Pertuzumab

关注并星标CPHI制药在线近日，多家跨国巨头（MNC）发布今年一季度财报，在诸多压力和多变市场格局的裹挟下，MNC们的业绩继续出现分化，不过，肿瘤领域仍是大部分MNC的基本盘。那么，今年第一季度，MNC的肿瘤业绩走向如何？默沙东默沙东今年一季度全球销售额为155亿美元，同比下降2%。制药业务收入136.38亿美元（占比88%），同比下降3%，主要受疫苗和抗病毒产品下滑拖累。尽管业绩出现波动，但肿瘤领域实现增长，核心产品PD-1抑制剂K药（Keytruda，帕博利珠单抗）表现依旧亮眼。K药一季度销售额为72.05亿美元，同比增长4%，占整个制药业务的53%。在美国市场，K药的业绩增长主要得益于非小细胞肺癌（NSCLC）的辅助/新辅助治疗，以及晚期尿路上皮癌适应症；而在美国之外的市场，K药的增长主要得益于三阴性乳腺癌（TNBC）、肾癌的辅助/新辅助治疗，以及转移适应症的需求。事实上自从2021年开始，辅助/新辅助治疗的肿瘤早期适应症已成为PD-1的新战场。在TNBC的辅助/新辅助治疗临床中，K药展现出了惊艳的效果。KEYNOTE-522研究结果显示，中位随访39.1个月，K药+化疗组较单纯化疗组取得EFS（无事件生存期）显著改善，HR=0.63（95%CI 0.48～0.82，P=0.00031）。基于该研究优异表现，FDA和欧洲药品管理局（EMA）以及NMPA，均批准帕博利珠单抗联合化疗应用于高危早期TNBC的新辅助治疗及后续辅助治疗。在NSCLC领域，K药效果同样突出。根据III期KEYNOTE-091试验数据，在手术切除后接受铂类辅助化疗的患者中，与安慰剂组相比，K药能够减少患者疾病复发或死亡风险达27%。在其主要终点无疾病生存期（DFS）方面，K药组患者的中位DFS为58.7个月，而安慰剂组患者则仅为23.8个月。默沙东曾预计到2028年，K药辅助/新辅助治疗适应症相关销售额占比能达到30%，可见早期癌症治疗领域的巨大潜力。其他抗肿瘤药物，默沙东的口服低氧诱导因子2α（HIF-2α）抑制剂Welireg（belzutifan）于今年2月19日获欧盟批准，用于治疗von Hippel-Lindau（VHL）病相关肿瘤，是首个获批上市的HIF-2α抑制剂，此前已在美国、英国、加拿大等多个国家和地区获得批准。一季度，Welireg销售额为1.37亿美元，同比增长62%。另外，默沙东与阿斯利康联合开发的PARP抑制剂Lynparza（奥拉帕利）、与日本卫材合作的Lenvima（仑伐替尼）、与BMS合作开发的Reblozyl（罗特 西普）分别为默沙东带来了3.21、2.58、1.19亿美元的收入。在新进展方面，K药联合疗法用于局部晚期头颈鳞癌的围手术期治疗已获FDA优先审评，PDUFA日期为2025年6月23日。另外默沙东的皮下注射版K药的III期试验已在一季度公布了首批数据，结果显示，皮下注射K药联合透明质酸酶α（MK-3475A）在转移性NSCLC一线治疗中，其疗效和安全性不劣于静脉注射剂型，PDUFA目标日期为2025年9月23日。默沙东的 ROR1 ADC新药Zilovertamab Vedotin已启动针对弥漫大B细胞淋巴瘤的III期试验。该药是默沙东于2020年，以27.5亿美元收购VelosBio公司所得。罗氏罗氏2025年一季度营收 154.40 亿瑞士法郎，同比增长6%，制药部门营收达到 119.49 亿瑞士法郎，同比增长8%。肿瘤领域营收同比增长2%， 其中HER2 产品组合（Phesgo、Perjeta 和 Kadcyla）和阿替利珠单抗（Tecentriq）贡献了主要业绩。Phesgo是由曲妥珠单抗+帕妥珠单抗和透明质酸酶构成的一种复方制剂皮下注射液，用于治疗早期和转移性HER2+乳腺癌。与传统静脉给药相比，Phesgo的给药时间缩短了90-95% （由原来150分钟降低至5分钟），大大提高了患者依从性。今年一季度，Phesgo销售额为5.93亿瑞士法郎，同比增长52%。Perjeta（帕妥珠单抗）是一款靶向HER2的重组人源化单抗，用于联合曲妥珠单抗和化疗辅助治疗HER2+早期乳腺癌、新辅助治疗HER2+局部晚期、炎性或早期乳腺癌患者（直径>2cm或淋巴结阳性），以及用于HER2+、转移性或不可切除的局部复发性乳腺癌等。一季度，Perjeta销售额为8.4亿瑞士法郎，同比减少10%。Kadcyla（恩美曲妥珠单抗）是一种靶向HER2 的ADC，由人源化IgG1曲妥珠单抗，通过MCC连接子，与DM1偶联而成，用于早期和转移性HER2+乳腺癌的二线治疗、辅助治疗等。一季度，Kadcyla销售额为5.06亿瑞士法郎，同比增长5%。Tecentriq是一款靶向PD-L1的单克隆抗体，目前，已在全球范围内获批用于治疗非小细胞肺癌（NSCLC）、小细胞肺癌（SCLC）、肝细胞癌、尿路上皮癌、PD-L1阳性转移性TNBC和BRAF V600突变的晚期黑色素瘤等多种癌症。一季度，Tecentriq营收8.7亿瑞士法郎，同比无变化。管线进展方面，罗氏启动了TIGIT单抗tiragolumab联合Tecentriq治疗局部晚期食管癌的III期研究。阿斯利康一季度，阿斯利康总营收135.88亿美元，同比增长10%。肿瘤领域业绩主要由Tagrisso（奥希替尼）、Imfinzi（度伐利尤单抗）、Enhertu（德曲妥珠单抗）等贡献。Tagrisso是第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），能够高效抑制EGFR敏感突变（如19号外显子缺失、L858R）及耐药突变（如T790M），并具备较强的血脑屏障穿透能力，而且是全球首个获批的第三代EGFR-TKI，因此，Tagrisso是三代EGFR-TKI的标杆药物。目前Tagrisso的适应症覆盖肺癌全周期治疗（一线、二线及辅助治疗）。今年一季度，Tagrisso营收16.79亿美元，同比增长8%。Imfinzi是一种PD-L1抑制剂，通过阻断肿瘤细胞表面的PD-L1与T细胞PD-1受体结合，解除免疫抑制信号，激活T细胞对癌细胞的杀伤作用。Imfinzi已在NSCLC、胆道癌等领域建立围手术期免疫治疗标杆，并于今年3月获FDA批准，联合吉西他滨与顺铂，用于肌层浸润性膀胱癌（MIBC）成人患者的围手术期治疗。一季度，Imfinzi营收12.61亿美元，同比增长16%。Enhertu（HER2-ADC）是第一三共/阿斯利康的明星产品，目前已获批用于HER2+乳腺癌二线治疗、HER2低表达乳腺癌、局部晚期或转移性HER2+胃或胃食管结合部腺癌、局部晚期或转移性NSCLC等。一季度，叠加第一三共负责的地区销售额，Enhertu全球销售额为10.86亿美元。Lynparza（奥拉帕利）是一种FIC的PARP抑制剂，也是首个合成致死靶向治疗药物，用于靶向带有同源重组修复（HRR）缺陷的细胞/肿瘤（如携带BRCA1和/或BRCA2突变的细胞）。目前，Lynparza已在美国、欧盟、日本及许多其他国家和地区获批，用于治疗gBRCAm、HER2-高危早期乳腺癌等。一季度，Lynparza销售额为7.26亿美元，同比增长5%。Calquence（阿可替尼）作为一款鲁顿氏酪氨酸激酶（BTK）抑制剂，已获批用于多种血液瘤治疗。一季度，Calquence营收7.62亿美元，同比增长8%。BMSBMS一季度总营收为112亿美元，同比减少6%。肿瘤领域，Opdivo（纳武利尤单抗）和Opdualag（纳武利尤单抗+瑞拉利单抗）贡献了主要业绩。