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Introduction <p>No head-to-head studies comparing the efficacy of avalglucosidase alfa (AVA) with cipaglucosidase alfa&#xa0;+&#xa0;miglustat (Cipa+mig) have been conducted in patients with late-onset Pompe disease (LOPD). Two indirect treatment comparisons (ITCs) were conducted to estimate the effects of AVA versus Cipa+mig.</p> Methods <p>ITCs were conducted using simulated treatment comparisons (STCs), adjusting for differences in prognostic factors and treatment effect modifiers. An analysis of patients who were naïve to enzyme replacement therapy (ERT-naive) used anchored STC with individual patient data (IPD) from the Phase 3 COMET (NCT02782741) study of AVA versus alglucosidase alfa (ALG) and aggregate data from patients who were ERT-naïve in the Phase 3 PROPEL (NCT03729362) study of Cipa+mig versus ALG&#xa0;+&#xa0;placebo. For patients who were ERT-experienced, an analysis used unanchored STC with IPD for AVA from the COMET open-label extension, and from NEO-1 (NCT01898364)/NEO-EXT (NCT02032524) studies, and aggregate Cipa+mig data from PROPEL and ATB200-02 (NCT02675465).</p> Results <p>In patients who were ERT-naïve, the difference (95% confidence interval, CI) in mean change from baseline (CFB) at Weeks 49–52 in forced vital capacity percent predicted (FVCpp) showed a numerical improvement for AVA versus Cipa+mig with values of 5.49% (–&#xa0;0.87, 11.86) with mixed model repeated measures analysis (MMRM/MMRM) and 4.69% (−&#xa0;3.22, 12.61) with MMRM/analysis of covariance (ANCOVA). For the 6-min walk test (6MWT), differences were 57.08&#xa0;m (11.04, 103.12) with MMRM/MMRM and 41.88&#xa0;m (−&#xa0;5.46, 89.22) with MMRM/ANCOVA, the former being statistically significant (<i>p</i>&#xa0;&lt;&#xa0;0.02) and the latter numerically in favour of AVA. In patients who were ERT-experienced, at Weeks 48–52 differences for AVA versus Cipa+mig with MMRM/MMRM (CIs/<i>p</i> values unavailable) were 1.40% for FVCpp and 18.85&#xa0;m for 6MWT; with MMRM/Mean CFB, differences of 1.16% (−&#xa0;1.88, 4.19) for FVCpp and 7.67&#xa0;m (−&#xa0;21.67, 37.02) for 6MWT, indicating a numerical improvement in favour of AVA.</p> Conclusions <p>ITCs suggest more favourable respiratory and mobility outcomes with AVA versus Cipa+mig in patients with LOPD, regardless of prior ERT-experience.</p>

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An Indirect Treatment Comparison of Avalglucosidase Alfa versus Cipaglucosidase Alfa Plus Miglustat in Patients with Late-Onset Pompe Disease

  • 期刊论文

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  • 发表日期：

    2025年9月8日

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  • Mark E. Roberts,
  • Irina Proskorovsky,
  • Patricia Guyot,
  • Pragya Shukla,
  • Nathan Thibault,
  • Alaa Hamed,
  • Ruth Pulikottil-Jacob,
  • Lasair O’Callaghan,
  • Laurence Pollissard

摘要

Introduction

No head-to-head studies comparing the efficacy of avalglucosidase alfa (AVA) with cipaglucosidase alfa + miglustat (Cipa+mig) have been conducted in patients with late-onset Pompe disease (LOPD). Two indirect treatment comparisons (ITCs) were conducted to estimate the effects of AVA versus Cipa+mig.

Methods

ITCs were conducted using simulated treatment comparisons (STCs), adjusting for differences in prognostic factors and treatment effect modifiers. An analysis of patients who were naïve to enzyme replacement therapy (ERT-naive) used anchored STC with individual patient data (IPD) from the Phase 3 COMET (NCT02782741) study of AVA versus alglucosidase alfa (ALG) and aggregate data from patients who were ERT-naïve in the Phase 3 PROPEL (NCT03729362) study of Cipa+mig versus ALG + placebo. For patients who were ERT-experienced, an analysis used unanchored STC with IPD for AVA from the COMET open-label extension, and from NEO-1 (NCT01898364)/NEO-EXT (NCT02032524) studies, and aggregate Cipa+mig data from PROPEL and ATB200-02 (NCT02675465).

Results

In patients who were ERT-naïve, the difference (95% confidence interval, CI) in mean change from baseline (CFB) at Weeks 49–52 in forced vital capacity percent predicted (FVCpp) showed a numerical improvement for AVA versus Cipa+mig with values of 5.49% (– 0.87, 11.86) with mixed model repeated measures analysis (MMRM/MMRM) and 4.69% (− 3.22, 12.61) with MMRM/analysis of covariance (ANCOVA). For the 6-min walk test (6MWT), differences were 57.08 m (11.04, 103.12) with MMRM/MMRM and 41.88 m (− 5.46, 89.22) with MMRM/ANCOVA, the former being statistically significant (p < 0.02) and the latter numerically in favour of AVA. In patients who were ERT-experienced, at Weeks 48–52 differences for AVA versus Cipa+mig with MMRM/MMRM (CIs/p values unavailable) were 1.40% for FVCpp and 18.85 m for 6MWT; with MMRM/Mean CFB, differences of 1.16% (− 1.88, 4.19) for FVCpp and 7.67 m (− 21.67, 37.02) for 6MWT, indicating a numerical improvement in favour of AVA.

Conclusions

ITCs suggest more favourable respiratory and mobility outcomes with AVA versus Cipa+mig in patients with LOPD, regardless of prior ERT-experience.