ERT doesn’t entirely ease disease burden for Pompe patients
Alternative therapies, more newborn screening could help, researchers say
Pompe disease patients bear a substantial burden from coexisting conditions and the ongoing need for supportive care, despite treatment with enzyme replacement therapy (ERT), a real-world study in the U.S. found.
Researchers also found a relatively high rate of ERT discontinuation, particularly among people with late-onset Pompe disease (LOPD). Nearly one-third of LOPD patients stopped treatment within two years of starting it.
The findings “highlight the need for alternative therapies to support patients with Pompe disease and reduce their burden,” researchers wrote. They added that newborn screening — allowing for earlier diagnosis and treatment — may help reduce the disease burden in infantile-onset Pompe disease (IOPD).
The study, “A retrospective cohort study describing the disease burden in patients with Pompe disease treated with enzyme replacement therapy in the United States,” was published in the Journal of Neuromuscular Diseases.
Pompe disease is caused by mutations that lead to a missing or dysfunctional GAA enzyme, which is needed to break down a complex sugar molecule called glycogen. When there is not enough functional GAA available, glycogen accumulates inside cells, particularly in muscle cells, leading to Pompe symptoms such as muscle weakness, eating difficulties, hearing problems, and breathing issues.
A treatment, not a cure
ERT, the standard treatment for Pompe disease, is designed to deliver a lab-made version of the GAA enzyme to patients, helping to replace the missing or nonfunctional enzyme. This has meaningfully improved outcomes for patients, but ERT cannot cure the disease, and many people still experience a substantial disease burden.
Because the real-world burden of Pompe disease among people treated with ERT remains poorly studied, the researchers set out to examine how patients in the U.S. are doing in everyday clinical settings.
The team analyzed insurance claims data from 105 patients, 50 of whom had IOPD and 55 who had LOPD. Patients were identified through the MarketScan research databases, which contain inpatient, outpatient, and prescription drug information from more than 270 million people in the U.S.
The study looked at patients who had available claims from March 2012 through August 2022. The average age at diagnosis was 4 months for those with IOPD and 32.2 years for those with LOPD. About 60% of patients were male.
Respiratory complications were the most common coexisting condition, affecting 79% to 85% of patients in the first year after ERT initiation. Problems related to mobility and motor milestones (54%-57%) and gastrointestinal dysfunction (33%-68%), including swallowing difficulties, were also frequent.
Except for cardiovascular issues (17%–29%), all of these comorbidities were more common in infants and children with IOPD than in LOPD patients.
Supportive care was heavily used, particularly in the IOPD group. Physical therapy, speech therapy, nutritional therapy, and occupational therapy were all substantially more common in IOPD than in LOPD, while respiratory and mobility support were used at similar rates in both groups.
Nearly half of IOPD patients received immune tolerance induction or intravenous immunoglobulin treatments, which aim to reduce the risk of developing inhibitor antibodies that may render ERT less effective. Some 1.8% of LOPD patients used those approaches.
Overall, 83.8% of participants were treated with Lumizyme (alglucosidase alfa), the only approved ERT for IOPD. Dosing every two weeks was most common, but some patients, mainly in the IOPD group, received weekly dosing.
Median treatment duration was 8.2 years for IOPD patients and 4.1 years for LOPD. This was likely due in part to greater rates of ERT discontinuation among those with LOPD. After one year, 10.3% of people with IOPD and 11.7% of those with LOPD had stopped ERT. After two years, discontinuation rose to 14.1% in the IOPD group and 32% in the LOPD group.
“This real-world analysis showed that patients with Pompe disease in the United States experience a substantial disease burden despite treatment with standard-of-care ERT, with high rates of comorbidities, utilization of supportive services, and concomitant medications,” the researchers wrote. “Our findings highlight the need for alternative therapies to support patients with Pompe disease and reduce their burden.”
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