Myozyme may help LOPD patients walk, breathe over long term
Italian study finds treatment safe and effective over 15 years
Long-term use of Myozyme (alglucosidase alfa), marketed as Lumizyme in the U.S., helped individuals with late-onset Pompe disease (LOPD) maintain their ability to walk and breathe, while remaining generally safe and well tolerated over 15 years, according to a study in Italy.
While responses varied, fewer than expected required ventilation and patients lived longer than if the disease had followed its natural course, suggesting long-term benefits from enzyme replacement therapy (ERT).
The study, “Analysis of the Italian cohort of late-onset Pompe disease (LOPD) patients after 10 and 15 years of therapy with alglucosidase alfa,” was published in the Journal of Neurology.
In Pompe disease, mutations in the GAA gene lead to low activity of acid alpha-glucosidase, an enzyme needed to break down a sugar called glycogen. Excess glycogen becomes toxic, particularly to muscle cells, which rely on it for energy. As a result, patients develop progressive muscle weakness and other symptoms.
ERT provides the body with a lab-made version of the enzyme it needs to break down glycogen. While most patients with LOPD — where symptoms begin after 1 year of age — benefit from ERT, responses vary widely, and many show functional decline after 3-5 years.
Researchers reviewed medical records of patients in Italy
To understand how well Sanofi’s Myozyme, an ERT approved for Pompe disease, works and how safe it is after 10 and 15 years of use in children and adults with LOPD, researchers in Italy reviewed the medical records of 85 patients from 15 centers across the country. Motor and respiratory function data were available were available from 85 patients at 10 years and from 42 patients at 15 years after starting ERT.
Age at disease onset ranged from 2 to 61, whereas the mean age at Myozyme start was 43.5 years (range of 7 to 72). The most common symptoms at disease onset were muscle weakness (63%), fatigue (33.3%), muscle cramps or tightness (17.8%), and shortness of breath during physical activity (7.1%).
All patients could walk when they started treatment. The mean distance covered in the six-minute walk test (6MWT), which measures how far someone can walk in six minutes, declined over 15 years in all four functional groups — defined by the patients’ 6MWT score at baseline (study start) — but even the lowest-performing patients at baseline were mostly able to walk 15 years later.
None of those who walked the farthest at the start — a mean of 541 meters (about 1,775 feet) — lost the ability to walk, and the decline found at 10 years was followed by stabilization at 15 years.
The researchers also looked at forced vital capacity (FVC), a measure of how much air someone can exhale after taking a deep breath, with lower percentages indicating worse lung function. Two groups were defined, one with worse lung function (FVC below 80%; group 0) and the other with better lung function (FVC 80% or higher; group 1). Group 0 was stable at 10 years and slightly worsened five years later, whereas group 1 showed a statistically significant decline of FVC% at year 10, followed by stabilization.
Half (50%) of the patients remained off a ventilator at 15 years.
Higher 6MWT at the start of the study correlated with better FVC% at every timepoint, as did better initial FVC% with longer distances in the 6MWT. Male patients and younger individuals exhibited better 6MWT scores.
No patients had to stop Myozyme, and no serious side effects were reported. Five patients died. Results showed risk of death was higher with lower 6MWT scores and in older patients at ERT start.
“The functional, reliable long-term data collected in this study will be useful to compare in the future the results of the new-generation therapies,” the researchers wrote.
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