Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months.
Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months.
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DOI：
10.1007/s10545-017-0123-6
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发表时间：
2018-09
影响因子：
4.2
通讯作者：
Puga AC
中科院分区：
文献类型：
--
作者：
Wasserstein MP;Diaz GA;Lachmann RH;Jouvin MH;Nandy I;Ji AJ;Puga AC
Olipudase alfa是一种重组人酸性鞘磷脂酶（ASM），是一种酶替代疗法，用于治疗酸性鞘磷脂酶缺乏症（ASMD）的非神经系统表现。这项正在进行的、开放标签、长期研究（NCT 02004704）在5例成人ASMD患者中评估了30个月治疗后的lipudase alfa的安全性和疗效。30个月治疗期间未发生死亡、严重或重度事件或停药。大多数不良事件为轻度，包括头痛、恶心和腹痛。无患者产生抗药抗体，生命体征、血液学或心脏安全性参数无临床显著不良变化。在30个月的治疗期间，肝脏（31%）和脾脏（39%）体积保持统计学显著性降低。肺弥散量平均增加35%，浸润性肺病参数有临床相关改善。所有患者的血脂水平均有所改善。在一些患者中观察到脊柱骨密度的改善。血清中的壳三糖苷酶和干血斑中的溶血鞘磷脂随着脂质体酶α治疗而降低，表明可用作监测治疗疗效的生物标志物。Olipudase alfa是第一个针对ASMD开发的病因特异性治疗药物。这项研究表明，用脂肪酶α治疗30个月耐受性良好，并与相关疾病临床指标的持续改善有关。本文的在线版本（10.1007/s10545-017-0123-6）包含补充材料，可供授权用户使用。
Olipudase alfa, a recombinant human acid sphingomyelinase (ASM), is an enzyme replacement therapy for the treatment of nonneurologic manifestations of acid sphingomyelinase deficiency (ASMD). This ongoing, open-label, long-term study (NCT02004704) assessed safety and efficacy of olipudase alfa following 30 months of treatment in five adult patients with ASMD. There were no deaths, serious or severe events, or discontinuations during 30 months of treatment. The majority of adverse events were mild and included headache, nausea, and abdominal pain. No patient developed anti-drug antibodies and there were no clinically significant adverse changes in vital signs, hematology, or cardiac safety parameters. Statistically significant reductions in liver (31%) and spleen (39%) volumes were maintained through 30 months of treatment. There was a mean increase in lung diffusing capacity of 35%, and clinically relevant improvements in infiltrative lung disease parameters. Lipid profiles improved in all patients. Improvements in bone mineral density of the spine were observed in some patients. Chitotriosidase in serum and lyso-sphingomyelin in dried blood spots decreased with olipudase alfa treatment, suggesting utility as biomarkers for monitoring treatment efficacy. Olipudase alfa is the first etiology-specific treatment in development for ASMD. This study demonstrates that treatment with olipudase alfa for 30 months is well-tolerated and associated with life-transforming sustained improvements in relevant disease clinical measures. The online version of this article (10.1007/s10545-017-0123-6) contains supplementary material, which is available to authorized users.
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