Background and Objective

Fabry disease, an X-linked lysosomal storage disorder characterized by absent or reduced alpha-galactosidase activity, is a lifelong disease that impairs patients’ quality of life. Patients with Fabry disease have a considerably shortened lifespan, with mortality being mainly due to renal failure, cardiovascular disease, or cerebrovascular disease. Enzyme replacement therapy with agalsidase alfa has been shown to attenuate the renal, cardiovascular, and neuropathic disease progression associated with Fabry disease. The objective of this study was to investigate the safety of a new animal component-free version of agalsidase alfa.

Methods

A phase III/IV, open-label, single-arm, multicenter safety study was conducted in Canadian patients with Fabry disease between August 2011 and September 2017 as a regulatory requirement to assess the safety of agalsidase alfa produced using an animal component-free bioreactor process. Eligible patients had a documented diagnosis of Fabry disease and satisfied current Canadian guidelines for receiving enzyme replacement therapy for Fabry disease. Following treatment with animal component-free bioreactor-processed agalsidase alfa, treatment-emergent adverse events were monitored, and post hoc analyses of infusion-related reactions by antidrug antibody and neutralizing antibody statuses were conducted. The data were analyzed using descriptive statistics.

Results

A total of 167 patients (mean [standard deviation] age, 48.9 [14.8] years), including six pediatric patients (< 18 years of age), received at least one full or partial infusion of agalsidase alfa animal component-free. Fewer than 5% of treatment-emergent adverse events (212/4446) observed in 40 patients were reported as infusion-related reactions. Antidrug antibody and neutralizing antibody status did not affect the proportion of patients with infusion-related reactions. No clinically significant changes in vital signs were observed in patients over the course of the study.

Conclusions

Long-term treatment with bioreactor-produced agalsidase alfa animal component-free did not reveal new safety signals in this population of Canadian patients with Fabry disease. The treatment-emergent adverse event profile was consistent with the clinical manifestations of the disease and the known safety profile of roller bottle-produced agalsidase alfa.

Clinical Trial Registration

ClinicalTrials.gov identifier NCT01298141.

中文翻译：

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实施生物反应器过程后，阿加糖酶阿尔法酶替代疗法在加拿大法布里病患者中的安全性

背景与目的

法布里病是一种 X 连锁溶酶体贮积症，其特征是 α-半乳糖苷酶活性缺失或降低，是一种损害患者生活质量的终生疾病。法布里病患者的寿命显着缩短，死亡率主要是由于肾功能衰竭、心血管疾病或脑血管疾病。阿加糖酶 α 的酶替代疗法已被证明可以减轻与法布里病相关的肾脏、心血管和神经疾病的进展。本研究的目的是调查一种新的无动物成分版本的阿加糖酶 alfa 的安全性。

方法

作为监管要求，在 2011 年 8 月至 2017 年 9 月期间在加拿大法布里病患者中进行了一项 III/IV 期、开放标签、单臂、多中心安全性研究，以评估使用无动物成分的生物反应器生产的阿加糖酶 α 的安全性过程。符合条件的患者有法布里病的书面诊断，并满足加拿大目前接受法布里病酶替代疗法的指南。在用无动物成分的生物反应器处理的阿加糖酶 α 治疗后，监测治疗中出现的不良事件，并通过抗药抗体和中和抗体状态对输液相关反应进行事后分析。使用描述性统计分析数据。

结果

总共 167 名患者（平均 [标准差] 年龄，48.9 [14.8] 岁），包括 6 名儿科患者（<18 岁），接受了至少一次完全或部分无动物成分的阿加糖酶 α 输注。在 40 名患者中观察到的治疗出现的不良事件 (212/4446) 中不到 5% 被报告为输液相关反应。抗药抗体和中和抗体状态不影响输液相关反应患者的比例。在研究过程中，没有观察到患者生命体征的临床显着变化。

结论

在加拿大法布里病患者群体中，使用生物反应器生产的不含动物成分的阿加糖酶 alfa 进行长期治疗并没有显示出新的安全信号。治疗中出现的不良事件特征与疾病的临床表现和滚瓶生产的阿加糖酶 α 的已知安全性特征一致。

临床试验注册

ClinicalTrials.gov 标识符 NCT01298141。