Clinically important improvements in 6-minute walk distance and forced vital capacity in adults with late-onset Pompe disease switching from alglucosidase alfa to cipaglucosidase alfa plus miglustat in the PROPEL study.

We determined the proportion of adults with late-onset Pompe disease (LOPD) with clinically important changes in 6-minute walk distance (6MWD) and/or forced vital capacity (FVC) after switching from alglucosidase alfa (alg) to cipaglucosidase alfa plus miglustat (cipa+mig) in PROPEL (NCT03729362). This post hoc analysis (95 patients) used published anchor- and distribution-based minimal clinically important differences for 6MWD (in meters for anchor-based; % predicted for distribution-based) and a 3 % threshold for FVC (% predicted). For 6MWD, a higher percentage of patients improved after switching to cipa+mig versus alg plus placebo (alg+pbo) (anchor-based: 29.2 % versus 13.3 %; distribution-based: 33.8 % versus 13.3 %), fewer patients worsened (anchor-based: 12.3 % versus 26.7 %; distribution-based: 7.7 % versus 13.3 %). For FVC, 27.7 % versus 0.0 % improved for cipa+mig versus alg+pbo, 27.7 % versus 53.3 % worsened. Overall, 50.8 % versus 13.3 % of patients experienced improvements in 6MWD (% predicted) and/or FVC with cipa+mig versus alg+pbo, 30.8 % versus 56.7 % worsened. For combined responses from 6MWD (% predicted) and FVC (% predicted), the odds of a better versus a lower response category (improvement > stability > worsening) were 4.05 (95 % confidence interval 1.73-9.51) times higher for cipa+mig than alg+pbo (P = 0.0013). Adults with LOPD switching from alg to cipa+mig have greater chances of clinically relevant motor and lung function improvements than those remaining on alg.