Enzyme replacement therapy in Japanese Fabry disease patients: The results of a phase 2 bridging study
Enzyme replacement therapy in Japanese Fabry disease patients: The results of a phase 2 bridging study
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DOI：
10.1007/s10545-005-0575-y
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发表时间：
2005-08-01
影响因子：
4.2
通讯作者：
Saito, H
中科院分区：
文献类型：
--
作者：
Eto, Y;Ohashi, T;Saito, H
法布里病（α -半乳糖苷酶A缺乏症）是一种x连锁的遗传性疾病，导致溶酶体中globotriaosylceramide （GL-3）的病理性积累，特别是在肾脏、心脏和大脑的血管内皮中。我们报告了一项开放标签ii期研究的结果，该研究旨在评估种族差异是否会影响日本人群中Fabry患者的agalsidase β (Fabrazyme)治疗的安全性和有效性。该研究设计反映了已完成的3期临床试验的设计，该试验导致了产品agalsidase β的批准。13名日本男性法布里患者参加了这项研究，在20周的时间里，每两周注射一次酶替代疗法。所有选定的疗效终点均显示与3期研究结果相当的改善。这些改善包括肾脏和皮肤毛细血管内皮细胞中GL-3积聚减少到（接近）正常水平（92%的患者）。经ELISA检测，肾脏和血浆GL-3水平分别下降51.9%和100%。肾功能保持正常。法布里相关疼痛和生活质量在多个类别中都比基线有所改善。相关不良事件的强度为轻度或中度，主要与输液相关（发烧和僵直）。正如预期的那样，在85%的患者中观察到IgG抗体的形成，但对治疗反应没有影响。这些结果表明，在日本法布里病患者中，琼脂苷酶治疗是安全有效的。在安全性和有效性方面，与高加索人群相比没有观察到差异。
Fabry Disease (alpha-galactosidase A deficiency) is an X-linked hereditary disorder leading to the pathological accumulation of globotriaosylceramide (GL-3) in lysosomes, particularly in the vascular endothelium of the kidney, heart and brain. We report the results of an open-label phase 2 study that was undertaken to evaluate whether ethnic differences exist that would affect agalsidase beta (Fabrazyme) treatment of Fabry patients in the Japanese population, relative to safety and efficacy. The study design mirrored the design of the completed phase 3 clinical trial that led to approval of the product agalsidase beta. The 13 Japanese, male Fabry patients enrolled in the study received the enzyme replacement therapy over a period of 20 weeks as biweekly infusions. All selected efficacy end points showed improvements that were comparable with findings from the phase 3 study. These improvements included reductions of GL-3 accumulation in both kidney and skin capillary endothelial cells to (near) normal levels (92% of patients). Kidney and plasma GL-3 levels decreased by 51.9% and 100%, respectively, by ELISA. Renal function remained normal. Fabry-associated pain, and quality of life, showed improvement over baseline in multiple categories. Related adverse events were mild or moderate in intensity and mostly infusion-associated (fever and rigors). As expected, IgG antibody formation was observed in 85% of the patients, but had no effect on treatment response. These results suggest that treatment with agalsidase beta is safe and effective in Japanese patients with Fabry disease. With regard to safety and efficacy, no differences were observed as compared to the caucasian population.