Enzyme replacement therapies in adults with Pompe disease: from trials to real-world data

To review the clinical trial results and emerging real-world data of two new enzyme replacement therapies (ERTs) for late-onset Pompe disease and to compare these effects in the context of what has been achieved over the last two decades in advancing care for Pompe disease.

Randomized controlled trials (RCTs) of avalglucosidase alfa and cipaglucosidase alfa plus miglustat have demonstrated that both treatments are at least as efficacious as alglucosidase alfa and possess a comparable safety profile. Several post hoc analyses of the trial data have shown that these newer ERTs result in a greater percentage of patients achieving meaningful improvements and larger reductions in biomarker levels. The first real-world data on switching from alglucosidase alfa to avalglucosidase alfa has shown that the switch is safe and may alter individual disease trajectories.

The advent of two next-generation enzyme replacement therapies marks a new era in treating patients diagnosed with Pompe disease. Clinical trials and early real-world data suggest that they may be superior to alglucosidase alfa, the standard of care for the past 20 years, although head-to-head comparisons between all three treatments are lacking. More data will become available over the next 5 years, leading to better guidelines for starting, stopping and switching therapies based on a more personalized assessment of outcomes.