Comparing the efficacy of cipaglucosidase alfa plus miglustat with alglucosidase alfa for late-onset Pompe disease: an expanded network meta-analysis utilizing patient-level and aggregate data
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: Treatment options for late-onset Pompe disease (LOPD) include enzyme replacement therapy (ERT) with alglucosidase alfa (alg), cipaglucosidase alfa plus miglustat (cipa + mig) and avalglucosidase alfa. However, only one randomized controlled trial (RCT) directly compared cipa + mig and alg and had relatively few ERT-naive patients. A multilevel network meta-regression (ML-NMR) integrated individual patient data and aggregate data into indirect treatment comparisons, with relative effects adjusted to any target population, to compare the efficacy of cipa + mig and alg. Materials & methods: A Bayesian ML-NMR was conducted to compare the efficacy of cipa + mig and alg for 6-minute walk distance (6MWD, meters) and percent predicted forced vital capacity (ppFVC) across any target population, using patient-level and aggregate data from RCTs (PROPEL, COMET, LOTS) and phase I/II and open-label extension (OLE) trials (PROPEL OLE, LOTS OLE, COMET OLE, ATB200-02, NEO-1/NEO-EXT), adjusting for baseline covariates. Relative effect estimates were obtained for 6MWD and ppFVC change from baseline to week 52. Two networks were analyzed: network A (RCTs only) and network B (RCTs and single-arm OLE and phase I/II studies matched to comparator arms). To assess the impact of prior ERT exposure, simulations were conducted by only varying ERT duration among included covariates. Results: For cipa + mig compared with alg, both networks were associated with relative increases in 6MWD (mean difference [95% credible interval], Bayesian probability for network A: 13.48 m [6.79, 19.85], >99.9%; network B: 12.59 m [7.89, 17.45], >99.9%) and ppFVC (network A: 1.63% [0.71, 2.60], >99.9%; network B: 3.17% [2.53, 3.81], >99.9%). Network B suggested cipa + mig was favorable (>99.9%) in all groups for both end points and appeared more favorable with increasing ERT duration. Conclusion: Cipa + mig was associated with an improvement in 6MWD and ppFVC relative to alg independent of prior ERT exposure, which appeared more favorable when all available evidence was used. These data could inform decision-making in treating ERT-naive and ERT-experienced patients with LOPD.
Plain language summary
What is this article about?
People with late-onset Pompe disease (LOPD) can lose muscle strength and develop breathing difficulties over time. The first drug used to treat LOPD was alglucosidase alfa (alg); however, people often see worsening health after a few years of treatment with alg. Two newer treatment options have recently been approved: avalglucosidase alfa (aval) and cipaglucosidase alfa plus miglustat (cipa + mig).
This study uses a statistical method to combine data from several different clinical studies into a network to compare how well cipa + mig works compared with alg. This study uses the same method as a previous study comparing cipa + mig with aval.
What were the results?
Outcomes included the distance someone can walk in 6 minutes (6-minute walk distance) and how much air someone can forcefully expel from their lungs (forced vital capacity). Results indicated that, when considering all available evidence, treatment with cipa + mig was associated with an improvement compared with alg, whether the participants had previously been treated with alg or not.
What do the results mean?
Although one clinical trial has tested cipa + mig and alg in adults with LOPD, there was a low number of participants who had not had any treatment before starting that trial. Therefore, a network including all available data supports and strengthens the conclusion that cipa + mig is a more favorable treatment than alg in terms of 6-minute walk distance and forced vital capacity. This favorability is seen in people who have not been treated before and those treated with alg previously.
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© 2026 Amicus Therapeutics. This work is licensed under the Creative Commons Attribution 4.0 License
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Received: 19 October 2025
Accepted: 11 February 2026
Published online: 27 February 2026
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Comparing the efficacy of cipaglucosidase alfa plus miglustat with alglucosidase alfa for late-onset Pompe disease: an expanded network meta-analysis utilizing patient-level and aggregate data. (2026) Journal of Comparative Effectiveness Research. DOI: 10.57264/cer-2025-0174
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