Savolitinib

LONDON, UK I June 25, 2024 I High-level results from the ADJUVANT BR.31 Phase III trial, sponsored by the Canadian Cancer Trials Group (CCTG), showed Imfinzi (durvalumab) did not achieve statistical significance for the primary endpoint of disease-free survival (DFS) versus placebo in early-stage (IB-IIIA) non-small cell lung cancer (NSCLC) after complete tumour resection in patients whose tumours express PD-L1 on 25% or more tumour cells. ​Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “We are disappointed in the ADJUVANT BR.31 results. Imfinzi has helped change the treatment landscape and achieved multiple positive Phase III trials for patients with earlier stages of lung cancer. We are committed to addressing the remaining unmet need in lung cancer through our broad development programme.” The safety profile for Imfinzi was consistent with its known safety profile, and no new safety concerns were reported. The data will be shared at a forthcoming medical meeting. Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiotherapy based on the PACIFIC Phase III trial. Imfinzi is also being investigated as monotherapy and in combinations in several other early-stage lung cancer settings, including in medically inoperable or unresected Stage I-II NSCLC (PACIFIC-4) and unresectable, Stage III NSCLC (PACIFIC-5, 8 and 9). Notes Lung cancer Each year, there are an estimated 2.4 million people diagnosed with lung cancer globally. Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths. 1-2 Lung cancer is broadly split into NSCLC and small cell lung cancer (SCLC), with 80-85% of patients diagnosed with NSCLC. 3-4 The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis. 5-6 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition. 7-8 The majority of patients with resectable disease eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy. 9 Only around 58% of patients with Stage IB disease will survive for five years. This decreases to 36-46% for patients with Stage II and 24% for patients with Stage IIIA disease, reflecting a high unmet medical need. 10 ADJUVANT BR.31 ADJUVANT BR.31 is a randomised, multi-centre, double-blind Phase III trial sponsored by CCTG evaluating Imfinzi in the adjuvant treatment of 1,415 patients with Stage IB (≥4cm), II or IIIA (Seventh Edition AJCC Cancer Staging Manual) NSCLC following complete tumour resection with or without adjuvant chemotherapy. AstraZeneca provided Imfinzi and support for the trial. Patients were randomised 2:1 to receive a 20mg/kgIV infusion of Imfinzi or placebo every four weeks for up to 48 weeks. The trial is being conducted at 269 centres across 19 countries and regions including in Canada, the US, Australia, Europe and Asia. The primary endpoint is DFS in patients