Long-term benefits of cipa/mig in late-onset Pompe disease

Cipaglucosidase alfa + miglustat (cipa/mig) was associated with overall maintained improvements or stabilisation of outcomes in patients with late-onset Pompe disease (LOPD) over 104 weeks, compared with alglucosidase alfa + placebo (alg/pbo). The experimental combination therapy was also well-tolerated.

The phase 3 double-blind PROPEL study (NCT03729362) compared cipa/mig with alg/pbo in adults with late-onset Pompe disease (LOPD). Prof. Antonio Toscano (University of Messina, Italy) said that the differences in 6-minute walking distance (6MWD) after 52 weeks did not reach statistical significance [1,2]. However, there were potentially clinically meaningful improvements in motor and respiratory function, as well as biomarkers, which prompted an open-label extension (OLE) trial (NCT04138277). Outcomes included 6MWD, forced vital capacity (FVC), creatine kinase (CK) and hexose tetrasaccharide (Hex4) levels, patient-reported outcomes, and safety. Prof. Toscano reported results after up to 52 weeks on efficacy and safety of cipa/mig [1,3].

Of the 119 participants in the OLE, 82 continued with cipa/mig and 37 switched from alg/pbo to cipa/mig. Of these, 62 and 29 had had enzyme replacement therapy (ERT) before, respectively. Mean change from PROPEL baseline in % predicted 6MWD to week 104 was +3.1 for continuous cipa/mig users and -0.5 for the participants who switched, in the ERT-experienced group, and +8.6 for continuous cipa/mig users and +8.9 for the participants who switched, in the ERT-naïve group. Corresponding numbers for mean change in % predicted FVC were -0.6 and -3.8 in the ERT-experienced group, and -4.8 and -3.1 in ERT-naïve participants. Cipa/mig was associated with a durable reduction in serum CK and urine Hex4 levels by week 104. There were no new safety signals.

Prof. Toscano added that ERT-experienced participants who received cipa/mig in PROPEL showed improvements in patient-reported physical function and fatigue, which remained stable until week 104 [4]. In the alg/pbo group, these scores remained stable until week 52 and deteriorated between weeks 52–104.

1. Toscano A. Cipaglucosidase alfa plus miglustat in adults with late-onset Pompe disease: A phase III open-label extension study. SPS05_2, EAN Congress 2025, 21-24 June 2025, Helsinki, Finland.
2. Schoser B, et al. Lancet Neurol. 2021;20(12):1027-37.
3. Schoser B, et al. J Neurol. 2024;271(5):2810-23.
4. Kishnani PS, et al. J Patient Rep Outcomes. 2024;8(1):132.

Medical writing support was provided by Michiel Tent.

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Posted on 24 June 202524 June 2025