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

IF 4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-09-08 DOI:10.1007/s12325-025-03301-9

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

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引用次数: 0

Abstract

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.

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阿伐葡萄糖苷酶与西葡葡萄糖苷酶加米卢司他对迟发性庞贝病的间接治疗比较

目前还没有比较avalglucosidase alfa （AVA）和Cipa+ miglustat （Cipa+mig）治疗迟发性Pompe病（LOPD）疗效的研究。进行了两项间接治疗比较（ITCs）来评估AVA与Cipa+mig的效果。方法：采用模拟治疗比较（STCs）进行ITCs，调整预后因素和治疗效果调节剂的差异。一项针对naïve接受酶替代治疗（ERT-naive）的患者的分析使用锚定STC和来自AVA与ALG （ALG）的3期COMET （NCT02782741）研究的个体患者数据（IPD），以及来自Cipa+mig与ALG +安慰剂的3期PROPEL （NCT03729362）研究的ERT-naïve患者的汇总数据。对于有ert经验的患者，分析使用来自COMET开放标签扩展和NEO-1 (NCT01898364)/NEO-EXT （NCT02032524）研究的无锚定STC + IPD治疗AVA，并汇总来自PROPEL和ATB200-02 （NCT02675465）的Cipa+mig数据。结果：在ERT-naïve患者中，第49-52周强迫肺活量预测百分比（FVCpp）的平均基线变化（CFB）的差异（95%置信区间，CI）显示AVA与Cipa+mig的数值改善，混合模型重复测量分析（MMRM/MMRM）的值为5.49% (- 0.87,11.86)，MMRM/协方差分析（ANCOVA）的值为4.69%（- 3.22,12.61）。对于6分钟步行测试（6MWT）， MMRM/MMRM的差异为57.08 m (11.04, 103.12)， MMRM/ANCOVA的差异为41.88 m(- 5.46, 89.22)，前者具有统计学意义(p)。结论：ITCs表明，在LOPD患者中，AVA比Cipa+mig更有利的呼吸和活动结果，与先前的ert经验无关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.