Cipaglucosidase alfa/miglustat treatment showed clinically meaningful improvements in motor and respiratory functions compared to approved enzyme replacement therapy (ERT) in patients with late-onset Pompe disease (LOPD), according to a subgroup analysis of the PROPEL clinical trial.

PROPEL was a phase 3, double-blind, randomized study to assess the safety and efficacy of intravenous cipaglucosidase alfa coadministered with oral miglustat compared to alglucosidase alfa plus placebo. Cipaglucosidase alfa is a novel recombinant human GAA enzyme and miglustat is an enzyme stabilizer.

The trial recruited 123 participants aged 18 years and older with LOPD at 62 sites across the world and was completed on January 15, 2021. Some of the patients were previously treated with ERT while others were treatment-naive.


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The subgroup analysis compared patients with a 6-Minute Walk Distance score of fewer than 300 m vs 300 m or more at baseline and a percent predicted forced vital capacity (a measure of lung function) of less than 55% vs 55% or more at baseline.

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The results showed that at week 52, there was a 14 m increase in the 6-Minute Walk Distance on average in patients treated with cipaglucosidase alfa plus miglustat compared to those treated with alglucosidase alfa and placebo. However, this increase was not statistically significant.

In terms of percent predicted forced vital capacity, there was a 3% improvement in patients treated with cipaglucosidase alfa plus miglustat compared to those treated with approved ERT plus placebo. This was statistically significant even though just nominally and also clinically meaningful.

Clinically significant improvements were noted with cipaglucosidase alfa plus miglustat in patients who had previously been treated with ERT both in terms of 6-Minute Walk Distance scores and percent predicted forced vital capacities. 

Outcomes consistently favored cipaglucosidase alfa/miglustat treatment in all subgroups regardless of the 6-Minute Walk Distance and percent predicted forced vital capacity at baseline. 

References

Byrne B, Bratkovic D, Díaz-Manera J, et al. Cipaglucosidase alfa/miglustat versus alglucosidase alfa/placebo in late-onset Pompe disease (LOPD): PROPEL study subgroup analyses. Mol Genet Metab. 2022;135(2):S27-S28. doi:10.1016/j.ymgme.2021.11.054

PROPEL study – A study comparing ATB200/AT2221 with alglucosidase/placebo in adult subjects with LOPD. US National Library of Medicine. Updated October 13, 2021. Accessed February 23, 2022.