whose tumours express PD-L1 on 25% or more tumour cells and do not have known common EGFR mutations or ALK rearrangements. Key secondary endpoints include DFS in patients whose tumours express PD-L1 on 1% or more of cells and in patients regardless of PD-L1 tumour cell expression status, overall survival and safety. DFS is defined as time from randomisation to date of first recurrence, new cancer or death from any cause and is recognised as an important clinical measure by both physicians and patients. Canadian Cancer Trials Group (CCTG) CCTG is an academic cancer clinical trials research cooperative that runs Phase I-III trials to test anti-cancer and supportive therapies at over 85 hospitals and cancer centres across Canada. From the operations centre at Queen’s University, CCTG has supported more than 600 trials enrolling 100,000 patients from 40 countries on 6 continents through a global network of 20,000 investigators and clinical trial staff. CCTG is a national program of the Canadian Cancer Society, and their aim is to improve survival and quality of life for all people with cancer. Imfinz i Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses. Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiation therapy. Imfinzi is also approved for the treatment of extensive-stage SCLC and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC. Imfinzi also demonstrated statistically significant and clinically meaningful event-free survival results in patients with resectable early-stage NSCLC based on the AEGEAN Phase III trial. Imfinzi in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery is approved for patients in Switzerland based on this trial. In limited-stage SCLC, Imfinzi demonstrated statistically significant and clinically meaningful improvements in the dual primary endpoints of OS and progression-free survival (PFS) compared to placebo in patients who had not progressed following standard-of-care concurrent chemoradiotherapy in the ADRIATIC Phase III trial. In addition to its indications in lung cancers, Imfinzi is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU and in combination with chemotherapy (carboplatin plus paclitaxel) followed by Imfinzi monotherapy in primary advanced or recurrent endometrial cancer that is mismatch repair deficient in the US. Since the first approval in May 2017, more than 220,000 patients have been treated with Imfinzi . As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, breast cancer, several gastrointestinal and gynaecologic cancers, and other solid tumours. