Fabry disease is a rare X-linked lysosomal disease, in which mutations in the gene encoding α-galactosidase A result in progressive cellular accumulation of globotriaosylceramide (GL-3) in various organs including the skin, kidney, and heart, often leading to life-threatening conditions. Enzyme replacement therapy is currently the standard therapy for the disease, to which two α-galactosidase A formulations have been approved: agalsidase α (Replagal®, Shire) and agalsidase β (Fabrazyme®, Sanofi). We have recently developed a biosimilar of agalsidase β, JR-051, and investigated its pharmacokinetics and pharmacodynamics to assess its bioequivalence to agalsidase β. In a randomized phase I study, healthy adult male volunteers were treated with JR-051 or agalsidase β and the pharmacokinetics of the drugs were compared. The ratio of geometric means (90% confidence interval [CI]) of the AUC_0–24 and C_max for JR-051 over agalsidase β were 0.91 (0.8294, 1.0082) and 0.90 (0.7992, 1.0125), respectively. In a 52-week, single-arm, phase II/III study, patients with Fabry disease switched therapy from agalsidase β to JR-051 to evaluate its pharmacodynamics. The mean (95% CI) plasma GL-3 concentrations at weeks 26 and 52 relative to pre-JR-051 administration were 1.03 (0.91, 1.15) and 0.96 (0.86, 1.06), respectively, which were within the pre-determined bioequivalence acceptance range (0.70, 1.43). The mean (95% CI) plasma globotriaosylsphingosine (lyso-GL-3) concentrations at weeks 26 and 52 relative to pre-JR-051 administration were 1.07 (0.92, 1.23) and 1.13 (1.03, 1.22), respectively. Estimated glomerular filtration rate and left ventricular mass index, as renal and cardiac function indicators, showed no notable changes from baseline throughout the study period, and no new safety concerns were identified. In conclusion, these studies demonstrated bioequivalence of JR-051 to agalsidase β in terms of its pharmacokinetics and pharmacodynamics. JR-051 offers a potential new treatment option for patients with Fabry disease.

法布里病是一种罕见的X连锁溶酶体病，其中编码α-半乳糖苷酶A的基因中的突变会导致球果糖神经酰胺（GL-3）在包括皮肤，肾脏和心脏在内的各种器官中进行性细胞蓄积，这通常会导致生命威胁条件。酶替代疗法目前是该疾病的标准疗法，已经批准了两种α-半乳糖苷酶A制剂：阿糖苷酶α（夏尔）和阿糖苷酶β（赛诺菲）。我们最近开发了一种半乳糖苷酶β，JR-051的生物仿制药，并研究了其药代动力学和药效学，以评估其与半乳糖苷酶β的生物等效性。在一项随机I期研究中，健康的成年男性志愿者接受了JR-051或阿加糖酶β的治疗，并比较了药物的药代动力学。_{0 – 24}和_最大C与琼脂糖酶相比，JR-051的β分别为0.91（0.8294，1.0082）和0.90（0.7992，1.0125）。在一项为期52周的单臂II / III期研究中，患有法布里（Fabry）病的患者将治疗从阿加糖苷酶β转换为JR-051，以评估其药效学。相对于JR-051给药前，第26和52周的平均血浆GL-3浓度（95％CI）分别为1.03（0.91、1.15）和0.96（0.86、1.06），处于预定的生物等效性范围内接受范围（0.70，1.43）。相对于JR-051之前的给药，第26和52周时血浆中的球果糖神经鞘氨醇（lyso-GL-3）平均浓度（95％CI）分别为1.07（0.92，1.23）和1.13（1.03，1.22）。估计的肾小球滤过率和左心室质量指数，作为肾和心功能指标，在整个研究期间，与基线相比没有明显变化，也没有发现新的安全隐患。总之，这些研究证明了从药代动力学和药效学角度来看，JR-051与半乳糖苷酶β具有生物等效性。JR-051为法布里病患者提供了潜在的新治疗选择。