A combination enzyme replacement therapy (ERT), cipaglucosidase alfa/miglustat, demonstrated clinically meaningful motor and respiratory functional improvements in adults with late-onset Pompe disease (LOPD), according to the subgroup analyses of the phase 3 PROPEL trial presented at the World Muscle Society 2021 Virtual Congress.
Patients with LOPD who received cipaglucosidase alfa/miglustat demonstrated an improved 6-Minute Walk Distance (6MWD) test, compared to their baseline distance with the approved standardized ERT of alglucosidase alfa paired with placebo (20.8 ± 4.6 meters vs 7.2 ± 6.6 meters, respectively).
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Throughout the trial, the safety profiles of the 2 different interventions were similar.
Respiratory function, measured by forced vital capacity (FVC), declined more slowly in those taking cipaglucosidase alfa/miglustat, compared with the alglucosidase alfa/placebo group (-0.9 ± 0.7% vs -4.0 ± 0.8%), with a nominal statistically significant difference (P =.023). However, the difference failed to reach statistical superiority (P =.071).
In the study, researchers randomized 123 participants into 2 groups, with 85 in the cipaglucosidase group and 38 in the alglucosidase group. Of these participants, 80 completed the study in the cipaglucosidase group and 37 in the alglucosidase group.
Participants in the cipaglucosidase alfa group received 20 mg/kg of the drug plus 260 mg miglustat every 2 weeks, and participants in the alglucosidase alfa group received 20 mg/kg of the drug plus a placebo every 2 weeks.
Investigators analyzed the efficacy of these 2 treatments in 2 different subgroups: ERT-experienced vs ERT-naïve participants, and participants with specific baseline parameters: <300 or ≥300 meters on the 6MWD or <55% or ≥55% FVC. Three participants each had a baseline of <300 meters for the 6MWD and <55% for the FVC test. Analyses could not accurately be performed on these subgroups due to these small numbers.
Participants who previously had ERT demonstrated a statistical difference in both the 6MWD and the FVC (P <.05) tests when taking cipaglucosidase alfa/miglustat. In the ERT-naïve population, alglucosidase alfa/placebo demonstrated better results in both the 6MWD and FVC; however, they were not statistically significant.
Regardless of which drug they received, ERT-naïve participants with baselines ≥300 meters on the 6MWD demonstrated similar improvements, and participants with ≥55% on the FVC demonstrated similar declines.
Schoser B, Bratkovic D, Byrne B, et al. Cipaglucosidase alfa/miglustat versus alglucosidase alfa/placebo in Late-onset Pompe disease: PROPEL study subgroup analyses. Poster presented at: World Muscle Society 2021; September 20-24, 2021; Virtual.