阿斯利康抗癌药olaparib上市之路坎坷不平

最近辉瑞报价收购阿斯利康的消息在生物医药领域引起巨大反响，而阿斯利康公司反对收购的一项重要武器就是其正处于报批过程中的治疗卵巢癌药物olaparib。阿斯利康公司以此说服投资者，公司有能力独自研制重大药物。阿斯利康CEO Pascal Soriot对这一药物寄予厚望，表示一旦上市其销售额最高可达20亿美元。然而FDA的专家并不像他如此乐观。最近FDA的相关专家对这一药物提出了质疑。原因之一在于阿斯利康在进行临床研究过程中招募BRCA基因突变患者的群体过小，所提供数据无法充分说明其药效。同时考虑到其潜在副作用，FDA的专家可能会希望FDA在阿斯利康公司提供进一步详细说明数据前暂缓批准olaparib上市。毫无疑问这一结果可能也会使阿斯利康的投资者感到失望。

详细英文报道：

AstraZeneca's ($AZN) reconstructed case for the cancer drug olaparib is built on the fundamental premise that the new management team at the pharma giant is a whole lot smarter than the old crew. After a retrospective analysis found a subgroup response in the data for ovarian cancer, CEO Pascal Soriot not only ordered the team to renew its pursuit of an approval, he later assigned a $2 billion peak sales value to the program.

Inside investigators at the FDA, though, have raised some serious criticism of the data that were submitted with the application to market the drug as a maintenance therapy for patients with an hereditary BRCA mutation. Two days ahead of an external panel review, the FDA review questions whether the conclusions AstraZeneca reached could have been skewed by a very small group of patients delivering signs of a false benefit due to an "underperforming" control arm in the study. And given the potential side effects, the agency wants the reviewers to consider whether AstraZeneca should wait on more definitive data before marketing a drug that could just be adding to patients' woes.

"The small sample size of gBRCAm patients and the retrospective identification of this patient population call into question the reliability of the estimation of treatment effect," states the review. "The retrospective identification of the gBRCAm population did not appear to result in gross imbalances of known prognostic factors that could account for the treatment effect seen in Study 19, but it is important to note that the loss of randomization and the selection of a convenient sample of patients who had available whole blood sample for retrospective testing may have led inadvertently to an unequal distribution of unknown factors that may have affected the study results. The hazard ratio of 0.17 certainly suggests that most patients will have some degree of prolongation of PFS from treatment, but the data demonstrating that the placebo-treated gBRCAm performed more poorly in terms of PFS when compared to the placebo-treated gBRCAwt/vus raise the concern that the median improvement of seven months may be due in part to an "underperforming" control arm. The analysis of overall survival suggests no detriment as a result of therapy, but no survival difference was seen between treatment arms."

A setback here would raise more questions about the judgment of AstraZeneca's management group, which badly needs to demonstrate that it can efficiently develop important new drugs. Olaparib had been a significant part of Soriot's case against Pfizer's failed $120 billion takeover bid, offering proof of the bright future that lies ahead of the pharma giant now that an R&D turnaround has taken place. And the CEO has expressed supreme confidence that AstraZeneca made the right decision in reviving hopes for this drug.

"When I saw olaparib, for me, it was a clear reflection of good science and poor management ...," Soriot told Forbes' Matthew Herper recently. "Essentially, the commercial teams were under-excited."

A positive vote this week will help Soriot. But a thumb's down may remind investors of AstraZeneca's woeful past and revive speculation that a new Pfizer ($PFE) bid may yet be in the offing.