Ren Hong, Zhang Wei, Ouyang Yan, Guo Junhong, Xu Hong, Ma Jie, Luo Xiaoping, Pan Xiaoxia, Yuan Yun, Zhang Wei, Shen Qian, Li Bin, Feng Qiqi, Liu Shi, Chen Nan
Department of Nephrology, Institute of Nephrology, Ruijin Hospital, The Medical School of Shanghai Jiao Tong University, No. 197 Ruijin Er Road, Shanghai, China.
Department of Neurology, Peking University First Hospital, No. 8 Xishiku Street, Beijing, China.
Orphanet J Rare Dis. 2025 Aug 4;20(1):401. doi: 10.1186/s13023-025-03950-7.
This is the first phase 4 study evaluating safety and efficacy of enzyme replacement therapy (ERT) in Chinese patients with Fabry disease, and exploring the impact of COVID-19 infection on the prognosis of Fabry disease under ERT.
Eligible patients received an infusion of agalsidase beta (1.0 mg/kg/2w) for up to 48 weeks. The primary endpoint was the safety of agalsidase beta. The endpoints of efficacy included changes in plasma globotriaosylceramide (GL-3), globotriaosylsphingosine (Lyso-GL-3), symptoms and estimated glomerular filtration rate (eGFR) from baseline to week 48. A post-hoc subgroup analysis was conducted by age group (< 30 years and ≥ 30 years) and in patients with or without COVID-19 infection. All 22 patients completed the study and 14 of them were infected by COVID-19. Treatment-related adverse events (AEs) and infusion-associated reactions (IARs) were reported in 8 participants (36.4%). Mean plasma GL-3 (-34.6%) and Lyso-GL-3 (-60.3%) levels decreased from baseline to week 48. Thirteen participants (59.1%) experienced improved specific symptoms at week 48. There were no meaningful changes in eGFR during the study, and the overall population showed an annual eGFR slope of 0.43 mL/min/1.73 m/year (95% CI: -5.95 to 6.82). In the subgroup analysis, the reductions in plasma GL-3 and Lyso-GL-3 levels, improvement in symptoms, and attenuation of eGFR decline after 48 weeks of treatment were generally greater in patients aged < 30 years (n = 11) than in patients aged ≥ 30 years (n = 11), and less pronounced in the COVID-19 infected group (n = 14) than in the uninfected group (n = 8).
This study demonstrates that agalsidase beta is safe and effective in Chinese patients with Fabry disease, and suggestes that COVID-19 infection may potentially impact the renal prognosis for Fabry disease.
ClinicalTrials.gov, NCT05054387. Registered 09 September 2021, https://clinicaltrials.gov/study/NCT05054387.
这是第一项评估酶替代疗法（ERT）在中国法布里病患者中的安全性和有效性，并探索新型冠状病毒肺炎（COVID-19）感染对ERT治疗下法布里病预后影响的4期研究。
符合条件的患者接受阿加糖酶β（1.0mg/kg/2周）输注，最长48周。主要终点是阿加糖酶β的安全性。疗效终点包括从基线到第48周血浆球三糖基神经酰胺（GL-3）、球三糖基鞘氨醇（Lyso-GL-3）、症状和估计肾小球滤过率（eGFR）的变化。按年龄组（<30岁和≥30岁）以及有无COVID-19感染进行事后亚组分析。所有22例患者完成了研究，其中14例感染了COVID-19。8名参与者（36.4%）报告了与治疗相关的不良事件（AE）和输注相关反应（IAR）。从基线到第48周，血浆GL-3（-34.6%）和Lyso-GL-3（-60.3%）平均水平下降。13名参与者（59.1%）在第48周时特定症状有所改善。研究期间eGFR无显著变化，总体人群的年eGFR斜率为0.43mL/min/1.73m²/年（95%CI：-5.95至6.82）。在亚组分析中，年龄<30岁（n=11）的患者在治疗48周后血浆GL-3和Lyso-GL-3水平的降低、症状的改善以及eGFR下降的减轻通常比年龄≥30岁（n=11）的患者更明显，且在COVID-19感染组（n=14）中比未感染组（n=8）更不显著。
本研究表明阿加糖酶β在中国法布里病患者中安全有效，并提示COVID-19感染可能会影响法布里病的肾脏预后。
ClinicalTrials.gov，NCT05054387。2021年9月9日注册，https://clinicaltrials.gov/study/NCT05054387 。
