A phase 4, open-label, multicenter study of the safety and efficacy of agalsidase beta in Chinese patients with Fabry disease

TL;DR

This study shows agalsidase beta is safe and effective for Chinese Fabry disease patients, with potential impacts from COVID-19 on kidney outcomes.

Contribution

The first phase 4 study of agalsidase beta in Chinese Fabry disease patients, including analysis of COVID-19's impact on prognosis.

Findings

Agalsidase beta reduced plasma GL-3 and Lyso-GL-3 levels significantly over 48 weeks.

Younger patients (<30 years) showed greater symptom improvement and better renal outcomes than older patients.

Patients infected with COVID-19 had less pronounced treatment benefits compared to uninfected patients.

Abstract

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 m2/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.

Trial registration: ClinicalTrials.gov, NCT05054387. Registered 09 September 2021, https://clinicaltrials.gov/study/NCT05054387

The online version contains supplementary material available at 10.1186/s13023-025-03950-7.

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