Opdivo是一款PD-1免疫检查点抑制剂，旨在解除肿瘤对人体自身免疫系统的抑制，帮助恢复抗肿瘤免疫反应。一季度，Opdivo总营收为22.65亿美元，同比增长9%。Opdualag首个获得批准的PD-1+LAG-3组合抗体疗法，2022年3月，FDA批准Opdualag用于治疗患有不可切除或转移性黑色素瘤的12岁及以上儿童和成人患者。通过靶向两种免疫检查点通路，Opdualag增强了T细胞活性，以提升抗肿瘤反应。一季度，Opdualag营收6.24亿美元，同比增长7%。BMS的全球第2款口服KRAS G12C抑制剂Krazati(adagrasib)，一季度收入4800万美元，同比增长125%。该药具有长达24小时的半衰期和广泛的组织分布，而且能够穿过血脑屏障，有助于最大限度地发挥药物效力。2022年底，Krazati获FDA加速批准上市，用于治疗携带KRAS G12C突变的经治NSCLC患者。值得一提的是，Krazati由Mirati Therapeutics研发，2023年10月，BMS以48亿美元收购Mirati，囊获此款疗法。BMS的传统化疗药物Abraxane（白蛋白紫杉醇），一季度营收为1.05亿美元，同比降低52%。肿瘤领域作为大病赛道，当中纷争或永不落幕，在这片充满挑战与机遇的战场上，制药巨头们激烈角逐，在你追我赶中，推动了整个肿瘤治疗领域的进步。主要参考资料：       1. 药企2025Q1财报       2. https://www.merck.com/news/welireg-belzutifan-receives-first-european-commission-approval-for-two-indications/.       3. https://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-recommended-for-eu-approval-for-ls-sclc.html.       4. https://www.businesswire.com/news/home/20250117223765/en.END【企业推荐】领取CPHI & PMEC China 2025展会门票来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

TOKYO, Japan & BASKING RIDGE, NJ, USA I May 07, 2025 I Positive topline results from the DESTINY-Breast11 phase 3 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 this analysis; however, EFS data showed an early positive trend favoring ENHERTU followed by THP compared to standard of care. The trial will continue to follow EFS. ENHERTU is a specifically engineered HER2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). 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. 3,4 The current standard of care in many regions of the world in this neoadjuvant setting consists of combination chemotherapy regimens. These regimens often include anthracyclines, which can be challenging for patients to tolerate and may result in long-term cardiovascular side effects. Further, nearly half of patients who receive neoadjuvant treatment do not achieve pCR, reinforcing the need for new treatment options. 2,5 “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,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “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.” “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,”said Susan Galbraith, MBBChir, PhD, Executive Vice President, Oncology Hematology R&D, AstraZeneca. “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.” 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 enrollment in a third arm of the study evaluating ENHERTU alone was closed based on a previous interim efficacy assessment of the study arms. Data from DESTINY-Breast11 will be presented at an upcoming medical meeting and shared with regulatory authorities. ENHERTU has demonstrated improved outcomes in six phase 3 breast cancer trials across different subtypes and stages of disease, including the recently announced DESTINY-Breast09 trial in the first-line HER2 positive metastatic setting. ENHERTU is also being studied in several ongoing breast cancer trials, including the DESTINY-Breast05 phase 3 trial, which is evaluating ENHERTU in the high-risk adjuvant early HER2 positive setting. About DESTINY-Breast11 DESTINY-Breast11 is a global, multicenter, randomized, open-label, phase 3 trial evaluating the efficacy and safety of