To investigative cipaglucosidase alfa/miglustat versus alglucosidase alfa/placebo in a randomized Phase III study (NCT03729362) of adults with LOPD.

Pompe disease is a rare disorder characterized by progressive loss of muscle and respiratory function due to acid α-glucosidase (GAA) deficiency. The approved treatment is enzyme-replacement therapy (ERT) with recombinant human GAA (rhGAA) alglucosidase alfa. Cipaglucosidase alfa/miglustat is an investigational, two-component therapy comprising cipaglucosidase alfa, a novel rhGAA, and miglustat, an enzyme stabilizer.

ERT-experienced (mean time on ERT = 7.4 years) and -naïve patients were randomized 2:1 to co-administration of cipaglucosidase (20 mg/kg) plus miglustat or alglucosidase alfa (20 mg/kg) plus placebo every 2 weeks. The primary and first key secondary endpoints were mean change from baseline to Week 52 in 6-minute walk distance (6MWD) and % predicted forced vital capacity (FVC), respectively. Subgroup analyses by baseline assessments: 6MWD (<300 m vs ≥300 m) and % predicted FVC (<55% vs ≥55%).

123 patients were randomized in 62 sites across 24 countries (cipaglucosidase alfa/miglustat, n=85; alglucosidase alfa, n=38). At Week 52, 6MWD showed a 14 m mean improvement with cipaglucosidase alfa/miglustat versus approved therapy but did not reach statistical superiority (P=0.072). Cipaglucosidase alfa/miglustat achieved a nominally statistically significant and clinically meaningful 3% mean improvement in % predicted FVC for superiority over approved therapy (P=0.023). Clinically significant improvements were noted in the ERT-experienced population with cipaglucosidase alfa/miglustat for both 6MWD (nominal P=0.046) and % predicted FVC (nominal P=0.006). Outcomes consistently favored cipaglucosidase alfa/miglustat in all subgroups for the overall and ERT-experienced populations, regardless of baseline 6MWD and % predicted FVC.

In this study population, cipaglucosidase alfa showed positive trends or clinically meaningful improvements on motor and respiratory functions compared with approved ERT, regardless of baseline 6MWD and % FVC assessments.