FDA授予阿斯利康抗癌药olaparib优先审查资格

关键词:卵巢癌,阿斯利康,olaparib,BRCA突变

 

2014年5月2日讯 /生物谷BIOON/ --阿斯利康(AstraZeneca)5月1日宣布,FDA已授予抗癌药奥拉帕尼(olaparib)新药申请(NDA)优先审查资格。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。如果获批,olaparib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 NDA的提交,是基于II期Study-19研究的数据。Study-19是一项随机、双盲、安慰剂对照II期研究,在既往接受过至少2种铂化疗方案、且最后一次铂化疗方案后处于部分或完全缓解的铂敏感复发性浆液性卵巢癌患者中开展,评估了olaparib 400mg BID(每日2次)作为一种维持疗法,相对于安慰剂的疗效和安全性。研究的主要终点是疾病无进展生存期(PFS),次要终点包括癌症复发的时间、总生存期合安全性。

此外,欧洲药品管理局(EMA)于2013年9月接收审查olaparib的上市许可申请(MAA)。同时,阿斯利康于2013年9月启动了olaparib的III期SOLO项目,调查olaparib作为一种单药疗法,用于携带BRCA突变铂敏感卵巢癌患者维持治疗的无进展生存期(PFS)利益。

III期SOLO项目的启动,是基于对复发性卵巢癌患者中开展的II期维持研究中患者BRCA突变状态的亚组分析结果,相关数据已提交至美国临床肿瘤学会(ASCO)2013年会,证明了olaparib作为一种单药疗法,用于携带BRCA突变的铂敏感复发性卵巢癌患者维持性治疗的潜力。亚组分析鉴定出,携带BRCA突变的卵巢癌患者,从olaparib单药维持疗法中获得了最大的治疗益处,与安慰剂相比,olaparib显著延长了携带BRCA突变卵巢癌患者的无进展生存期(PFS)(11.2个月 vs 4.3个月,HR 0.18; 95% CI 0.11-0.31; p<0.00001)。

该发现,强调了抗癌药物开发过程中日益注重的本质,即针对特定亚组患者的基因档案。

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。(生物谷Bioon.com)

英文原文:US FDA grants priority review for AstraZeneca's ovarian cancer drug olaparib

The US Food and Drug Administration has granted Priority Review for Anglo-Swedish drug major AstraZeneca’s (LSE: AZN) olaparib for ovarian cancer.

The drug is an oral poly ADP-ribose polymerase (PARP) inhibitor that exploits DNA repair pathway deficiencies to preferentially kill cancer cells. It is being reviewed in ovarian cancer patients who have a BRCA mutation and whose cancer has relapsed following a complete or partial response to platinum-based chemotherapy. Patients with the BRCA mutation are being identified through a companion diagnostic test.

The Priority Review status means that the FDA intends to take action on the olaparib application within six months (compared to 10 months under standard review, with a Prescription Drug User Fee Act (PDUFA) date of October 3.

The NDA filing was based on Phase II study 19 data, a randomized, double-blind, placebo-controlled, Phase II study, which evaluated maintenance treatment with olaparib 400 mg twice daily versus placebo in platinum-sensitive relapsed serous ovarian cancer patients who had received previous treatment with at least two platinum regimens and were in a maintained partial or complete response following their last platinum regimen. The primary endpoint was progression-free survival by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Secondary endpoints included time to progression by cancer antigen-125 (Gynecologic Cancer Intergroup criteria) or RECIST, overall survival and safety.

Also potential for European approval

Lisa Anson, president of AstraZeneca UK and Ireland, said: “AstraZeneca has a strong commitment to cancer as a core therapy area and the decision by the FDA to grant priority review for olaparib – a drug discovered here in the UK - highlights the exciting science behind this potential first-in-class medicine. We continue to work closely with NICE and the NHS to ensure that ovarian cancer patients in the UK can benefit from this treatment should it be approved in Europe.”

In September, AstraZeneca announced that the European Medicines Agency accepted its Marketing Authorisation Application for olaparib. If approved by regulatory authorities, olaparib would be the first PARP inhibitor for patients with BRCA mutated platinum-sensitive relapsed ovarian cancer.

(责任编辑:lishuheng)

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