Safety, Efficacy, and Pharmacokinetics of Agalsidase Alfa in Treatment-Naive Chinese Patients with Fabry Disease: 52-Week Phase 3, Open-Label, Single-Arm Study

Clinical data on the efficacy, tolerability, and pharmacokinetics of agalsidase alfa in Chinese patients with Fabry disease are limited. We evaluated the safety, efficacy, and pharmacokinetics of agalsidase alfa in Chinese patients who are treatment-naive over 52 weeks. This was an open-label, non-randomized, single-arm, multicenter (six centers in China) phase 3 study. Patients with Fabry disease (aged 7–65 years; either sex) received agalsidase alfa 0.2 mg/kg intravenously (every other week for up to 52 weeks). The primary endpoint was the incidence of serious treatment-emergent adverse events (TEAEs). Secondary endpoints included the incidence of TEAEs, changes from baseline in estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF), and agalsidase alfa pharmacokinetics. Overall, 20 patients were enrolled (May 2022 to January 2024) and received ≥ 1 dose of agalsidase alfa. The median number of infusions was 27; median exposure duration was 12.0 months. Agalsidase alfa was generally well tolerated. Two patients (10.0%) reported one serious TEAE each (sepsis, ectopic pregnancy). All patients reported ≥ 1 TEAE, most of which were mild or moderate (98.2%); nine patients (45.0%) had ≥ 1 TEAE assessed as related to treatment. Baseline eGFR, LVMI, and LVEF were 118.8 (21.4) mL/min/1.73 m 2 , 38.0 (11.2) g/m 2.7 , and 66.8% (4.9), respectively. Renal function and cardiac structure and function remained relatively stable over 52 weeks; mean (SD) changes in eGFR, LVMI, and LVEF from baseline were 4.1 (12.5) mL/min/1.73 m 2 , 0.56 (8.71) g/m 2.7 , and 0.8% (3.3%), respectively. Agalsidase alfa exposure (area under the concentration–time curve and maximum serum concentration) was generally similar at week 0 and at week 28. Data from this 52-week study support the use of agalsidase alfa as a long-term treatment option for Chinese patients with Fabry disease. Safety, efficacy, and pharmacokinetic profiles were consistent with studies in other populations. Graphical Abstract available for this article. NCT04974749