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奥扎莫德治疗复发缓解型多发性硬化。

Ozanimod for the treatment of relapsing remitting multiple sclerosis.

机构信息

a NeuroCure Clinical Research Center , Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health , Berlin , Germany.

b Experimental and Clinical Research Center , Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität, and Berlin Institute of Health , Berlin , Germany.

出版信息

Expert Opin Pharmacother. 2018 Dec;19(18):2073-2086. doi: 10.1080/14656566.2018.1540592. Epub 2018 Nov 8.

Abstract

Ozanimod is a selective sphingosine 1-phosphate receptor 1 and 5 modulator under development by Celgene, for the treatment of relapsing remitting multiple sclerosis. Extensive clinical experience has become available for the related compound fingolimod, favoring the sphingosine 1-phosphate therapeutic concept. Off-target effects have been attributed to its low receptor specificity and have prompted the development of next generation sphingosine 1-phosphate receptor modulators. Areas covered: The authors evaluate the literature of ozanimod, using the PubMed database as well as repositories of the European Committee for Treatment and Research in Multiple Sclerosis and the American and European Academy of Neurology. Specifically, the authors cover and discuss the preclinical data on ozanimod, pharmacokinetics and dynamics, and data on efficacy and safety from the pivotal trials. Expert opinion: Superiority of ozanimod over intramuscular interferon β-1a with regard to reduction in annualized relapse rate and magnetic resonance imaging outcomes has been shown in two phase III trials. The beneficial effect on brain volume and gray matter loss are encouraging and in line with data on other newer immunomodulators. Ozanimod is a valuable contribution to the therapeutic armamentarium in MS, although the effect on disability progression is unclear and requires further investigations.

摘要

奥扎莫德是一种由 Celgene 开发的鞘氨醇 1-磷酸受体 1 和 5 调节剂,用于治疗复发缓解型多发性硬化症。相关化合物芬戈莫德已有广泛的临床经验,支持鞘氨醇 1-磷酸治疗概念。非靶点效应归因于其低受体特异性,并促使开发下一代鞘氨醇 1-磷酸受体调节剂。

涵盖领域

作者使用 PubMed 数据库以及欧洲多发性硬化症治疗和研究委员会、美国和欧洲神经病学学会的存储库,评估了奥扎莫德的文献。具体来说,作者涵盖并讨论了奥扎莫德的临床前数据、药代动力学和药效学,以及来自关键试验的疗效和安全性数据。

专家意见

两项 III 期试验表明,奥扎莫德在降低年复发率和磁共振成像结果方面优于肌肉内干扰素β-1a。对脑容量和灰质损失的有益影响令人鼓舞,与其他新型免疫调节剂的数据一致。奥扎莫德是多发性硬化症治疗武器库的有价值贡献,尽管其对残疾进展的影响尚不清楚,需要进一步研究。

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