Long-term Lumizyme slows lung function decline in LOPD
Patients with poor function before treatment saw the most early gains
Treatment with Lumizyme (alglucosidase alfa) improved lung function in the short term and slowed lung function decline over the long term among people with late-onset Pompe disease (LOPD), according to a 13-year, real-world analysis.
Patients with poor lung function before treatment saw the greatest early gains, while those with good initial lung function remained stable for up to five years. After six months, however, lung function slowly declined in many patients, particularly those with more than five years of treatment.
Still, the decline in lung function in LOPD patients who received long-term treatment was slower than in untreated Pompe patients, the researchers said in “Changes in forced vital capacity over ≤ 13 years among patients with late-onset Pompe disease treated with alglucosidase alfa: new modeling of real-world data from the Pompe Registry,” in the Journal of Neurology.
In Pompe disease, the enzyme acid alpha-glucosidase (GAA) is defective or missing. Without GAA, glycogen, the stored form of glucose, builds up to toxic levels in body tissues, especially muscles.
Lumizyme, sold under the name Myozyme in the European Union, is an enzyme replacement therapy that provides Pompe patients with a lab-made source of GAA. It’s approved for all types of Pompe, including LOPD, when symptoms develop after the first year of life through adulthood.
Nearly all LOPD patients have progressive weakness in their proximal muscles, which are those closer to the trunk of the body, which can interfere with breathing.
A previous real-world study suggested Lumizyme treatment over five years preserved lung function for LOPD patients. Early treatment was most beneficial, particularly among those with better breathing at the time treatment started.
Long-term treatment with Lumizyme
Here, an international team investigated the real-world impact of Lumizyme on breathing for up to 13 years in people with LOPD. Sanofi, Lumizyme’s developer, funded the study. Data were sourced from the Sanofi-sponsored Pompe Registry (NCT00231400), which collects clinical data about identifying Pompe disease, its onset, progression, and treatment course.
The study enrolled 485 patients with at least five years of Lumizyme treatment, of whom 50 (10.3%) were children or adolescents, ages 5-17. Before treatment, about one in four (27.9%) needed noninvasive breathing support.
Lung function was assessed by percent predicted forced vital capacity (FVC), the total amount of air that can be forcibly exhaled in a breath. It compared the patient’s FVC to the average of the normal FVC for a person of the same sex, height, and age. Younger patients here had a higher median FVC than adults (80.4% vs. 65.5%).
FVC increased during the first six months on Lumizyme, at a rate of 1.83% per year. After that, the FVC rate significantly declined by 0.54% annually from six months to five years and fell by 1% each year from five to 13 years. These different rates of decline weren’t statistically different, however.
The decline in FVC rates after six months of treatment was slower than published natural history rates, which show declines between 1% and 4.6% per year.
The most significant breathing improvements were seen in those with poor initial lung function, or an FVC of less than 55% at baseline, that is, the study’s start. In these patients, FVC significantly increased over the first year and then slowly, but nonsignificantly, declined.
Compared to the FVC decline in untreated Pompe disease, “these benefits in the patients severely impaired at baseline persisted over the ensuing 13 years,” the researchers wrote.
In those patients with moderate lung function at baseline, or an FVC between 55 and 80%, breathing remained stable for a year, then declined by 1% per year up to year 13. In patients with good lung function at baseline, or an FVC greater than 80%, breathing remained relatively stable until year five, then declined by 1.5% per year up to year 13.
“Patients with baseline respiratory function in the normal range … had a long five-year period of stability following treatment initiation,” the researchers said. “Conservation of their existing respiratory function was observed for several years thereafter.”
Individually, nearly all the patients (96.1%) showed improved or stable lung function during the first six months on Lumizyme. After that, about seven in 10 patients (69.7%) saw a decrease in lung function from six months to five years and most (86.8%) saw declines beyond five years.
“This analysis of long-term real-world FVC data demonstrates a benefit of [Lumizyme] on respiratory function, which is durable and clinically meaningful in comparison with published data on the untreated natural course of LOPD,” the researchers wrote. “Nevertheless, an unmet need persists since most individuals demonstrate a decline in lung function five years after initiating treatment, which may be addressed by future therapies.”
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