neoadjuvant ENHERTU (5.4 mg/kg) monotherapy or ENHERTU followed by THP (paclitaxel, trastuzumab and pertuzumab) versus the standard of care regimen in patients with high-risk (lymph node positive [N1-3] or primary tumor stage T3-4), locally advanced or inflammatory HER2 positive early-stage breast cancer. Patients were randomized 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 rate of 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 . About HER2 Positive Early Breast Cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 6 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally. 6 HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers. 7 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. 8 Approximately one in five cases of breast cancer are considered HER2 positive. 9 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. 3,4 The current standard of care in many regions of the world in this neoadjuvant setting consists of combination chemotherapy regimens. These regimens often include anthracyclines, which can be challenging for patients to tolerate and may result in long-term cardiovascular side effects. Further, nearly half of patients who receive neoadjuvant treatment do not achieve pCR, reinforcing the need for new treatment options. 2,5 About ENHERTU ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) 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 program 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 (5.4 mg/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 hybridization (ISH)+) breast cancer who have received a 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 (5.4 mg/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 (5.4 mg/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 has progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial. ENHERTU (5.4 mg/kg) is approved in more than 50 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors 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 U.S. for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (6.4 mg/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 IHC 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 may be contingent upon verification and description of clinical benefit in a confirmatory trial. ENHERTU (5.4 mg/kg) is approved in Brazil, Israel, Russia, Saudi Arabia, Taiwan, U.K. and the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02 , DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. About the ENHERTU Clinical Development Program A comprehensive global clinical development program is underway evaluating the efficacy and safety of ENHERTU as a monotherapy or in combination or sequentially with other anti-cancer therapies across multiple HER2 targetable cancers. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019 and DATROWAY ® 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. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and DATROWAY, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Please see accompanying full Prescribing Information , including Boxed WARNINGS, and Medication Guide . About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com . SOURCE: Daiichi Sankyo