Cipaglucosidase alfa plus miglustat is not better than alglucosidase alfa plus placebo in improving the 6-minute walking distance in patients with late-onset Pompe disease. This is according to the results of a phase 3 clinical trial that compared the safety and efficacy of the 2 treatment approaches.

Pompe disease is characterized by the deficiency of the enzyme α-glucosidase. Enzyme replacement therapy—where the missing enzyme is provided to the body from outside—is the only treatment approved by the US Food and Drug Administration (FDA).

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However, some patients do not respond to this therapy. The present clinical trial aimed to investigate whether adding an enzyme stabilizer, miglustat, to a novel recombinant human acid α-glucosidase enzyme, cipaglucosidase alfa, could increase the efficacy of enzyme replacement therapy.

The double-blind, parallel-group study enrolled 125 patients with late-onset Pompe disease, aged at least 18 years, who either never received enzyme replacement therapy or received alglucosidase alfa for at least 2 years. Of these, 85 received 20 mg/kg of intravenous cipaglucosidase alfa plus miglustat and 40 received 20 mg/kg of intravenous alglucosidase alfa plus placebo once every 2 weeks for 52 weeks.

At the end of the treatment period, the change in the 6-minute walk distance from baseline was 20.8 m in the cipaglucosidase alfa plus miglustat group. It was 7.2 m in the alglucosidase alfa plus placebo group. However, there were no statistically significant improvements.

The incidence of adverse events due to treatment was similar between the 2 groups and included falls, headache, nasopharyngitis, myalgia, and arthralgia.

“Further studies should investigate the longer-term safety and efficacy of cipaglucosidase alfa plus miglustat and whether this investigational two-component therapy might provide benefits, particularly in respiratory function and in patients who have been receiving enzyme replacement therapy for more than 2 years,” wrote the authors of the study, which was published in The Lancet Neurology.


Schoser B, Roberts M, Byrne BJ; PROPEL Study Group. Safety and efficacy of cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo in late-onset Pompe disease (PROPEL): an international, randomised, double-blind, parallel-group, phase 3 trial. Lancet Neurol. 2021;20(12):1027-1037. doi:10.1016/S1474-4422(21)00331-8

PROPEL study – a study comparing ATB200/AT2221 with alglucosidase/placebo in adult subjects with LOPD. US National Library of Medicine. Last updated October 13, 2021. Accessed December 8, 2021.