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利用针对被忽视热带病的药物创制战略伙伴关系开发 E1224。

Development of E1224 by leveraging a strategic partnership for the medicines creation against neglected tropical diseases.

机构信息

Global Health Research Section, hhc Data Creation Center, Eisai Co., Ltd., 1-3, Tokodai 5-chome, Tsukuba-shi, Ibaraki 300-2635, Japan.

出版信息

Parasitol Int. 2021 Apr;81:102278. doi: 10.1016/j.parint.2020.102278. Epub 2020 Dec 25.

DOI:10.1016/j.parint.2020.102278
PMID:33370607
Abstract

Neglected tropical diseases (NTDs) are communicable diseases that are uncommon in developed countries but epidemic in developing countries in tropical and subtropical regions of the world. One of the important contributions expected of pharmaceutical companies is the development and provision of drugs effective against NTDs. Eisai's efforts toward improving global health have resulted in a rich portfolio of assets addressing six infectious diseases: malaria, tuberculosis, Chagas disease, lymphatic filariasis, leishmaniasis, and mycetoma. As the most advanced project, Eisai has developed E1224 (fosravuconazole l-lysine ethanolate), which is available in both intravenous and oral formulations, and provides ravuconazole, an active form of fosravuconazole, with a long plasma half-life. The first clinical trials of E1224, for Chagas disease, have already been completed, led by the Drugs for Neglected Diseases initiative (DNDi). As a result, parasite clearance was observed with E1224 during the treatment phase, but parasite regrowth was observed after the end of drug administration, suggesting that the mechanism of action of E1224 on Trypanosoma cruzi is static rather than parasiticidal. On the other hand, a clinical trial for eumycetoma in collaboration with DNDi is ongoing supported by the Global Health Innovative Technology Fund, and is examining the efficacy of weekly treatment with E1224 versus the current standard of care, daily treatment with itraconazole. In this manner, Eisai will continue its drug-discovery research projects in collaboration with various PDPs and academia supported by funding agencies.

摘要

被忽视的热带病(NTDs)是在发达国家不常见但在世界热带和亚热带地区发展中国家流行的传染病。制药公司的一项重要贡献预计是开发和提供针对 NTDs 的药物。卫材公司为改善全球健康所做的努力产生了丰富的资产组合,涵盖了六种传染病:疟疾、结核病、恰加斯病、淋巴丝虫病、利什曼病和真菌病。作为最先进的项目,卫材公司开发了 E1224(伏立康唑赖氨酸乙酯),它有静脉内和口服两种制剂,提供了福沙伏康唑的活性形式,具有较长的血浆半衰期。由被忽视疾病药物研发倡议(DNDi)牵头,E1224 治疗恰加斯病的首次临床试验已经完成。结果,在治疗阶段观察到 E1224 可清除寄生虫,但在药物治疗结束后观察到寄生虫再生,这表明 E1224 对克氏锥虫的作用机制是静态的,而不是杀寄生虫的。另一方面,在全球健康创新技术基金的支持下,卫材公司与 DNDi 合作开展了一项针对真菌病的临床试验,正在研究每周用 E1224 治疗与目前的标准治疗(每天用伊曲康唑治疗)的疗效。通过这种方式,卫材公司将继续与各种 PDP 和资助机构支持的学术界合作开展药物发现研究项目。

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