P373 Effect size analysis of cipaglucosidase alfa + miglustat versus alglucosidase alfa in ERT-experienced adults with late-onset Pompe disease in PROPEL

The randomized, double-blind PROPEL study (ATB200-03; NCT03729362) compared the efficacy and safety of the investigational 2-component enzyme replacement therapy (ERT) cipaglucosidase alfa+miglustat (cipa+mig) with alglucosidase alfa+placebo (alg) 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/quality of life; 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; PROMIS fatigue; physician and subject global impression of change (5 of 8 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. The randomized, double-blind PROPEL study (ATB200-03; NCT03729362) compared the efficacy and safety of the investigational 2-component enzyme replacement therapy (ERT) cipaglucosidase alfa+miglustat (cipa+mig) with alglucosidase alfa+placebo (alg) 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/quality of life; 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; PROMIS fatigue; physician and subject global impression of change (5 of 8 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.