效率！FDA同时批准罗氏Pirfenidone和勃林格殷格翰的Nintedanib

效率！FDA同时批准罗氏Pirfenidone和勃林格殷格翰的Nintedanib

                               
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发布日期：2014-10-16  来源：reuters  

10月15日，FDA同时批准了罗氏的纤维化抑制剂Pirfenidone（商品名Esbriet）和勃林格殷格翰的多蛋白激酶抑制剂Nintedanib（商品名Ofev）用于治疗特发性肺纤维化，比预定的PDUFA日期提前很多（Esbriet的PDUFA为11月23日，Ofev的PDUFA为2015年1月2日），显示FDA对于重要药物的审批效率。特发性肺纤维化患者则有望结束无药可用的时代。

特发性肺纤维化的英文为Idiopathic Pulmonary Fibrosis， 简称IPF。Idiopathic为idiot（傻瓜）和pathology(病理)的复合词，意思是我们对于这个病的发病机理几乎不了解。但这个病的预后是很清楚的，死亡率比很多癌症还高，3年死亡率为50%。这个病相对罕见（谢天谢地！），美国现有13万病人，每年有数千新病例。在这两个药物批准之前，除了肺移植只有保守疗法，只能减少患者一些痛苦。Esbriet和Ofev在临床实验中都显示能减缓肺活量的下降速度，Esbriet还减慢6分钟行走测试的恶化速度，但两个药物都未能改善呼吸系统症状。

Esbriet原是Intermune所发明，今年8月被罗氏以83亿美元天价收购。Esbriet共做了四个临床实验，前三个疗效信号不明显，所以FDA没有批准，但分别在2008和2011年在日本和欧盟上市。今年的第四个临床实验结果说服FDA这个产品利大于弊，获得FDA的快速审批、优先审批、突破性药物、孤儿药四重地位，并在PDUFA前被批准上市，说明只要你的产品能解决目前的疑难杂症，即使效果还不尽人意，你也不用担心FDA的效率。反过来如果FDA成为你产品上市的障碍，你最好首先反思你那鸡肋药物是否值得浪费社会资源和对得起临床实验患者所冒的风险。

Ofev同样获得FDA的快速审批、优先审批、突破性药物、孤儿药四重地位，更比PDUFA提前两个半月批准上市（FDA这余地也留的大了点哈）。Ofev是多蛋白激酶抑制剂，至少抑制PDGF、FGF、VEGF受体。一个蛋白激酶抑制剂如果选择性这么差，很可能还抑制和上述每个受体同族的其它蛋白激酶。Ofev显然不是通过目前的一个靶点对应一个疾病的研发理念发现的。具体的发现过程我也没有仔细查，但可以肯定这是一个动物模型驱动的研发项目而机理本身起的作用非常有限。Esbriet也同样机理不清。对于IPF这样病理未知的复杂疾病绕过机理显然是个合理的策略。

当然这两个药物的疗效还相当轻微，并且不能用于重症病人。Esbriet不能用于肾功能障碍患者，Ofev不能用于肝功能障碍患者。但这毕竟是个突破性进展，而且由于两个药物机理不同可能以后可以联合使用。现在IPF的诊断也有进展，可望在发病前诊断，这样更早期用药可能效果更好。总之，今天IPF病人终于可以喘口气了(both literally and metaphorically)。

updat 2-FDA approves two treatments from Roche, Boehringer for fatal lung disorder

* First-ever U.S. approvals for idiopathic pulmonary fibrosis

* Roche's Esbriet to be priced at about $94,000 per year

* Esbriet expected to generate sales of about $1.04 billion in 2019 (Adds pricing details for Roche drug)

By Natalie Grover

Oct 15 (Reuters) - The U.S. health regulator approved two treatments for use in idiopathic pulmonary fibrosis (IPF), marking its first-ever approvals for the fatal lung disease that has no clear etiology and no cure.

The first, Esbriet, was developed by InterMune Inc, which Switzerland-based Roche Holding AG agreed to buy for $8.3 billion in August, banking largely on the treatment's potential.

Privately held German drugmaker Boehringer Ingelheim's rival drug nintedanib, which will be sold under the brand name Ofev, also won U.S. Food and Drug Administration approval on Wednesday. (1.usa.gov/1qwyxk5)

The agency's decision marks a crucial milestone in the management of the disease, which affects about 100,000 people in the United States.

IPF is characterized by scarring that thickens the lining of the lungs, causing an irreversible loss of the tissue's ability to transport oxygen.

Roche's drug, known generically as pirfenidone, is already sold in Europe and Canada to slow the progression of the often misdiagnosed, ultimately fatal disorder. (1.usa.gov/1qwx6Cj)

Esbriet, which joins Pulmozyme and Xolair in Roche's respiratory portfolio, is expected to launch within two weeks at an annual cost of about $94,000, Roche said.

Dr. Paul Noble, who says he was involved in the development of both drugs, believes that Roche's pirfenidone will be prescribed more frequently than Boehringer's nintedanib, at least until U.S. doctors become comfortable with the latter.

There is a lot more experience with pirfenidone as it has been studied for the better part of a decade, he said.

"The key differentiating factor of InterMune's drug seems to be in the reduction of all-cause mortality," Helvea analyst Odile Rundquist said.

The FDA rejected Esbriet in 2010, going against the recommendations of an independent review committee and asking for a fresh trial to prove the drug's effectiveness.

Data from this pivotal late-stage study showed that Esbriet was more effective than a placebo.

Esbriet, which rakes in sales of about $150 million a year in Canada and Europe, is expected to generate about $1.04 billion in 2019, according to Thomson Reuters Pharma.

Pirfenidone, like nintedanib, acts as "promiscuous inhibitor" of the action of multiple growth factors believed to be behind the scarring in IPF, said Noble, who is director of the Women's Guild Lung Institute at Cedars-Sinai.

Other drug developers, including Gilead Sciences Inc , Bristol-Myers Squibb and Biogen Idec, also have IPF drugs in mid-stage development.

The future lies in a combination treatment that can actually reduce scar tissue, Noble said.

Roche shares closed down about 2 percent at 258.90 Swiss francs ($275.27) on the SIX Swiss Exchange.

($1 = 0.9405 Swiss francs) (Editing by Simon Jennings)

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