2014年10月15日訊 /生物谷BIOON/ --導讀：輝瑞（Pfizer）突破性乳腺癌藥物palbociclib備受業界關注，業界此前預測，如果獲批，該藥年銷售峰值將突破30億美元，在《即將結束臨床試驗的全球重磅藥物TOP 15》榜單中位列第四。此前，FDA已授予palbociclib突破性療法認定，而輝瑞於2014年8月提交上市申請。近日，該藥在監管方面傳來了好消息。
FDA將優先審查palbociclib
輝瑞（Pfizer）近日宣布，FDA已接受審查palbociclib新藥申請（NDA），同時已授予優先審查資格（Priority Review Status），並已指定處方藥用戶收費法（PDUFA）目標日期為2015年4月13日。優先審查資格意味著FDA將在6個月內完成palbociclib NDA的審查，相比常規的10個月審查周期縮短了4個月。如果獲批，palbociclib+曲唑（letrozole）聯合療法作為ER+/HER2-晚期乳腺癌的一線療法，將為成千上萬轉移性乳腺癌患者提供一個重要的新選擇。
palbociclib獲批機會很大
此前，有學者對已獲得優先審查資格的藥物的歷史批准率進行了統計，發現了一個有趣的數據：獲得優先審查資格的藥物，第一輪批准率為67.9%（72/106）；而標準審查的藥物中，這一數據僅為40.3%（79/196）。因此，有分析師預計，palbociclib有很大的機會能獲得FDA的批准。
近幾年來，輝瑞一直受困於稀疏的研發管線，極度渴望收穫幾個重磅產品重振雄風。此次，輝瑞決定奮力一搏，僅根據II期臨床試驗數據便提交palbociclib上市申請。而競爭對手諾華（Novartis）已於去年11月將其CDK4/6抑制劑LEE011推進至III期研究，預計在2016年提交上市申請，而禮來（Eli Lilly）的CDK4/6抑制劑LY2835219的推進相對緩慢，研究進程落後於輝瑞和諾華，目前也已進入III期，預計將在2017年提交上市申請。
輝瑞或率先撬開CDK4/6市場
如果輝瑞這一大膽策略獲得成功，palbociclib將率先撬開CDK4/6抑制劑市場，LEE011和LY2835219則只能尾隨其後，該類藥物將為乳腺癌的臨床治療帶來重大進步。
palbociclib是一種CDK4/6抑制劑，能夠選擇性抑制細胞周期蛋白依賴性激酶4和6（CDK4/6），恢復細胞周期控制，阻斷腫瘤細胞增殖。此前，FDA已於2013年4月授予palbociclib突破性療法，輝瑞於2014年8月向FDA提交了上市申請，尋求批准用於雌激素受體陽性（ER+）、人表皮生長因子受體2陰性（HER2-）晚期乳腺癌的一線治療。
palbociclib NDA的提交，是基於II期PALOMA-1研究的喜人結果。數據表明，與標準治療藥物曲唑（letrozole）治療組相比，palbociclib+曲唑聯合用藥組疾病無進展生存期（PFS）取得了統計學意義的顯著延長（20.2個月vs 10.2個月，p=0.0004），達到了研究的主要終點。
細胞周期失控是癌症的一個標誌性特徵，CDK4/6在許多癌症中均過度活躍，導致細胞增殖失控。CDK4/6是細胞周期的關鍵調節因子，能夠觸發細胞周期從生長期（G1期）向DNA複製期（S1期）轉變。在雌激素受體陽性（ER+）乳腺癌（BC）中，CDK4/6的過度活躍非常頻繁，而CDK4/6是ER信號的關鍵下遊靶標。臨床前數據表明，CDK4/6和ER信號雙重抑制具有協同作用，並能夠抑制G1期ER+BC細胞的生長。（生物谷Bioon.com）
英文原文：Pfizer nabs a fast FDA review for breast cancer pipeline star palbociclib
Pfizer ($PFE) has picked up a priority review designation for its closely watched cancer drug palbociclib, potentially slicing four months off the review timeline for a therapy that is being hustled along at an accelerated rate.
The pharma giant, which has been plagued by a thin pipeline after undergoing major R&D deconstructive surgery in recent years, has a lot riding on this one. Pfizer decided to lunge for an approval for palbociclib on Phase II data at the urging of a number of analysts excited by the blockbuster potential of this drug. Peak sales estimates typically range around $3 billion a year--which would be a big boost to Pfizer.
The CDK 4/6 inhibitor has already won breakthrough drug status at the FDA. The PDUFA date for palbociclib will fall on April 13, 2015, as Pfizer seeks an OK to market it for women with advanced or metastatic ER+, HER2- breast cancer.
Pfizer is racing to an approval in hopes of gaining a head start on Novartis ($NVS) and Eli Lilly ($LLY), both of which have their own CDK drugs in the late-stage pipeline. LEE011 from Novartis should be ready in 2016 and Lilly may file bemaciclib a year later.
Back in the spring Pfizer reported that the drug doubled the average amount of progression-free survival (PFS) time among patients with advanced breast cancer. But in the first detailed glimpse of its impact on overall survival (OS)--a key feature to the future prospects of this flagship program--the therapy had so far failed to demonstrate a statistically significant improvement in extending patients' lives after an initial assessment.
"This acceptance has been expected and clears some of the risks of the program as some investors started to consider the scenario in which phase 3 results would be needed," noted ISI analyst Mark Schoenebaum, who's followed the drug closely.
Adds the analyst: "An interesting data point from the academic literature about historical approval rates for FDA filings that were granted priority review status: first-cycle approval rates were 72 of 106 (67.9%) for applications granted a priority review and 79 of 196 (40.3%) for drugs given a standard review."
"If approved as a first-line therapy in combination with letrozole, palbociclib will be an important new option for the thousands of women in the U.S. who are living with metastatic breast cancer," said Garry Nicholson, president, Pfizer Oncology. "We look forward to continuing to work closely with the FDA through the review process."