaffar, Tahseen
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.08.2025; Wiley Subscription Services, Inc
• Subjects: 1-Deoxynojirimycin - administration & dosage; 1-Deoxynojirimycin - analogs & derivatives; 1-Deoxynojirimycin - therapeutic use; Adult; Aged; alpha-Glucosidases - therapeutic use; Biomarkers; cipaglucosidase alfa; Creatine; Creatine kinase; Double-Blind Method; Dyspnea; Enzyme Replacement Therapy - methods; Enzymes; Fatigue tests; Female; Glycogen Storage Disease Type II - drug therapy; Health services; Human motion; Humans; Kinases; late‐onset Pompe disease; Lungs; Male; Middle Aged; miglustat; Muscle strength; Muscle Strength - drug effects; Muscular fatigue; Patients; Quality of Life; Respiration; Respiratory function; Stability; Statistical analysis; Treatment Outcome; cipaglucosidase alfa; late‐onset Pompe disease; miglustat
• ISSN: 0148-639X; 1097-4598; 1097-4598
• DOI: 10.1002/mus.28420

ABSTRACT 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 A total of 95 ERT‐experienced adults with LOPD were randomized to switch to cipaglucosidase alfa + miglustat or remain on alglucosidase alfa treatment. After 52 weeks, patients remaining on alglucosidase alfa showed worsening or stability for most outcomes, whereas patients who switched to cipaglucosidase alfa + miglustat generally showed stability or improvement.