今年6月底，阿斯利康（AZN）“死而复生”的抗癌药Lynparza（olaparib）被FDA专家委员会否决。近日，该药在欧盟却收获了好消息。欧洲药品管理局（EMA）人用医药产品委员会（CHMP）支持加速批准olaparib，作为一种单药疗法，用于铂敏感复发性BRCA突变卵巢癌成人患者的维持治疗。EMA通常都会采纳CHMP的意见，这也意味着olaparib将在3个月内获批，该药也将成为用于BRCA突变铂敏感复发性卵巢癌的首个PARP抑制剂。
Olaparib是一种创新的口服多聚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，阿斯利康正在调查olaparib用于BRCA突变卵巢癌的治疗。
CHMP的积极意见，是基于一项II期临床研究（Study 191）的数据。该研究在携带BRCA突变卵巢癌患者中开展，数据表明，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）。然而，这一数据在今年6月却遭到FDA专家委员会的百般挑剔，FDA专家认为，olaparib并没有改善总生存期（OS），研究中也发生了几个令人担忧的不良事件，同时对PFS数据的可靠性表示怀疑，因此拒绝加速审批olaparib，同时要求阿斯利康必须完成正在开展的III期研究，FDA将于2015年1月作出审查决定。
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，阿斯利康对抗癌免疫疗法PD-L1抑制剂MEDI4736和另一种抗癌药AZD9291的期望更高，并预测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。对于olaparib而言，阿斯利康正在开展多个III期临床，评价该药用于卵巢癌、胃癌、乳腺癌的治疗。
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 gets some EU encouragement for its $2B cancer hopeful
European regulators have recommended an early approval for AstraZeneca's ($AZN) new ovarian cancer treatment, welcome news for the company as it defends rosy sales estimates for its oncology pipeline.
The European Medicines Agency has voted in favor of the AstraZeneca's olaparib, which would sell as Lynparza. The group's recommendation is generally followed by a full continental approval in about three months, a move that would clear the drug for the treatment of patients with platinum-sensitive ovarian cancer and BRCA mutations.
The EMA's vote is based on a Phase II trial in which olaparib led to progression-free survival (PFS) of 11.2 months versus 4.3 months on placebo, data that weren't enough to sway U.S. regulators considering an early approval of their own.
Over the summer, AstraZeneca presented the same results to a panel of FDA experts, and the group picked apart olaparib's potential, taking issue with the 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 committee voted 11-2 against recommending an early approval for the drug, meaning AstraZeneca will likely have to complete its ongoing Phase III study on olaparib before it can make its way to the U.S. market.
The company maintains that olaparib, a PARP inhibitor, can eventually bring in $2 billion a year in sales, a figure unveiled earlier this year as the U.K. drugmaker worked to fend off unwelcome advances from Pfizer ($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.
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