Switching therapies may stabilize walking decline in late-onset Pompe
Motor function stabilized after adults moved from Myozyme to Nexviadyme
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Switching to Nexviadyme (avalglucosidase alfa) may help stabilize declining walking ability in adults with late-onset Pompe disease whose symptoms worsen despite treatment with Myozyme (alglucosidase alfa), according to a real-world study from France.
Researchers found that the group’s decline in walking ability halted during the first year after switching and remained stable in the second year among the 29 patients with two-year follow-up. Lung function remained largely unchanged after the switch.
Study finds walking decline stabilized after treatment switch
“For patients experiencing significant walking decline under [Myozyme] therapy, switching to [Nexviadyme] resulted in disease stabilization,” the researchers wrote.
The study, “Real-Life Effectiveness After Switching to Avalglucosidase Alfa in Late-Onset Pompe Disease Patients Worsening on Alglucosidase Alfa Therapy: A French Cohort Study,” was published in the European Journal of Neurology.
Pompe disease is caused by genetic mutations that result in too little functional acid alpha-glucosidase (GAA), an enzyme that normally breaks down a complex sugar molecule called glycogen. As a result, glycogen builds up to harmful levels in body tissues, especially muscles. Over time, the disease leads to progressive muscle weakness, difficulty walking, and breathing problems. LOPD typically begins after age 1.
Myozyme, sold as Lumizyme in the U.S., is an enzyme replacement treatment (ERT) for all types of Pompe disease. It supplies the body with a functional version of the GAA enzyme, helping clear glycogen from cells. While the therapy can slow or stabilize disease progression in people with LOPD, many eventually begin to lose some of its benefits after several years of treatment.
Nexviadyme, sold as Nexviazyme in the U.S., is a next-generation ERT designed to improve the uptake of GAA into muscle cells. It was approved in the U.S. in 2021 for people age 1 year and older with LOPD. In Europe, it was approved the following year for treating both late-onset and infantile-onset Pompe disease. Both Myozyme and Nexviadyme are marketed by Sanofi.
French access programs allowed earlier use of Nexviadyme
In France, Nexviadyme first became available through a compassionate use program in 2020 for people with LOPD whose disease continued to worsen despite treatment with Myozyme, allowing eligible patients to receive the therapy before it was formally approved. Access was later extended through an early access program beginning in 2022.
To evaluate how patients fared after switching therapies in routine clinical practice, researchers analyzed data from 47 adults with LOPD enrolled in the French Pompe Registry. All had switched from Myozyme to Nexviadyme because their symptoms continued to worsen despite treatment.
Participants had a mean age of 43 years at diagnosis and had experienced symptoms for a mean of 10 years before being diagnosed. Before switching, they had been treated with Myozyme for a mean of 10 years. Twenty-nine participants were followed for two years after the switch.
Before switching to Nexviadyme, participants were losing a mean of 27 meters (about 89 feet) per year on the six-minute walk test, a standard measure of walking ability. During the first year after switching, they instead gained a mean of 17 meters (about 56 feet). In the second year, they lost a mean of 10 meters (about 33 feet), a change that was not statistically significant, suggesting that the previous decline had stabilized.
Response varied across patients after the switch
Not all patients responded equally, however. Twenty met the study’s definition of a good motor response, based on improved walking ability after switching, while three continued to worsen. In exploratory analyses, better responses were associated with younger age, shorter disease duration, higher body mass index — a measure based on height and weight — and a steeper decline in walking ability before the switch.
Lung function remained stable after the switch. Participants lost a mean of 62 mL in forced vital capacity (FVC), a measure of the maximum amount of air a person can forcefully exhale after taking a deep breath, during the year before switching. After switching treatments, the mean decline was 13 mL in the first year and 22 mL in the second year. However, these differences were not statistically significant.
According to the investigators, the lack of significant change in lung function may partly be explained by the fact that patients were generally switched because of motor rather than respiratory decline.
“We have demonstrated in this real-life study that patients suffering from LOPD on prior [Myozyme], having been switched to [Nexviadyme] because of respiratory and/or motor worsening, present a significant stabilization of the motor decline, sustained at 2 years,” the researchers concluded. “On the respiratory level, no significant change was observed after 1 or 2 years since the switch.”
“Longer follow-up assessments over several years, ideally including data from other countries, will be needed in order to draw conclusions in larger [patients’ groups],” they added.
The study was supported by Sanofi, Amicus Therapeutics, and Astellas Pharma Europe. Several researchers reported financial or other relationships with Sanofi and other pharmaceutical companies.
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