Combination therapy tops Nexviazyme for LOPD: Study
Pombiliti plus Opfolda may improve walking, breathing
Combination therapy Pombiliti plus Opfolda (cipaglucosidase alfa/miglustat) may help people with late-onset Pompe disease (LOPD) walk farther and breathe better compared with Nexviazyme (avalglucosidase alfa), particularly if they’ve been on enzyme replacement therapy for longer, according to a meta-analysis of clinical trials and real-world data.
The study, “Comparing the efficacy of cipaglucosidase alfa plus miglustat with other enzyme replacement therapies for late-onset Pompe disease: a network meta-analysis utilizing patient-level and aggregate data,” was published in the Journal of Comparative Effectiveness Research. The study was supported by Amicus Therapeutics, which markets Pombiliti plus Opfolda. Some study authors are employees of the company.
Pompe disease occurs when not enough of an enzyme called acid alpha-glucosidase (GAA) is available to break down glycogen, a complex sugar. When glycogen builds up, it can be toxic, particularly to muscle cells, which store that sugar molecule as an energy reserve.
Enzyme replacement therapy (ERT) can ease symptoms of Pompe disease by providing the body with the missing enzyme. Compared with Lumizyme (alglucosidase alfa), the first ERT approved for Pompe disease, second-generation Nexviazyme (from Sanofi) and Pombiliti plus Opfolda, a combination of an ERT called cipaglucosidase alfa with a stabilizer called miglustat, may bring additional benefits.
Which one works best for people with LOPD, a form of the disease in which symptoms arise during childhood or later, is unclear. Because there aren’t any head-to-head clinical trials available, an international team of researchers made an indirect comparison based on data from previous studies. “This comparison may help us to better understand whether eligible patients with LOPD may benefit from one or another treatment, and potentially inform health technology assessment, cost effectiveness and reimbursement decisions,” the researchers wrote.
Walking farther, breathing better
A search of the literature identified 33 records from six studies, none of which compared the two treatments directly. These included two randomized, controlled trials — PROPEL (NCT03729362) and COMET (NCT02782741) — in which participants are randomly assigned to different groups, and two single-arm (only one experimental group) Phase 1/2 clinical trials. The other two were open-label extension studies that reflected the real-world settings for people with LOPD.
An analysis of all available data showed that patients on Pombiliti plus Opfolda walked an average of 28.93 meters (about 95 feet) farther than patients on Nexviazyme during a six-minute walk test, a measure of the maximum distance a person can cover in six minutes.
Their lung function, measured by the forced vital capacity, improved by an average of 2.88 percentage points compared with patients on Nexviazyme. Forced vital capacity measures the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible.
The benefits of Pombiliti plus Opfolda increased the longer patients had been on previous ERT. “For patients who have been undergoing therapy for an extended period of time, [Pombiliti plus Opfolda] may be able to clear accumulated, and more highly complexed, glycogen in skeletal muscles,” the researchers wrote.
When only the randomized controlled trials were considered, the results favored Nexviazyme. In this analysis, patients on Pombiliti plus Opfolda walked an average of 10.02 meters (about 33 feet) less and had an average decrease of 1.45 percentage points in forced vital capacity compared with those on Nexviazyme.
However, the two randomized controlled trials differed greatly in the proportion of patients who’d been on previous ERT (77% in the PROPEL trial vs. 0% in COMET). Therefore, “research should continue as new evidence on [Pombiliti plus Opfolda] and [Nexviazyme] for LOPD continues to evolve in the real-world setting,” the team wrote.
For the moment, this meta-analysis provides “clinically important results and inform decision-making on the optimal choice of treatment in patients with LOPD, with [Pombiliti plus Opfolda] being the treatment option with the highest probability of ranking best among all treatments compared when all available evidence was used,” the researchers wrote.
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