Treatment with Myozyme (alglucosidase alfa, marketed as Lumizyme in the U.S.) improves walking ability and may stabilize respiratory function in adults with Pompe disease during the first three years of treatment, according to a recent study.
However, factors such as aging may explain the loss of benefits observed at later stages.
The study, “Long‐term benefit of enzyme replacement therapy with alglucosidase alfa in adults with Pompe disease: prospective analysis from the French Pompe Registry,” was published in the Journal of Inherited Metabolic Disease.
Enzyme replacement therapy (ERT) for Pompe disease is intended to replace the missing or defective alpha-glucosidase. This enzyme converts glycogen into the simpler sugar glucose, which the body uses as a source of energy. The buildup of glycogen in liver and muscle cells cause progressive symptoms, such as muscular weakness, as well as cardiac and respiratory complications.
Improving the ability to walk and respiratory function are key goals in the treatment of Pompe. Although ERT with Sanofi Genzyme‘s Myozyme has demonstrated improvement in walking distance and respiratory tests in all forms of the disease, few studies have evaluated the therapy’s long-term effectiveness.
Researchers in France used data from the national Pompe Registry to assess the long-term clinical effects of Myozyme, the only available ERT for Pompe. They identified records of 158 patients (48.1% men, 51.9% women) receiving Myozyme, and 39 patients who were not receiving ERT for a variety of reasons that included advanced age, mild disease and refusal to accept the constraints and potential allergic risks of ERT. As untreated patients showed significantly less motor and respiratory impairments, they could not be used as controls.
Age at disease onset varied from 10 to 69, while age at study inclusion ranged from 18 to 84. Disease duration ranged between zero and 59 years. The median length of follow-up was 5.34 years.
Patients receiving Myozyme showed improvements on the 6-minute walking test (6MWT) and Motor Function Measurement test, two standard assessments, during the first three years of treatment. However, following this initial increase in walking distance, patients underwent a progressive decline. A cut-off point to the start of clinical worsening was found at 2.2 years in the 6MWT, where a 1.4% improvement per year was followed by a 2.3% annual decline.
According to the scientists, several factors may help explain this loss of therapeutic benefit, including age-related complications such as osteoporosis, variable responses to therapy by muscle type and differing levels of glycogen between patients.
Overall, functional tests of walking and climbing stairs over six years on Myozyme show stabilized disability, the investigators said.
Although the researchers observed a slight increase in patients needing non-invasive ventilation after three years on Myozyme, other measures of respiratory function — such as the difference from sitting to supine positions in forced vital capacity (FVC), and maximal expiratory pressure (the maximal effort of respiratory muscles) — remained stable throughout the study period, suggesting that ERT stabilizes respiratory function among adults with Pompe.
Overall, men showed a better initial response to Myozyme than women, although both showed similar rates of decline later in treatment. Patients with higher initial 6MWT and FVC values showed stronger improvements in walking test scores than participants with lower starting scores.
Higher starting FVC values were associated with steeper respiratory function decline.
Twenty-six participants discontinued treatment during the study. Fifteen patients died, but none due to Myozyme-related effects. Fourteen patients reported allergy symptoms, but only two cases involved anaphylactic shock.
In summary, “this study provides further evidence that ERT improves walking abilities and likely stabilizes respiratory function in adult patients with Pompe disease, with a ceiling effect for the 6MWT in the first 3 years of treatment,” the scientists wrote.
“These results also highlight the importance of registries to collect clinical data prospectively, allowing evaluation of long-term effect or treatments in rare diseases,” they added.
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