Schoser Benedikt, Kishnani Priya S, Bratkovic Drago, Byrne Barry J, Claeys Kristl G, Díaz-Manera Jordi, Laforêt Pascal, Roberts Mark, Toscano Antonio, van der Ploeg Ans T, Castelli Jeff, Goldman Mitchell, Holdbrook Fred, Sitaraman Das Sheela, Wasfi Yasmine, Mozaffar Tahseen
Friedrich-Baur-Institute at the Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany.
Duke University Medical Center, Durham, NC, USA.
J Neurol. 2024 May;271(5):2810-2823. doi: 10.1007/s00415-024-12236-0. Epub 2024 Feb 28.
The phase III double-blind PROPEL study compared the novel two-component therapy cipaglucosidase alfa + miglustat (cipa + mig) with alglucosidase alfa + placebo (alg + pbo) in adults with late-onset Pompe disease (LOPD). This ongoing open-label extension (OLE; NCT04138277) evaluates long-term safety and efficacy of cipa + mig. Outcomes include 6-min walk distance (6MWD), forced vital capacity (FVC), creatine kinase (CK) and hexose tetrasaccharide (Hex4) levels, patient-reported outcomes and safety. Data are reported as change from PROPEL baseline to OLE week 52 (104 weeks post-PROPEL baseline). Of 118 patients treated in the OLE, 81 continued cipa + mig treatment from PROPEL (cipa + mig group; 61 enzyme replacement therapy [ERT] experienced prior to PROPEL; 20 ERT naïve) and 37 switched from alg + pbo to cipa + mig (switch group; 29 ERT experienced; 8 ERT naive). Mean (standard deviation [SD]) change in % predicted 6MWD from baseline to week 104 was + 3.1 (8.1) for cipa + mig and - 0.5 (7.8) for the ERT-experienced switch group, and + 8.6 (8.6) for cipa + mig and + 8.9 (11.7) for the ERT-naïve switch group. Mean (SD) change in % predicted FVC was - 0.6 (7.5) for cipa + mig and - 3.8 (6.2) for the ERT-experienced switch group, and - 4.8 (6.5) and - 3.1 (6.7), respectively, in ERT-naïve patients. CK and Hex4 levels improved in both treatment groups by week 104 with cipa + mig treatment. Three patients discontinued the OLE due to infusion-associated reactions. No new safety signals were identified. Cipa + mig treatment up to 104 weeks was associated with overall maintained improvements (6MWD, biomarkers) or stabilization (FVC) from baseline with continued durability, and was well tolerated, supporting long-term benefits for patients with LOPD.Trial registration number: NCT04138277; trial start date: December 18, 2019.
III期双盲PROPEL研究比较了新型双组分疗法西帕糖苷酶α+米格鲁司他（cipa+mig）与阿糖苷酶α+安慰剂（alg+pbo）在晚发型庞贝病（LOPD）成人患者中的疗效。这项正在进行的开放标签扩展研究（OLE；NCT04138277）评估了cipa+mig的长期安全性和有效性。观察指标包括6分钟步行距离（6MWD）、用力肺活量（FVC）、肌酸激酶（CK）和四糖己糖（Hex4）水平、患者报告的结局以及安全性。数据报告为从PROPEL基线到OLE第52周（PROPEL基线后104周）的变化。在OLE研究中接受治疗的118例患者中，81例从PROPEL研究开始继续接受cipa+mig治疗（cipa+mig组；61例在PROPEL研究之前接受过酶替代疗法[ERT]；20例未接受过ERT），37例从alg+pbo转换为cipa+mig（转换组；29例接受过ERT；8例未接受过ERT）。从基线到第104周，cipa+mig组预测6MWD的平均（标准差[SD]）变化为+3.1（8.1），接受过ERT的转换组为-0.5（7.8），cipa+mig组中未接受过ERT的转换组为+8.6（8.6），接受过ERT的转换组为+8.9（11.7）。cipa+mig组预测FVC的平均（SD）变化为-0.6（7.5），接受过ERT的转换组为-3.8（6.2），未接受过ERT的患者分别为-4.8（6.5）和-3.1（6.7）。在第104周时，两个治疗组的CK和Hex4水平均通过cipa+mig治疗得到改善。3例患者因输液相关反应停止了OLE研究。未发现新的安全信号。长达104周的cipa+mig治疗与从基线开始总体维持改善（6MWD、生物标志物）或稳定（FVC）以及持续的疗效相关，并且耐受性良好，支持LOPD患者的长期获益。试验注册号：NCT04138277；试验开始日期：2019年12月18日。
