2014年12月21日讯 /生物谷BIOON/ --尽管遭到FDA专家委员拒绝，但FDA还是毫不犹豫的加速批准了阿斯利康的卵巢癌药物Lynparza（olaparib）。该药的获批，也标志着阿斯利康管线中新增了一枚重磅产品。就在前一天，Lynparza也获得了欧盟的批准。
具体而言，FDA已批准Lynparza用于既往经至少3次化疗治疗失败的BRCA胚系突变晚期卵巢癌患者的治疗。Lynparza（olaparib）是一种首创口服多聚ADP核糖聚合酶（PARP）抑制剂，利用DNA修复途径的缺陷，优先杀死癌细胞。目前，阿斯利康正开展多个III期研究，调查olaparib用于BRCA突变卵巢癌、胃癌、乳腺癌的治疗。
Lynparza通过FDA的加速审批程序批准，该药的获批是基于一项单组开放标签II期研究的数据及其他研究的安全性数据。该II期研究在137例既往经至少3次化疗失败的BRAC胚系突变晚期卵巢癌患者中开展，数据表明，olaparib维持疗法取得了34%的总缓解率（ORR），中位缓解持续时间为7.9个月。此前的一项研究表明，与安慰剂相比，olaparib显著延长了无进展生存期（PFS：11.2个月 vs 4.3个月，p＜0.00001）。
今年2月，阿斯利康根据一项II期临床数据向FDA提交了olaparib的监管文件，该研究评估了olaparib治疗铂类敏感性复发性高度浆液性卵巢癌的治疗。今年6月，FDA肿瘤药物顾问委员会（ODAC）以11:2的投票结果拒绝加速批准olaparib，并建议FDA等待阿斯利康正在开展的III期临床研究结果。今年7月，应FDA要求，阿斯利康提交了一份关于olaparib新药申请的重大修订，提供了额外数据支持了olaparib用于既往经至少3次化疗治疗失败的BRCA胚系突变卵巢癌患者的治疗。
目前，阿斯利康正在开展III期SOLO临床项目，FDA将对该项目的2个III期研究SOLO-2和SOLO-3进行全面审查，届时再决定是否将olaparib加速批准转为完全批准。SOLO-2研究正在调查olaparib作为一种维持疗法相对于安慰剂的疗效；SOLO-3研究正在调查治疗复发性卵巢癌时olaparib相对于标准化疗的疗效。SOLO-2研究的数据预计将在2015年获得，SOLO-3研究数据预计将在2019年获得。
今年早些时候，在拒绝辉瑞1140亿美元收购时，阿斯利康向投资者描绘了其肿瘤学管线的美好前景。阿斯利康对olaparib寄予厚望，认为该药的年销售额将突破20亿美元。不过，阿斯利康对肿瘤免疫疗法PD-L1抑制剂MEDI4736和另一种抗癌药AZD9291的期望更高，预测2者的年销售峰值分别为65亿美元和30亿美元，后者目前正处于I期临床。然而，这些产品要想实现预期目标，将取决于在一系列癌症中的临床成功。
另外，卵巢癌领域，FDA今年11月批准罗氏安维汀（Avastin）用于复发性卵巢癌。生物技术巨头安进研发的一款卵巢癌药物AMG-386已处于III期阶段。
关于BRCA基因：
BRCA1和BRCA2基因属于肿瘤抑制因子编码基因，这些基因的突变，与遗传性乳腺癌和卵巢癌相关。若一个女性继承了BRCA1或BRCA2突变，患乳腺癌和/或卵巢癌的风险将大大增加。在癌细胞扩增至卵巢以外之前，仅有15%的卵巢癌被发现。尽管当前治疗和诊断已经取得了很大进步，但癌细胞已扩散至卵巢外的患者，5年生存率低于50%。
关于Lynparza（olaparib）：
Olaparib是一种创新的、潜在首创口服多聚ADP核糖聚合酶（PARP）抑制剂，在临床前模型中已被证明，能够利用DNA修复途径的缺陷，优先杀死癌细胞。这种作用模式，赋予olaparib治疗具有DNA修复缺陷的广泛肿瘤类型的潜力。PARP与广泛的肿瘤类型相关，尤其是乳腺癌和卵巢癌。
英文原文：AstraZeneca grabs a surprise early approval for its $2B cancer contender
Despite loud objections from its advisers, the FDA granted an accelerated approval to AstraZeneca's ($AZN) ovarian cancer treatment, clearing an oral therapy the U.K. drugmaker believes will bring in blockbuster sales.
The drug, olaparib, is designed to treat advanced ovarian cancer in women with defective BRCA genes, and the FDA's approval covers patients who have already failed on three or more chemotherapy treatments. The nod comes just one day after the European Medicines Agency gave the drug its blessing, making olaparib the first poly ADP-ribose polymerase (PARP) inhibitor cleared in the U.S. AstraZeneca expects the treatment, to be marketed as Lynparza, to bring in $2 billion a year at its peak.
The FDA's approval is based on Phase II data in which the drug charted a 34% objective response rate for an average of 7.9 months. Treatment with olaparib also led to progression-free survival (PFS) of 11.2 months versus 4.3 months on placebo.
Those same results weren't enough to convince a panel of FDA advisers over the summer. In June, the agency's cancer drug committee picked apart olaparib's potential, taking issue with its failure to significantly improve overall survival, pointing to a few alarming adverse events and expressing doubts in the reliability of its PFS data. The group voted 11-2 against recommending an early approval for the drug, asking the agency to wait out AstraZeneca's ongoing Phase III study on olaparib before green-lighting it.
But AstraZeneca came back with additional information supporting the drug's use in thrice-failed patients who carry BRCA mutations, the FDA said, which was apparently enough to sway the agency's oncology division, affirming cancer chief Richard Pazdur's penchant for hurrying along new treatments that could change the standard of care.
Olaparib is approved alongside a companion diagnostic from Myriad Genetics ($MYGN) that can suss out which patients have the right genetic profile for the drug.
"Today's approval constitutes the first of a new class of drugs for treating ovarian cancer," Pazdur said in a statement. "Lynparza is approved for patients with specific abnormalities in the BRCA gene and is an example of how a greater understanding of the underlying mechanisms of disease can lead to targeted, more personalized treatment."
AstraZeneca unveiled its $2 billion expectation for olaparib earlier this year when the U.K. drugmaker was fending off unwelcome advances from Pfizer ($PFE). AstraZeneca has even higher hopes for MEDI4736, a PD-L1 therapy the company believes will top out at $6.5 billion a year; and AZD9291, a Phase I lung cancer treatment tabbed to peak at $3 billion.
For each of AstraZeneca's oncology contenders, reaching those lofty goals will depend on success across a range of cancers. For olaparib, the company is running concurrent Phase III trials in ovarian, gastric and breast cancers, hoping to win a string of approvals and cobble together a blockbuster.