Capivasertib

Positive high-level results from the DESTINY-Breast11 Phase III trial showed Enhertu (trastuzumab deruxtecan) followed by paclitaxel, trastuzumab and pertuzumab (THP) demonstrated a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) rate versus standard of care (dose-dense doxorubicin and cyclophosphamide followed by THP [ddAC-THP]) when used in the neoadjuvant setting (before surgery) in patients with high-risk, locally advanced HER2-positive early-stage breast cancer. Pathologic complete response is defined as no evidence of invasive cancer cells in the removed breast tissue and lymph nodes following treatment. The secondary endpoint of event-free survival (EFS) was not mature at the time of analysis; however, EFS data showed an early positive trend favouring Enhertu followed by THP compared to standard of care. The trial will continue to follow EFS. Approximately one in three patients with early-stage breast cancer are considered high risk, as they are more likely to experience disease recurrence and have a poor prognosis.1,2 Achieving pCR in early-stage HER2-positive breast cancer is associated with improved long-term outcomes.2,3 The current standard of care in many regions of the world in this neoadjuvant setting involves combination chemotherapy regimens.2 These regimens often include anthracyclines, which can be challenging for patients to tolerate and may result in long-term cardiovascular side effects.4 Further, nearly half of patients who receive neoadjuvant treatment do not achieve pCR, reinforcing the need for new treatment options.2,3 Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “The clinically meaningful improvement in pathologic complete response and the safety data seen in DESTINY-Breast11 highlight the potential of Enhertu to challenge the current standard of care in early-stage HER2-positive breast cancer. Enhertu is already an important treatment option in the metastatic setting, and these data have the potential to allow this medicine to move into early stages of disease where cure is possible.” Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “There are still many patients with early-stage breast cancer who do not achieve a pathologic complete response with treatment in the neoadjuvant setting, increasing the risk of disease recurrence. These topline results from DESTINY-Breast11 demonstrate that Enhertu followed by THP could offer patients with HER2-positive breast cancer a promising new treatment approach prior to surgery, setting more patients on a path towards a potential cure." Enhertu followed by THP showed an improved safety profile compared to ddAC-THP. The safety profiles of Enhertu and THP were consistent with the known profiles of each individual medicine with no new safety concerns identified. Rates of interstitial lung disease were similar across the Enhertu followed by THP and the ddAC-THP arms as determined by an independent adjudication committee. Following a recommendation by the Independent Data Monitoring Committee, patient enrolment in a third arm of the trial evaluating Enhertu alone was closed after a previous interim efficacy assessment of the trial arms. Data from DESTINY-Breast11 will be presented at an upcoming medical meeting and shared with regulatory authorities. Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. Enhertu has demonstrated improved outcomes in six Phase III breast cancer trials across different subtypes and stages of disease, including the recently announced DESTINY-Breast09 Phase III trial in the 1st-line HER2-positive metastatic setting. Enhertu is also being studied in several ongoing breast cancer trials including the DESTINY-Breast05 Phase III trial which is evaluating Enhertu in the high-risk adjuvant early HER2-positive setting. Notes HER2-positive early breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.5 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.5 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast cancer.6 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.7 Approximately one in five cases of breast cancer are considered HER2-positive.8 DESTINY-Breast11 DESTINY-Breast11 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of neoadjuvant Enhertu (5.4mg/kg) monotherapy or Enhertu followed by THP vs. the standard of care regimen in patients with high-risk (lymph node positive [N1-3] or primary tumour stage T3-4), locally advanced or inflammatory HER2-positive early-stage breast cancer. Patients were randomised 1:1:1 to receive either eight cycles of Enhertu monotherapy; four cycles of Enhertu followed by four cycles of THP; or four cycles of ddAC (dose-dense doxorubicin and cyclophosphamide) followed by four cycles of THP. The primary endpoint of DESTINY-Breast11 is pCR (absence of invasive disease in the breast and lymph nodes). Secondary endpoints include EFS, invasive disease-free survival, overall survival and safety. DESTINY-Breast11 enrolled 927 patients across multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov. Enhertu Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Enhertu (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC 3+ or in-situ hybridisation [ISH]+) breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial. Enhertu (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial. Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial. Enhertu (5.4mg/kg) is approved in more than 50 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu (6.4mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication will depend on whether a randomised controlled confirmatory clinical trial can demonstrate clinical benefit in this population. Enhertu (5.4mg/kg) is approved in the US and other countries for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on the results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication in the US is contingent upon verification and description of clinical benefit in a confirmatory trial. Enhertu development programme A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu as monotherapy or in combination or sequentially with other anti-cancer therapies across multiple HER2-targetable cancers. Daiichi Sankyo collaboration AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and Datroway (datopotamab deruxtecan) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway. AstraZeneca in breast cancer Driven by a growing understanding of breast cancer biology, AstraZeneca is challenging, and redefining, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death. AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. With Enhertu, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive, HER2-low and HER2-ultralow metastatic breast cancer, and are exploring its potential in earlier lines of treatment and in new breast cancer settings. In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap (capivasertib), the TROP2-directed ADC, Datroway (datopotamab deruxtecan), and next-generation oral SERD and potential new medicine camizestrant. PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease. AstraZeneca is also exploring the potential of saruparib, a potent and selective inhibitor of PARP1, in combination with camizestrant in BRCA-mutated, HR-positive, HER2-negative advanced breast cancer. To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is collaborating with Daiichi Sankyo to evaluate the potential of Datroway alone and in combination with immunotherapy Imfinzi (durvalumab). AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca. Contacts For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. References Matthew Bowden Company Secretary AstraZeneca PLC Oncology Corporate and financial

近日，阿斯利康公布了2025年第一季度财务业绩。报告显示，公司在总收入、核心盈利及研发管线推进方面均取得显著进展，为2030年实现800亿美元总收入的长期目标奠定了坚实基础。财务表现亮点：收入与盈利双增长2025年第一季度，阿斯利康实现总收入135.88亿美元，按实际汇率（Actual）同比增长7%，按固定汇率（CER）计算增长10%。这一增长主要由肿瘤学和生物制药业务的双位数增长驱动，且所有主要地区均实现收入增长。产品收入：135.14亿美元（同比增长7%，CER增长10%），其中：肿瘤学业务：56.43亿美元（CER增长13%），核心产品Tagrisso（16.79亿美元，CER+8%）和Imfinzi（12.61亿美元，CER+16%）表现突出。生物制药业务：56.31亿美元（CER增长12%），Farxiga（20.58亿美元，CER+16%）和呼吸领域药物Tezspire（2.17亿美元，CER+85%）贡献显著。罕见病业务：20.42亿美元（CER持平），Ultomiris（10.50亿美元，CER+25%）的增长部分抵消了Soliris（4.44亿美元，CER-38%）的专利到期影响。核心每股收益（EPS）：2.49美元，同比增长21%，反映运营效率提升和税率优化（核心税率16%，全年预期仍为18-22%）。研发里程碑：5项III期研究成功，13项全球获批第一季度，阿斯利康在创新管线上取得重大突破：关键III期研究结果：Enhertu（HER2阳性乳腺癌）：DESTINY-Breast09试验显示，联合疗法在一线治疗中显著改善无进展生存期（PFS）。Imfinzi（胃癌）：MATTERHORN试验达到无事件生存期（EFS）主要终点。camizestrant（HR+乳腺癌）：SERENA-6试验显示，针对ESR1突变患者的PFS显著改善。全球监管进展：Enhertu（欧盟）：获批用于HER2低表达/超低表达乳腺癌二线治疗。Imfinzi（美国、欧盟、中国）：新增肌层浸润性膀胱癌（NIAGARA）和早期非小细胞肺癌（AEGEAN）适应症。Truqap（中国）：获批联合氟维司群治疗PIK3CA/AKT1/PTEN突变乳腺癌。战略投资与区域扩张阿斯利康持续加码全球布局，尤其关注美国和中国市场：美国制造与研发：11个生产基地覆盖小分子、生物制剂和细胞疗法，计划进一步扩大在马里兰州和麻省的研发投入。中国战略：北京研发中心：新增第六个全球研发中心，聚焦早期研究和人工智能驱动的临床开发。合资企业：与BioKangtai合作建立疫苗生产基地，总投资约4亿美元。并购与合作：FibroGen中国业务：以1.6亿美元收购，获得罗沙司他在华权益。EsoBiotec：拟斥资10亿美元收购，拓展体内细胞疗法平台。中国调查进展与风险提示财报披露，阿斯利康正配合中国相关部门调查两项事宜：涉嫌未缴进口税款：涉及Enhertu，深圳海关初步认定未缴税款约160万美元，可能面临1-5倍罚款。个人信息收集问题：深圳公安已移交检察机关，公司声明未从中获利。可持续发展与ESG成果2024年，阿斯利康在环境和社会责任方面取得进展：碳排放：范围1和2排放较2015年减少77.5%，63%车队实现电动化。健康公平：通过“健康心脏非洲”等项目覆盖超9000万人，获CDP气候评级“A”级。2025年财务指引公司重申全年预期：总收入：按CER计算，预计实现高个位数增长。核心EPS：低双位数增长。汇率影响：若2025年4-12月汇率维持3月水平，总收入与核心EPS将面临低个位数负面影响。管理层评论首席执行官苏博科（Pascal Soriot）表示：“2025年的强劲开局印证了我们的增长战略和管线执行力。随着Enhertu、Imfinzi等重磅产品的数据公布和获批，阿斯利康正迈向2030年800亿美元收入的目标。我们尤其看好美国和中国市场的长期潜力，并将通过持续投资巩固领先地位。药事纵横投稿须知：稿费已上调，欢迎投稿