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                您當前位置:網站首頁 >> 醫藥新聞 >> 新藥上市 >> 2014年10月FDA批準上市新藥nintedanib(寧特達尼)
               
               
              2014年10月FDA批準上市新藥nintedanib(寧特達尼)
              2014-11-24 09:56:30 來源:有機化學網 瀏覽:4950

              2014年10月15日,FDA同時批準了羅氏的纖維化抑制劑Pirfenidone(商品名Esbriet)和BI的多蛋白激酶抑制劑Nintedanib(商品名Ofev)用于治療特發性肺纖維化,比預定的PDUFA日期提前很多(Esbriet的PDUFA為11月23日,Ofev的PDUFA為2015年1月2日),顯示FDA對于重要藥物的審批效率。特發性肺纖維化患者則有望結束無藥可用的時代。

              特發性肺纖維化的英文為Idiopathic Pulmonary Fibrosis, 簡稱IPF。Idiopathic為idiot(傻瓜)和pathology(病理)的復合詞,意思是我們對于這個病的發病機理幾乎不了解。但這個病的預后是很清楚的,死亡率比很多癌癥還高,3年死亡率為50%。這個病相對罕見(謝天謝地!),美國現有13萬病人,每年有數千新病例。在這兩個藥物批準之前,除了肺移植只有保守療法,只能減少患者一些痛苦。Esbriet和Ofev在臨床實驗中都顯示能減緩肺活量的下降速度,Esbriet還減慢6分鐘行走測試的惡化速度,但兩個藥物都未能改善呼吸系統癥狀。

              Esbriet原是Intermune所發明,今年8月被羅氏以83億美元天價收購。Esbriet共做了四個臨床實驗,前三個療效信號不明顯,所以FDA沒有批準,但分別在2008和2011年在日本和歐盟上市。今年的第四個臨床實驗結果說服FDA這個產品利大于弊,獲得FDA的快速審批、優先審批、突破性藥物、孤兒藥四重地位,并在PDUFA前被批準上市,說明只要你的產品能解決目前的疑難雜癥,即使效果還不盡人意,你也不用擔心FDA的效率。反過來如果FDA成為你產品上市的障礙,你最好首先反思你那雞肋藥物是否值得浪費社會資源和對得起臨床實驗患者所冒的風險。

              Ofev同樣獲得FDA的快速審批、優先審批、突破性藥物、孤兒藥四重地位,更比PDUFA提前兩個半月批準上市(FDA這余地也留的大了點哈)。Ofev是多蛋白激酶抑制劑,至少抑制PDGF、FGF、VEGF受體。一個蛋白激酶抑制劑如果選擇性這么差,很可能還抑制和上述每個受體同族的其它蛋白激酶。Ofev顯然不是通過目前的一個靶點對應一個疾病的研發理念發現的。具體的發現過程我也沒有仔細查,但可以肯定這是一個動物模型驅動的研發項目而機理本身起的作用非常有限。Esbriet也同樣機理不清。對于IPF這樣病理未知的復雜疾病繞過機理顯然是個合理的策略。

              當然這兩個藥物的療效還相當輕微,并且不能用于重癥病人。Esbriet不能用于腎功能障礙患者,Ofev不能用于肝功能障礙患者。但這畢竟是個突破性進展,而且由于兩個藥物機理不同可能以后可以聯合使用。現在IPF的診斷也有進展,可望在發病前診斷,這樣更早期用藥可能效果更好。總之,今天IPF病人終于可以喘口氣了(both literally and metaphorically)。

              英文名 nintedanib

              中文名 寧特達尼

              Name Intedanib
              Synonyms Vargatef; BIBF 1120
              copyRight
              Molecular Structure CAS # 656247-17-5, Intedanib, Vargatef, BIBF 1120
              Molecular Formula C31H33N5O4
              Molecular Weight 539.62
              CAS Registry Number 656247-17-5

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