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi and Imjudo ; Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. AstraZeneca in immuno-oncology (IO) AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours. AstraZeneca strives to redefine cancer care and help transform outcomes for patients with Imfinzi as a monotherapy and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T cell engagers. AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure. 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 . References 1. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf . Accessed June 2024. 2. World Health Organization. International Agency for Research on Cancer. World Fact Sheet. Available at: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/populations/900-world-fact-sheet.pdf . Accessed June 2024. 3. LUNGevity Foundation. Types of Lung Cancer. Available at: https://www.lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer . Accessed June 2024. 4. Cheema PK, et al. Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer. Curr Oncol . 2019;26(1):37-42. 5. Cagle PT, et al . Lung Cancer Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med. 2013;137(9):1191-1198. 6. Le Chevalier T. Adjuvant Chemotherapy for Resectable Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol. 2010;21(suppl 7):vii196-198. 7. Sethi S, et al. Incidental Nodule Management – Should There Be a Formal Process? J Thorac Dis . 2016:8(Suppl 6);S494-S497. 8. LUNGevity Foundation. Screening and Early Detection. Available at: https://www.lungevity.org/lung-cancer-basics/screening-early-detection . Accessed June 2024. 9. Pignon JP, et al . Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552-3559. 10. Goldstraw P, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol . 2007;2(8):706-14. SOURCE: AstraZeneca

从抗击各种疾病的新药问世，到对罕见病治疗方法的不断探索，药品研发不仅为人类的健康带来了福音，也极大地丰富了生命科学的研究领域。全球范围内，药品研发的热度不断升温，而中国作为世界第二大经济体，在药品研发领域也展现出强大的实力和潜力，一份专注于药物研发分析的《全球及中国药品研发热度地图》（下文简称《药品研发地图》）应运而生。 本文将基于《药品研发地图》及米内网全球药物研发库的统计数据，聚焦全球及中国药品研发的最新动态和趋势，帮助读者深入了解药品研发的热点领域、关键技术、重要企业......更多精彩内容和核心数据将在2024米思会上以展板形式呈现，干货满满，敬请期待！ 新药研发TOP20“大比拼”，企业、适应症、靶点...... 米内网全球药物研发数据库显示，新药TOP20适应症方面，全球竞争格局中以炎症性疾病、疼痛、阿尔茨海默病、乳腺癌等疾病为主，其相关药物均超过2000个（统计范围自药物发现阶段至已上市阶段，下同）。目前已上市品种数最多的适应症为非胰岛素依赖型糖尿病，有164个；提交上市申请品种数最多的适应症为疼痛，有32个。 而国内竞争格局中，转移性非小细胞肺癌、非胰岛素依赖型糖尿病、非小细胞肺癌、乳腺癌、转移性乳腺癌等位居前五，相关药物均超过300个。目前已上市品种数最多的适应症为非胰岛素依赖型糖尿病和乙型肝炎病毒感染，均有62个；提交上市申请品种数超过10个的适应症有4个，包括转移性非小细胞肺癌、非胰岛素依赖型糖尿病、转移性乳腺癌以及类风湿性关节炎。 全球新药TOP20适应症/品种格局（单位：个） 中国新药TOP20适应症/品种格局（单位：个） 新药TOP20企业方面，在全球竞争格局中，辉瑞、GSK、默沙东、赛诺菲、罗氏等外资厂商遥遥领先，涉及相关药物的数量（含重复计算）均在1000个及以上；而在国内竞争格局中，恒瑞医药、正大制药、国药集团、复星医药和石药集团力压一众外资药企，问鼎榜单前五名，此外，挺进榜单TOP20的国内药企还有先声药业、信达生物、上海医药和百济神州等。 全球新药TOP20企业/项目格局（单位：个） 中国新药TOP20企业/项目格局（单位：个） 新药TOP20靶点格局中，EGFR和HER2是“热门选手”，在全球和中国范围内，涉及的相关药物数量均高居第一位和第二位。此外，PD-L1、CD19、PD-1、GLP-1、CD3、TNF等热门靶点均凭借过百个相关药物踏入榜单前十之列。 阿兹海默症、疼痛、NASH......全球热点适应症“全剖析” 有效选择少、市场潜力大、关注度高等关键指标，是划分全球热点适应症的重要参考依据。对此，米内网将根据上述三大指标，挑选出部分业内高度关注的适应症进行多维度透视和全方位剖析。 比如，阿兹海默症目前有超过2000款药物在研，其中超过1600款药物处于临床前或药物发现阶段，已获批上市的药物约有37款，但疗效大多不太理想。