Recommendations issued on Pompe disease treatment switching
Updated guidance also covers starting, stopping LOPD treatments
A group of experts in Europe published updated recommendations for late-onset Pompe disease (LOPD) treatment, including for the first time guidance about switching between different approved treatments.
The recommendations were published in the European Journal of Neurology in a paper titled, “Start, switch and stop (triple-S) criteria for enzyme replacement therapy of late-onset Pompe disease: European Pompe Consortium recommendation update 2024.”
Pompe is caused by mutations that lead to deficiency of the enzyme acid alpha-glucosidase. This enzyme is normally needed to break down the sugar molecule glycogen. In Pompe, deficiency of the enzyme leads to toxic buildup of glycogen in cells, driving disease symptoms. Enzyme replacement therapies (ERTs) are medications designed to deliver a working version of the dysfunctional enzyme.
The European Pompe Consortium is a group of more than two dozen Pompe experts from across eight countries in Europe. In 2017, the consortium published recommendations for when to start and stop ERT. At the time, Myozyme (alglucosidase alfam, marketed in the U.S. as Lumizyme) was the only ERT approved for Pompe disease treatment in Europe, so the recommendations didn’t include any guidance for switching between ERTs.
In the years since, the ERT Nexviazyme (avalglucosidase alfa) has been approved for LOPD patients in Europe, and Pombiliti (cipaglucosidase alfa), another human-made form of the GAA enzyme that is half of the combo therapy Pombiliti plus Opfolda, is also available. In light of these new treatment options, the consortium reconvened to update its previous recommendations, including for the first time advice for switching amongst ERTs. The team dubbed the new guidelines “triple-S” criteria, since they cover when to start, stop, or switch treatment.
When to start, switch, stop Pompe disease treatment
The new guidelines state that, in order to start ERT, a person must first have a definitive diagnosis of Pompe disease, established via genetic testing and/or enzyme activity testing. The guidelines recommend that ERT should only be started in LOPD patients who have already begun to show signs of disease, meaning muscle weakness and impaired lung function, or muscle MRI showing abnormally high amounts of fat in muscle tissue. Increased fat in muscle tissue is a sign of muscle degeneration and damage.
The guidance notes that, in order to get the full benefits from treatment, ERT is recommended for patients who have some amount of muscle and respiratory activity, and who do not have another life-limiting, co-occurring condition. The recommendations also emphasize that, since ERTs are long-term therapies that are ideally continued indefinitely, both patients and clinicians need to be comfortable with regular treatment and monitoring at least every six months to a year.
According to the new guidelines, there are two situations in which someone with Pompe might consider switching from one ERT to another: if the patient has been on one medication for at least a year without any signs of benefit, or if the patient is experiencing severe infusion reactions when one of the therapies is administered.
The guidelines note that there aren’t enough data to know if patients who are on the older Myozyme might benefit more from switching to a newer treatment. The consortium emphasized that decisions about switching treatments need to be made on a case-by-case basis and should be jointly made by clinicians and patients going over the potential benefits and risks in details.
“Possible switching should … be discussed on a patient-by-patient shared-decision basis,” the authors wrote.
There also are not much data on the use of ERT in Pompe patients who are pregnant or breastfeeding, but the guidelines suggest that ERT may be considered in these cases, considering each individual’s unique situation.
The guidelines suggest that ERT may be discontinued if patients are experiencing severe infusion reactions that can’t be managed with supportive care or switching therapies, if patients develop high levels of anti-ERT antibodies (this can reduce treatment efficacy), or if patients continue to show no signs of benefit after at least two years on ERT treatments. Patient choice is also listed as a valid reason for stopping treatment.
If a patient experiences a notable worsening of disease after discontinuing ERT, the guidelines say that ERT may be restarted. The guidelines emphasized the importance of regular monitoring to track disease severity, both when patients are taking ERT and after they stop or switch treatments.
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