Effect Size Analysis of Cipaglucosidase Alfa Plus Miglustat Versus Alglucosidase Alfa in ERT-experienced Adults with Late-onset Pompe Disease in PROPEL
Hani Kushlaf1, Drago Bratkovic2, Barry Byrne3, Kristl Claeys4, Jordi Diaz-Manera5, Mazen Dimachkie6, Priya Kishnani7, Mark Roberts8, Antonio Toscano9, Jeff Castelli10, Frederick Holdbrook10, Sheela Das10, Yasmine Wasfi10, Benedikt Schoser11, Tahseen Mozaffar12
1University of Cincinnati, 2PARC Research Clinic, Royal Adelaide Hospital, 3University of Florida, 4Department of Neurology, University Hospitals Leuven, and Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, 5John Walton Muscular Dystrophy Research Centre, Newcastle University, 6Department of Neurology, University of Kansas Medical Center, 7Duke University Medical Center, 8Salford Royal NHS Foundation Trust, 9ERN-NMD Center for Neuromuscular Disorders of Messina, Department of Clinical and Experimental Medicine, University of Messina, 10Amicus Therapeutics, Inc., 11Friedrich-Baur-Institute at the Department of Neurology, LMU University Hospital, LMU Munich, 12Department of Neurology, University of California
To analyze within-group effect sizes of cipaglucosidase alfa plus miglustat (cipa+mig) and alglucosidase alfa (alg) for efficacy, quality of life (QoL), and biomarker variables in ERT-experienced patients.
The randomized, double-blind PROPEL study (ATB200-03; NCT03729362) compared the efficacy and safety of the investigational two-component enzyme replacement therapy (ERT) cipa+mig with alg plus placebo in adults with late-onset Pompe disease (LOPD); 77% of patients had received ERT with alg before study entry (median ERT duration 7.4 years). 
We analyzed within-group effect sizes of cipa+mig and alg for outcome variables including motor function, lung function and muscle strength tests; patient-reported outcomes/QoL; and biomarkers in ERT-experienced patients. 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 standard deviation of the difference scores. 
ERT-experienced patients remaining on alg (n=30) generally showed worsening (d<−0.2) or stability (−0.2≤d≥+0.2) across most outcomes, while those switching to cipa+mig (n=65) mostly showed improvement (d>0.2) or stability. Patients remaining on alg demonstrated statistically significant within-group worsening for sitting and supine forced vital capacity; slow vital capacity; maximal expiratory pressure; and creatine kinase (CK) and hexose tetrasaccharide (Hex4) levels, and no significant improvements for any outcomes. Patients switching to cipa+mig did not demonstrate significant within-group worsening for any outcomes and showed significant improvements for 6-minute walk distance (absolute and % predicted); upper, lower and overall manual muscle test; Patient-Reported Outcomes Measurement Information System (PROMIS)−Fatigue; Physician and Subject Global Impression of Change (five of eight subdomains); and CK and Hex4 levels. 

This analysis shows that ERT-experienced patients with LOPD who switched from alg to cipa+mig treatment achieved improvements in a number of outcomes, highlighting the potential of cipa+mig to become an important treatment option for these patients. Sponsored by Amicus Therapeutics Inc.