美国生物医药公司Puma Biotechnology在今年夏天可谓红极一时。今年7月，该公司宣布乳腺癌药物neratinib关键III期临床研究（ExteNET）顶线结果，数据表明，在用于治疗早期HER2阳性乳腺癌时，neratinib疗效超越罗氏重磅药物赫赛汀（Herceptin）。消息发布后，Puma股价翻了三番，该公司创始人兼CEO Alan Auerbach随即成为新晋亿万富翁。
然而近日，Puma突然宣布将neratinib上市申请时间推迟1年。消息发布后，因投资者出现忧虑情绪，Puma股价应声暴跌20%。Puma表示公司原计划于2015年上半年向FDA提交neratinib上市申请。但经过与FDA会晤，Puma被告知需要同时提交临床前致癌性研究数据以及关键临床数据用于支持neratinib的新药申请。Puma表示，为满足FDA的这一要求，公司计划将neratinib监管计划推迟至2016年第一季度。
其实，在此之前，neratinib已经表现出了一些令人不安的信号。今年11月，Puma公布了另一项II期研究（NEFERTT）数据。该研究将neratinib+紫杉醇作为一线疗法与赫赛汀+紫杉醇进行了比较。数据显示，neratinib未能改善复发性乳腺癌的无进展生存期（PFS）。Puma表示，预计该研究不能达到主要终点，不过该公司强调，neratinib达到了阻止癌症扩散至中枢神经系统的次要终点，并宣称这是首次HER2靶向疗法显示出抑制中枢神经转移疗效，意义重大。而投资者认为这是强词夺理，Puma股价随即下跌8%。
回到今年7月，在III期（ExteNET）研究中，2812例已接受手术和赫赛汀辅助治疗的早期HER2阳性乳腺癌患者，随机分配至为期一年的neratinib或安慰剂辅助治疗。数据表明，与安慰剂相比，neratinib使无病生存期改善33%。该数据令业界震惊，neratinib也瞬间成为了行业关注的焦点。行业分析师纷纷预测，neratinib将成为年销售峰值达10亿美元的重磅药物。而Puma原计划根据该研究数据于2015年初第一季度向FDA提交neratinib监管申请，寻求批准用于扩展期辅助治疗。
本周二，Puma CEO Auerbach在电话会议上指出，在FDA要求提交致癌性研究数据时，公司本认为能够在2015年11月完成提交，但FDA却告知所有结果需要在同一时间被提交，因此不得不将原计划推迟。不过，Auerbach认为，neratinib监管申请的推迟，不会影响该公司的长期前景。
关于neratinib：
neratinib是一种口服、不可逆、泛ErbB受体酪氨酸激酶抑制剂，能有效抑制ErbB1和ErbB2，其作用机制与罗氏赫赛汀（曲妥珠单抗）及乳腺癌新药Perjeta（帕妥珠单抗）不同，后2者为单克隆抗体药物，靶向于HER2阳性癌细胞表面的HER2受体。Perjeta联合Herceptin及多西紫杉醇化疗被认为能够对HER2信号传导通路提供更全面的封锁。
英文原文：Puma tanks on a fresh setback for its breast cancer drug
Puma Biotechnologies ($PBYI) is walking back some bullish prognostications for its breast cancer treatment, delaying its planned FDA submission by as much as a year and lending weight to some creeping doubts about its top prospect.
Over the summer, after announcing positive late-stage data on neratinib, Puma said it was on track to file the HER2-targeting breast cancer treatment in the first half of next year. Now, however, the company has altered its desired indication from treating HER2-positive breast cancer that has already spread to serving as a follow-on therapy for patients with early stage breast cancer, Puma said. And, after meeting with the FDA, the company has learned that it'll need to submit results from preclinical carcinogenicity studies alongside its pivotal data to support its new goal, a process that will delay neratinib's filing until the first quarter of 2016, Puma said.
The revelation sent Puma's shares down by as much as 20% after hours on Tuesday, as investors took the last-minute change in strategy as a troubling sign for a drug that has lost some luster over the past few months.
In November, neratinib failed to better extend progression-free survival (PFS) when pitted against Roche's ($RHHBY) Herceptin in a Phase II study. Puma said it expected the drug to flunk its primary endpoint all along, taking care to point out that neratinib did hit its secondary goal of preventing the spread of cancer to the central nervous system.
Puma's drug rocketed into the spotlight back in June when the biotech posted Phase III results in which neratinib, delivered as an adjuvant to Herceptin, contributed to a 33% improvement in PFS. The company's shares promptly tripled in value, spurring peak sales projections north of $1 billion.
Those data convinced Puma to amend its desired indication for neratinib, CEO Alan Auerbach said on a conference call Tuesday. At the time, the company believed it could submit the requisite carcinogenicity studies, slated to wrap up in November 2015, after filing the drug, Auerbach said. But regulators have since informed Puma that all results need to be handed in at the same time, he said.
However, Auerbach believes the resulting delay will have no effect on Puma's long-term prospects of finding a partner for neratinib or landing a buyout deal, he told analysts.
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