阿斯利康启动olaparib III期SOLO项目

2013年9月4日讯 /生物谷BIOON/ --阿斯利康（AstraZeneca）9月4日宣布，启动抗癌药olaparib的III期SOLO项目，旨在调查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疾病无进展生存期（PFS）利益。Olaparib是一种创新的口服多聚ADP核糖聚合酶（PARP）抑制剂，目前正调查用于BRCA突变卵巢癌的治疗。

业界此前普遍认为，olaparib上市的机会不大，但随着近期的测试分析，业界对该药前景的信心已经恢复。

2011年12月，阿斯利康决定不再推进olaparib至III期临床开发，并由此产生了2.85亿美元税前减损费用。随着III期SOLO项目的启动，该笔资产将回转至阿斯利康2013年第三季度资产负债表。

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。

III期SOLO项目包含2个研究：SOLO 1研究正与妇科肿瘤学组（Gynecologic Oncology Group，GOG）合作开展，调查olaparib作为一种单药疗法，用于携带BRCA突变卵巢癌患者一线铂为基础的化疗后维持治疗的利益；SOLO 2研究与妇科肿瘤试验组欧洲网络（European Network of Gynaecological Oncological Trial Groups，ENGOT）合作开展，调查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治疗的利益，这2项试验均为随机、双盲、安慰剂对照研究，研究中使用的是olaparib片剂，给药剂量为每天2次300mg，主要终点均为疾病无进展生存期（PFS）。

Myriad Genetics公司将为III期SOLO项目提供olaparib伴侣诊断试剂盒，来检测BRCA突变。

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。

英文原文阅读

AstraZeneca initiates Phase III clinical programme for olaparib, a treatment in development for patients with BRCA mutated ovarian cancer

Wednesday, 4 September 2013

As a result of the initiation of this programme, a pre-tax impairment charge of $285 million will be reversed and the asset restored to our balance sheet in the third quarter of 2013. The reversal of this impairment charge will be excluded from core earnings.

AstraZeneca today announced enrollment of the first patient in the Phase III clinical programme for olaparib, an innovative oral poly ADP ribose polymerase (PARP) inhibitor being investigated for the treatment of BRCA mutated ovarian cancer. The Phase III SOLO (Study of OLaparib in Ovarian cancer) programme is designed to determine the benefit, by progression free survival, of olaparib as a maintenance monotherapy in BRCA mutated ovarian cancer patients who are in complete or partial response following platinum-based chemotherapy in the first line setting (SOLO 1), and in the relapsed setting (SOLO 2).

The SOLO 1 study is being conducted in collaboration with the Gynecologic Oncology Group and the SOLO 2 study with the European Network of Gynaecological Oncological Trial Groups. Both trials are randomised, double blind, placebo controlled studies that utilise the tablet formulation of olaparib at a dose of 300mg twice daily.

The initiation of these studies is based on the subgroup analysis by BRCA mutation status of the Phase II maintenance study in relapsed ovarian cancer, announced at the American Society of Clinical Oncology (ASCO) 2013 Congress, which demonstrated olaparib’s potential as a maintenance treatment for platinum-sensitive relapsed patients with BRCA mutated ovarian cancer.

As a result of the initiation of this programme, the pre-tax impairment charge of $285 million, which was incurred in December 2011 following the decision not to progress olaparib into phase III development, will be reversed in the third quarter of 2013. The reversal of this impairment charge will be excluded from Core earnings per share.

Antoine Yver, Vice President and Head of Oncology in AstraZeneca’s Global Medicines Development unit said: “This is a significant milestone for olaparib, and further evidence of AstraZeneca’s commitment to invest in distinctive science in our core therapy areas, with a particular focus on high unmet need. We feel olaparib has real potential to significantly improve treatment decisions for this group of patients who currently have limited options, and to become the next important product in our growing oncology portfolio.”

BRCA1 and BRCA2 are human genes that belong to a type of genes known as tumour suppressors. Mutation of these genes has been linked to hereditary breast and ovarian cancer and a woman's risk of developing breast and/or ovarian cancer is greatly increased if she inherits a BRCA1 or BRCA2 mutation. Only 15 per cent of ovarian cancers are found before the cancer has spread outside the ovary. Despite advances in treatment and diagnosis, for patients with ovarian cancer that has spread beyond the ovary the five-year survival rate is well below 50 per cent.

NOTES TO EDITORS

About the SOLO 1 trial

The SOLO 1 trial looks at olaparib as a maintenance monotherapy in patients with BRCA mutated ovarian cancer following first line platinum based chemotherapy. The aim of the trial is to determine the benefit of olaparib maintenance monotherapy (compared to placebo) in patients with BRCA mutated high risk ovarian cancer who are in clinical complete response or partial response following first line platinum based chemotherapy, by assessment of progression free survival. Patients must have completed first line platinum based chemotherapy to qualify for the trial. SOLO 1 (GOG-3004) is in collaboration with the Gynecologic Oncology Group. More details can be found at ClinicalTrials.gov (identifier: NCT01844986).

About the SOLO 2 trial

The SOLO 2 trial looks at olaparib as a maintenance monotherapy in patients with BRCA mutated platinum sensitive relapsed ovarian cancer. The aim of the trial is to determine the benefit of olaparib maintenance monotherapy (compared to placebo) in patients with BRCA mutated relapsed ovarian cancer that are in complete or partial response following platinum based chemotherapy, by assessment of progression free survival. Patients must have completed at least two lines of platinum based chemotherapy to qualify for the trail. SOLO 2 (ENGOT-Ov21) is in collaboration with the European Network of Gynaecological Oncological Trial Groups. More details can be found at ClinicalTrials.gov (identifier: NCT01874353).

About olaparib

Olaparib is an innovative, potential first-in-class oral poly ADP ribose polymerase (PARP) inhibitor that has been shown in pre-clinical models to exploit DNA repair pathway deficiencies to preferentially kill cancer cells. This mode of action gives olaparib the potential for activity in a range of tumour types with DNA repair deficiencies. PARP is associated with a range of tumour types, in particular with breast and ovarian cancers.

The Phase III SOLO studies follow the announcement at the American Society of Clinical Oncology (ASCO) 2013 Congress of the subgroup analysis of the Phase II study of olaparib maintenance treatment in platinum-sensitive relapsed ovarian cancer patients, which identified patients with BRCA mutated ovarian cancer as the population receiving the greatest treatment benefit from olaparib maintenance therapy, significantly prolonging progression free survival compared with placebo (progression free survival HR 0.18; 95% CI 0.11-0.31; p<0.00001, median progression free survival 11.2 vs 4.3 months in favour of the group of patients with BRCAm disease).