Switching to Pombiliti + Opfolda boosts mobility, breathing in LOPD
Researchers analyzed new data from Phase 3 PROPEL study
Switching from Lumizyme (alglucosidase alfa) to Pombiliti + Opfolda (cipaglucosidase alfa and miglustat) improved or stabilized motor function, muscle strength, and lung function in adults with late-onset Pompe disease (LOPD).
That’s according to a new analysis from the Phase 3 PROPEL trial (NCT03729362) that also showed that those who remained on Lumizyme remained stable or worsened on most outcomes.
“Given that LOPD is a progressive condition, it’s imperative that physicians assess when patients should consider switching to Pombiliti + Opfolda,” Hani A. Kushlaf, MD, the study’s lead author and a professor of neurology and pathology at the University of Cincinnati in Ohio, said in a press release.
The analysis was described in the study, “Switching Enzyme Replacement Therapy for Late-Onset Pompe Disease From Alglucosidase Alfa to Cipaglucosidase Alfa Plus Miglustat: Post Hoc Effect Size Analysis of PROPEL,” and published in Muscle & Nerve. The work was funded by Amicus Therapeutics, which markets Pombiliti + Opfolda. Four study authors are employees at Amicus.
In Pompe, the enzyme acid alpha-glucosidase (GAA) is defective or missing, meaning the complex sugar glycogen that’s stored in muscles can’t be broken down. The buildup of glycogen causes muscle damage and various symptoms, including progressive muscle weakness, poor muscle tone, breathing problems, and an enlarged heart.
What is Pombiliti + Opfolda?
Pombiliti + Opfolda contains cipaglucosidase alfa, a lab-made form of the missing GAA enzyme, plus a small stabilizing molecule (miglustat). It’s approved in the U.S. and elsewhere for adults with LOPD to enhance walking and improve or stabilize lung function.
The PROPEL trial, which enrolled 123 adults with LOPD who could walk, compared the safety and efficacy of Pombiliti + Opfolda against Lumizyme, the first approved enzyme replacement therapy, or ERT, for Pompe disease. Before the study, about three-quarters of the participants had been on Lumizyme.
Pombiliti + Opfolda outperformed Lumizyme at helping patients with LOPD walk farther after a year. Still, the difference was statistically significant only in the subset of patients who’d previously received Lumizyme. The combination therapy also slowed lung function decline.
Here, researchers analyzed PROPEL data to assess the within-group effect sizes, or the treatment outcomes of 65 patients who switched from Lumizyme to Pombiliti + Opfolda and 30 who remained on Lumizyme. All had previously received Lumizyme for a median of 7.4 years.
“A standardized effect size analysis provides a way to assess treatment responses across multiple study endpoints and is informative for conditions with a range of symptoms, such as LOPD,” the researchers wrote.
Improved motor, lung function
According to the analysis, motor function significantly improved in those who switched to Pombiliti + Opfolda, as demonstrated by increases in the distance walked in six minutes. Those who remained on Lumizyme showed no such improvements and motor function worsened in some cases.
Significant enhancements in lower and upper extremity muscle strength, and overall, were also seen in the Pombiliti + Opfolda group, as assessed by the manual muscle test. Effects on muscle strength scores with Lumizyme were generally smaller and didn’t reach significance. Still, total scores on the quantitative muscle test, a more comprehensive measure, indicated stabilization of muscle strength in both groups.
Switching to Pombiliti + Opfolda stabilized lung function, as demonstrated by five of six measures. In this group, however, there was a non-significant worsening in slow vital capacity while sitting, the amount of air exhaled slowly and completely after a deep breath. In the Lumizyme group, four assessments showed a significant worsening.
Other improvements with Pombiliti + Opfolda over Lumizyme
In patient-reported outcomes, the Pombiliti + Opfolda group saw significant gains in several Subject Global Impression of Change (SGIC) domains, including muscle function, ability to move around, activities of daily living, physical well-being, and energy. Effect sizes for SGIC domains in the Lumizyme group suggested stability.
When SGIC domain scores from the two groups were compared, there was a higher percentage of patients who saw improvements and a lower percentage who reported worsening in SGIC domains with Pombiliti + Opfolda than with Lumizyme.
Pombiliti + Opfolda also significantly eased fatigue, as shown by the PROMIS-Fatigue test, while Lumizyme significantly reduced shortness of breath using the PROMIS-Dyspnea test. The Physician Global Impression of Change scores showed significant gains with Pombiliti + Opfolda and stability with Lumizyme.
Lastly, biomarker data showed significant improvements with Pombiliti + Opfolda for creatine kinase, a marker of muscle damage, and Hex4 for glycogen storage. The biomarkers significantly worsened with Lumizyme.
“Across the different domains in this analysis, patients who switched to Pombiliti + Opfolda experienced stability or improvement on many measures … compared to those who remained on [Lumizyme], who primarily stayed stable or experienced worsening,” Kushlaf said.
In a safety assessment, Pombiliti + Opfolda was generally well tolerated, with a safety profile similar to the Lumizyme group. One serious adverse event of anaphylaxis, a severe immune reaction, occurred in the Pombiliti + Opfolda group and was deemed possibly treatment-related.
“We view these results as further validation of the differentiated mechanism and clinical profile of Pombiliti + Opfolda and remain committed to advancing therapies that make a tangible difference in the lives of people living with late-onset Pompe disease,” said Jeff Castelli, PhD, chief development officer at Amicus.
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