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).
Read more about therapies for Pompe disease.
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.