东京——经过约15年的研发，日本武田制药已全面推出Orzeyful，这是一种针对病因而非仅缓解症状的发作性睡病治疗药物。
TOKYO -- After roughly 15 years of development, Japan's Takeda Pharmaceutical has fully launched Orzeyful, a narcolepsy treatment that targets the root cause rather than addressing only the symptoms.
武田于2011年前后启动了这个最终催生Orzeyful的项目。该药物于10月15日在日本市场上市。
Takeda started the project that gave rise to Orzeyful around 2011. The drug was released in the Japanese market on Oct. 15.
发作性睡病的典型表现是白天极度困倦和突然打瞌睡，其病因可能是大脑中一种名为食欲素的蛋白质缺乏。Orzeyful通过与食欲素受体结合，起到替代食欲素的作用。
Narcolepsy, exemplified by intense daytime sleepiness and sudden bouts of dozing off, can be caused by a deficiency of a brain protein called orexin. Orzeyful acts as a substitute for orexin by binding to the protein's receptors.
Orzeyful是首个具有这一功能的发作性睡病药物。武田的一位代表表示，该药“有潜力针对疾病的根本病因，一次性治疗多种症状”。
Orzeyful is the first drug for narcolepsy with this function. The medicine "has the potential to address the root cause of the disease and treat various symptoms all at once," a Takeda representative said.
食欲素是一种大分子，直接给患者用药时难以进入大脑内部。Orzeyful化合物需要被制成食欲素大小的五分之一到六分之一，才能被递送到大脑中正确的受体。
As a large molecule, it is difficult for orexin to reach the inside of the brain when administered externally into a patient. The Orzeyful compound needed to be made one-fifth to one-sixth the size of orexin so that it could be delivered to the correct brain receptors.
“当时有人怀疑，如此小的分子能否像食欲素一样激活受体，”领导Orzeyful研发项目的武田执行董事木村治秀说。“人们认为，开发带有这类限制条件的药物是不可能的。”武田从公司200万种化合物的库中筛选候选分子，只找到一个有希望的先导化合物，后者推动了Orzeyful的后续开发。
"At the time, there were doubts about whether such a small molecule could activate receptors in the same way as orexin," said Haruhide Kimura, executive director at Takeda who led Orzeyful's development project. "It was thought that a drug with those kinds of stipulations would be impossible to develop." Takeda sifted the company's library of 2 million compounds for candidates. The company found only one promising lead, which later spurred the development of Orzeyful.
“在过去的研发项目中，我们每当发现有趣的化合物，就会不断将其加入化合物集合，”木村说。“长期研究的积累把我们带到了今天。”武田制药于10月15日在日本市场推出Orzeyful。（武田制药）2021年，发作性睡病的有希望候选药物TAK-994因肝毒性高而暂停临床试验。2023年，该药物的开发被终止。
"In past research projects, we repeatedly added interesting compounds to the set whenever we found them," Kimura said. "The accumulation of research over the long term has led us to where we are today." Takeda Pharmaceutical released Orzeyful in the Japanese market on Oct. 15. (Takeda Pharmaceutical) In 2021, clinical trials for TAK-994, a promising candidate for narcolepsy, were suspended due to high liver toxicity. In 2023, development was discontinued.
尽管TAK-994的结果让项目团队陷入动荡，Orzeyful在开发过程中取得了良好结果。
Though TAK-994's outcome roiled the project team, Orzeyful achieved favorable results during development.
近年来，武田药品专注于销售其他公司开发的产品或收购开发权。Orzeyful是武田药品多年来首个自主研发的产品。
In recent years, Takeda has focused on selling products developed by other companies or acquiring development rights. Orzeyful is the first product in years that Takeda has developed in-house.
武田药品预计Orzeyful将实现20亿至30亿美元的全球销售额，这将使该药物稳居大热门药物行列。
Takeda anticipates Orzeyful attaining $2 billion to $3 billion in global sales, which would put the drug firmly in the blockbuster category.
1998年，日本筑波大学教授柳泽正史发现了食欲素。今年9月，柳泽正史与斯坦福大学教授Emmanuel Mignot共同获得了享有盛誉的拉斯克基础医学研究奖。
Orexin was discovered in 1998 by Masashi Yanagisawa, a professor at Japan's University of Tsukuba. Yanagisawa was awarded the prestigious Albert Lasker Basic Medical Research Award in September together with Emmanuel Mignot, a professor at Stanford University.
木村表示：“多亏了柳泽先生和斯坦福大学的Emmanuel Mignot教授，我们才能研制出这种药物。”
"We were able to create this drug thanks to Mr. Yanagisawa and professor Emmanuel Mignot of Stanford University," Kimura said.