[转载]InterMune治疗IPF药物prifenidone获得FDA突破性药物认证

   日期:2019-09-21     来源:科学网    作者:秦天明    浏览:5070    评论:0    
核心提示:InterMune ($ITMN) secured the FDA's breakthrough therapy designation for its in-development treatment of a rare lung

InterMune ($ITMN) secured the FDAs breakthrough therapy designation for its in-development treatment of a rare lung disease, evening the regulatory score with rival Boehringer Ingelheim as the two angle for position on the U.S. market.

The biotechs drug, pirfenidone, treats the often-fatal idiopathic pulmonary fibrosis (IPF), a lung-scarring disease that inhibits oxygen absorption, leading to shortness of breath and poor pulmonary function. The FDAs breakthrough tag guarantees an expedited review and access to the agencys senior staff, but InterMune isnt expecting the nod to change the drugs timeline for approval.

Pirfenidone already picked up the FDAs promise of a priority review, and the addition of a breakthrough designation doesnt dial up the agencys speed, InterMune said in an email. That said, the FDAs promise to "involve senior FDA managers and provide additional resources to coordinate cross-disciplinary review" could make a difference in time, but thats entirely at the agencys discretion, InterMune said.

As it stands, InterMune expects to win approval for pirfenidone by November, launching the drug in the first quarter of 2015 if all goes according to plan.

The breakthrough designation comes just one day after Boehringer Ingelheim, maker of a rival IPF treatment, received the same honor. Like its competitor, Boehringers nintedanib had already won a priority review designation, and the German drugmaker hasnt disclosed its expected timeline for approval.

InterMunes drug endured an FDA rejection back in 2010, but, after heading back to the clinic and returning with some stellar new Phase III data, the biotech worked its way back into the agencys good graces, resubmitting the drug in May.

There are no FDA-approved treatments for IPF, which kills about 40,000 people a year, according to the Coalition for Pulmonary Fibrosis. Pirfenidone has been on the market overseas for a few years but has yet to generate any notable sales momentum, bringing in just $70.2 million last year.

Analysts figure the U.S. market for IPF drugs could top out at above $2 billion, but whether InterMune or Boehringer claims the lions share remains the subject of debate. Both drugs have charted impressive results in Phase III, but each has missed out on at least one secondary endpoint in its late-stage program.

Pirfenidone works by inhibiting two cytokines: TGF-beta, which controls a slew of cell functions and plays a part in fibrosis; and TNF-alpha, which has an active role in inflammation. In pivotal studies, the drug significantly reduced patients decline in lung function compared to placebo, also meeting a secondary endpoint of performance on a 6-minute walking test.

 

InterMune公司最近透露FDA已经确认授予其开发的治疗原发性肺纤维化(IPF)药物prifenidone突破性药物疗法,但并不会加快FDA对该药物的上市审核进程。原发性肺纤维化会导致肺部结构损伤,从而抑制肺部吸入氧气致使患者呼气困难,甚至会导致死亡。在FDA的先期审查中,pirfenidone已经获得了相关专家的高度认可,因而此次获得突破性药物认证可能并不会加速这一药物的审核。按照原计划,InterMune公司希望今年11pirfenidone能够获得FDA审核,并于2015年上市。prifenidone的这一认证也仅比竞争对手Boehringer Ingelheim公司的IPF药物nintedanib晚一天。不过后者并未透露nintedanib上市审批的具体计划。

吡非尼酮(Pirfenidone, Pirespa, EsbrietEtuary)是由美国Marnac公司开发的具有抗纤维化作用的化合物,19974月,日本盐野义(Shionogi)制药获得日本、韩国和台湾的开发权。除了这三个市场外,20024月,InterMune公司获得了Marnac公司将该化合物除以上三个市场外的全球开发权许可给位于美国加州的InterMune公司。

200810月,吡非尼酮由盐野义制药申请最先在日本获批上市,商品名Pirespa,成为第一个在全球获得批准用于治疗特发性肺纤维化(IPF)的药物。20109月仿造药公司Cipla已在印度推出吡非尼酮,商品名为Pirfenex2011年,吡非尼酮(pirfenidone)获欧盟和加拿大批准,商品名为Esbriet

200412月吡非尼酮(F647,Pirfenidone)最先由上海睿星基因技术有限公司(Shanghai Genomics)向国家食品药品监督管理局(SFDA)申请注册,由于当时该品并没有在国外上市,因此按化学药1:1类新药(Category 1.1 Novel Chemical Compound Drug)进行申报,2005511日获得临床批件。

上海睿星基因技术有限公司成立于20018月,由留美博士罗楹(Ying Luo)、吴骏(Jun Wu)等多名归国留学人员创办,由上海创业投资有限公司和上海张江高科技园区开发股份有限公司共同出资,后由GNI株式会社投资,注册资金人民币7650万元。

GNI集团(GNI Group)是一家在日本东京证券市场上市的国际性的新药研发企业,2001年由具有美日双重国籍的Christopher Savoie等人在美国加州创办,总部设在东京,2007年在日本东京证券上市(代码:2160),其主要投资的研发、生产和销售均在中国上海和北京等地。20056GNI集团与上海睿星基因技术有限公司合并,上海睿星基因技术有限公司成为GNI集团子公司。

20056月吡非尼酮临床I期研究在武汉协和医院正式开始。

2006年,由协和医院牵头组织中国医大一附院、北京朝阳医院、上海肺科医院、河南省人民医院、沈阳军区总医院进开展吡非尼酮临床研究。

20081017日日本盐野义(Shionogi)公司率先在日本上市。此后,国内多家企业又陆续按3.1类新药申报该药。

2009年上海睿星基因技术有限公司完成临床试验,申报新药证书。

2010年,吡非尼酮通过新药审评。

20119月,上海睿星基因技术有限公司获得国家食品药品监督管理局颁发的1.1类新药证书

2011年,日本GNI集团和上海睿星基因技术有限公司先后入资北京康蒂尼药业有限公司,GNI集团拥有北京康蒂尼药业51%的股份。北京康蒂尼药业有限公司引入国家1.1类肺纤维化特效新药吡非尼酮并开始生产。北京康蒂尼药业有限公司始建于2002年,位于北京市顺义区林河工业开发区.

2012年,治疗肺纤维化1.1类新药吡非尼酮工艺升级和生产线建设项目纳入国家政府股权投资重大项目,北京市科委股权融资1000万元,由中关村发展集团代持。

20131225日获得国家食品药品监督管理局颁发的吡非尼酮生产批件,吡非尼酮(国药准字H20133375),吡非尼酮胶囊(国药准字H20133376),生产单位(北京康蒂尼药业有限公司),商品名:艾思瑞,英文商品名:Etuary,日文商品名:アイスーリュイ

20141月艾思瑞(吡非尼酮胶囊,Etuary, Pirfenidone,アイスーリュイ)正式在中国上市销售,是我国第一个治疗肺纤维化的药物。

吡非尼酮合成路线如下:

5-甲基-2-氨基吡啶经过重氮化反应,制备相应的重氮盐,经过亲核芳香取代反应,引入羟基,异构化为吡啶酮化合物,在Cu的作用下经过Ullmann型偶联(Goldberg reaction)即制备出Pirfenidone



 
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