Navigating Treatment Switch in Late-Onset Pompe Disease (LOPD)

This symposium, ‘A case-based approach to navigating treatment switch in late-onset Pompe Disease (LOPD)’, was held at the 21st WORLDSymposium from the 3rd–7th February 2025, in San Diego, California, USA. Speakers discussed some of the unmet needs for patients living with LOPD, used clinical cases to highlight key considerations for navigating a treatment switch, and presented data on cipaglucosidase alfa + miglustat for enzyme replacement therapy (ERT)-experienced adults living with LOPD. LOPD is a lysosomal disorder caused by a deficiency of the acid alpha glucosidase (GAA) enzyme which leads to progressive glycogen accumulation in muscle. As a multisystemic, progressive, heterogeneous disease, LOPD can lead to irreversible muscle damage and weakness, reducing a person’s ability to move and breathe. The ERT alglucosidase alfa has been the cornerstone of LOPD management since 2006, but waning efficacy in some patients, typically after 3–5 years, creates a need for additional treatment options. Three key mechanistic challenges exist that could result in suboptimal delivery of enzymes to tissues: enzyme stability in the blood stream, enzyme uptake into the muscle cells, and enzyme activity in the lysosome. During the symposium, the speakers, experts in the management of LOPD, explored how second generation treatment options may help address current unmet needs, and how shared-decision making and holistic monitoring can support informed treatment decisions in certain adults with LOPD. They reviewed key data on cipaglucosidase alfa + miglustat for ERT-experienced adults living with LOPD, and shared their insights on the management of treatment switching using clinical cases.