作为“新晋”明星产品，卫材的仑卡奈单抗于2023年1月获FDA咨询委员会全票支持通过、批准上市，并于2023年9月、2024年1月先后登陆日本和中国市场。 阿兹海默症各研发阶段品种格局（单位：个） 疼痛目前有超过2000款药物在研，其中有156款药物获批上市，已提交上市申请的药物有32款，处于Ⅲ期临床的药物有98款。从TOP20靶点上看，OPRM1、OPR、COX、COX2涉及相关药物均超过100个，已上市的药品分别达50个、21个、37个和20个，其合计上市药品数占疼痛适应症已上市药品总数的八成以上。 疼痛TOP20靶点/品种格局（单位：个） 代谢相关脂肪性肝炎(NASH)目前以临床前及药物发现的药物居多，合计超过400款，而已上市的药物及已提交上市申请的药物仅有2款和1款。TOP20企业方面，阿斯利康、勃林格殷格翰、诺华、辉瑞等外资厂商涉及在研药物较多，而众生药业、无锡药明康德药业、上海拓臻生物科技、先为达生物等国内药企也纷纷迈进TOP20之列。 NASH适应症TOP20企业/项目格局（单位：个） 此外，结直肠肿瘤（不含转移性结直肠肿瘤）、年龄相关性黄斑变性、衰老等热门适应症，已获批上市的药物均少于20款，而处于研发阶段的药物均超过百款；从TOP20地区分布情况看，美国、中国、英国、日本、韩国、德国等为在研药物较多、较集中的地区。 “新”、“快”、“缺”等中国“特色”药物靶点“全透视” “中国新”靶点，指的是全球已上市，中国暂未上市，但已有在研发的靶点。据米内网统计，目前国内共有270多个“中国新”靶点，其中处于Ⅲ期临床的“中国新”靶点最多，有74个，占比约为27%。 “中国新”靶点最高研发阶段格局 在“中国新”靶点中，CLDN18.2是最为突出的靶点之一，目前国内该类靶点在研药物有75个，是“中国新”靶点中涉及在研药物最多的靶点。安斯泰来制药的佐妥昔单抗是目前全球唯一获批上市的CLDN18.2靶向药，在国内正处于申报上市在审阶段。 “中国快”靶点指的是：全球未有上市，国内有处于临床研发阶段及以上的靶点，且该靶点在国内药物最高研发阶段全球最先。据米内网统计，国内该类靶点合计223个，其中处于Ⅱ期临床的数量最多，占比达44%。 此外，处于提交上市申请阶段的“中国快”靶点有8个，包括：GNEF、ITGA5/B3、ITGA2B/B3、NRG1、ACAT、Oxyntomodulin ligand、PTEN、Ubiquitin ligase。其中，巴替非班由百奥泰研发，是一款靶向ITGA5/B3的1类新药，用于不稳定型心绞痛或非Q波心肌梗塞治疗，目前在国内处于报产在审阶段，上市可期。 巴替非班全球研发进度 “中国缺”靶点是指：全球已有研发上市，但中国未有企业布局的靶点。米内网数据显示，目前共有3000余个“中国缺”靶点，其中处于临床前或其更早阶段的合计占比超过五成，处于临床及以上阶段的约有1321个。 值得一提的是，“中国缺”靶点在全球已有布局，是创新药物的摇篮。该类靶点在中国的空窗期可能是创新药企实现“快人一步”的关键时期，研究价值大。 “中国缺”靶点TOP20分布（单位：个） 国产1类新药获批靶点解析，PD-(L)1、EGFR......成热门选手 2023年是国产创新药收获颇丰的一年。伴随兆科药业的索卡佐利单抗、恒瑞医药的阿得贝利单抗、正大天晴药业的派安普利单抗、信达生物的托莱西单抗等1类新药获批上市，PD-1/PD-L1、EGFR、c-Met、ATP4A、PCSK9等相关靶点的表现亦十分亮眼。 米内网数据显示，上述热门靶点目前均涉及不少在研药物，其中，EGFR在全球的在研药物最多，有729个；PD-1/PD-L1在国内在研药物最多，有315个。 部分热门靶点在全球及中国的在研药物数量（单位：个） PD-1/PD-L1为最热门的靶点之一，2023年在国内有3款1类新药获批上市，包括索卡佐利单抗、阿得贝利单抗和派安普利单抗。截至目前，全球已有17款PD-1药物和8款PD-L1药物获批，其中在中国上市的分别有11款和6款。 值得关注的是，目前中国在研的PD-1/PD-L1药物合计超过300个，靶点研发拥挤程度高，其中超过半数的药物仍处于临床前或药物发现阶段，入局的企业需谨慎。 中国在研PD-1/PD-L1药物情况 EGFR是一种跨膜酪氨酸激酶受体，它可促进许多细胞的生长和分化，包括胚胎发育、成年组织的维持和修复、以及癌症细胞的增殖和转移，疗效优势十分突出。 与此同时，EGFR也是一个相当热门的靶点，全球已有36个该靶点相关药物获批上市；在中国开展研究的药物超过200个，其中已上市的有24个（约占9%），提交上市申请的有10个（约占4%），处于Ⅲ期临床的有18个（约占7%），处于Ⅱ期临床的有35个（约占14%），处于Ⅰ期临床的有42个（约占16%）。 全球在研EGFR药物分布（单位：个） c-Met又名肝细胞生长因子受体(HGFR)，能促进细胞增殖、细胞生长、血管生成等。目前，全球已获批上市的c-Met药物有9个，其中4个已在中国获批，分别为克唑替尼、赛沃替尼、伯瑞替尼和谷美替尼。在研c-Met药物中，处于临床前或药物发现早期阶段的占比合计超过五成，提交上市申请的有4个（约占5%），处于Ⅲ期临床的有5个（约占6%）。 ATP4A是一种细胞膜转运蛋白，也是消化系统的一个重要靶点。2023年在国内获批上市的ATP4A靶向1类新药包括安奈拉唑钠肠溶片、盐酸凯普拉生片等，适应症为十二指肠溃疡和反流性食管炎。米内网数据显示，ATP4A靶点在全球有140余个药物处于研发阶段，39个药物已获批上市；在中国有35个开展研究的药物，其中13个已获批上市，4个已提交上市申请在审。 PCSK9是一种由肝脏合成分泌的丝氨酸蛋白酶，可与低密度脂蛋白受体(LDLR)结合，促进细胞内降解以防止其再循环。目前已有4个PCSK9靶向药获批上市，包括安进的依洛尤单抗、赛诺菲的阿利西尤单抗、诺华的英克司兰、信达生物的托莱西单抗；在研新品方面，康方生物的伊努西单抗、君实生物的昂戈瑞西单抗、恒瑞医药的瑞卡西单抗等1类新药均处于申报上市阶段。 结语 通过《全球及中国药品研发热度地图》，米内网希望能为读者提供一个更全面、更深入的药品研发视角。让我们共同期待，在不久的未来，更多颇具临床价值、差异化的创新药面世，为人类的健康事业做出更大的贡献！ 数据来源：CDE官网、米内网数据库等注：数据统计截至2024年4月底 本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092 【分享、点赞、在看】点一点不失联哦