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

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.