Ipilimumab

▎药明康德内容团队编辑 优先审评是中国国家药品监督管理局药品审评中心（CDE）推出的加速药物获批上市的重要政策之一。根据CDE发布的《2023年度药品审评报告》，获得优先审评审批的药物上市注册申请的审评时限由常规程序的200日缩短为130日，获批速度显著提升。 根据CDE官网公示信息，截至6月27日，2024年上半年共计有26个创新药的上市申请正式被纳入优先审评。从治疗领域来看，抗肿瘤药物最多，有17个，占比超65%。本文中就让我们来看看这些抗肿瘤药物都有哪些？它们都有望惠及哪些癌症患者？ 数据来源：CDE官网，《医药观澜》梳理。本表仅统计正式被纳入优先审评的药物，不含拟纳入药品。统计截至日期：2024年6月27日 辉瑞：elranatamab注射液 作用机制：BCMA×CD3双特异性抗体 适应症：多发性骨髓瘤 2024年1月，辉瑞（Pfizer）公司的elranatamab注射液上市申请被CDE纳入优先审评，用于治疗既往接受过至少三种治疗的复发或难治性多发性骨髓瘤（MM）成人患者。Elranatamab是一款皮下注射BCMA×CD3双特异性抗体，其一端与骨髓瘤细胞上的BCMA相结合，另一端与T细胞表面的CD3受体结合，使它们结合在一起并激活T细胞杀死骨髓瘤细胞。该药已于2023年获FDA加速批准，用于治疗复发/难治性MM患者。 正大天晴：TQB2450、安罗替尼 作用机制：抗PD-L1单抗、酪氨酸激酶抑制剂 适应症：子宫内膜癌 2024年1月，正大天晴申报的TQB2450注射液和安罗替尼胶囊联合疗法的一项上市申请被CDE纳入优先审评， 拟用于治疗既往接受过一、二线化疗方案治疗失败或不能耐受的非微卫星高度不稳定（非MSI-H）或非DNA错配修复缺陷（非dMMR）的复发性或转移性子宫内膜癌患者。贝莫苏拜单抗（TQB2450）是一款抗PD-L1人源化单克隆抗体，已于今年5月获批联合安罗替尼胶囊和依托泊苷及卡铂一线治疗广泛期小细胞肺癌。安罗替尼是一种新型小分子多靶点酪氨酸激酶抑制剂，此前已在中国获批用于治疗多种肿瘤适应症。 默沙东：belzutifan片 作用机制：HIF-2α抑制剂 适应症：血管母细胞瘤或胰腺神经内分泌肿瘤 2024年2月，默沙东（MSD）的belzutifan片上市申请被CDE纳入优先审评，拟用于治疗von Hippel-Lindau（VHL）病相关肾细胞癌、中枢神经系统血管母细胞瘤或胰腺神经内分泌肿瘤。VHL是一种罕见遗传疾病，它可异常激活癌症患者体内的缺氧诱导因子（HIF-2α）。Belzutifan是一款选择性新型口服HIF-2α抑制剂，此前已获FDA批准用于治疗VHL疾病相关癌症。 强生：塔奎妥单抗 作用机制：GPRC5D×CD3双抗 适应症：多发性骨髓瘤 2024年2月，强生（Johnson & Johnson）公司申报的塔奎妥单抗注射液被CDE纳入优先审评，单药治疗既往接受过至少三种治疗的复发或难治性多发性骨髓瘤成人患者。公开资料显示，塔奎妥单抗（talquetamab）是一款皮下注射双特异性抗体，靶向GPRC5D和CD3，已于2023年8月获美国FDA加速批准上市，用于治疗复发性或难治性多发性骨髓瘤成人患者。 图片来源：123RF 第一三共、阿斯利康：德曲妥珠单抗 作用机制：HER2靶向ADC 适应症：非小细胞肺癌 2024年2月，第一三共（Daiichi Sankyo）公司申报的注射用德曲妥珠单抗被CDE正式纳入优先审评，拟定适应症为：存在HER2（ERBB2）激活突变且既往接受过至少一种系统治疗的不可切除或转移性成人NSCLC患者。德曲妥珠单抗是阿斯利康（AstraZeneca）和第一三共联合开发的一款靶向HER2的抗体偶联药物（ADC），此前已在中国获批治疗HER2阳性和HER2低表达成人乳腺癌患者。 葆元医药/信达生物：泰莱替尼 作用机制：ROS1抑制剂 适应症：非小细胞肺癌 2024年2月，葆元医药（现已被Nuvation Bio收购）申报的泰莱替尼胶囊上市申请被CDE纳入优先审评，用于未经ROS1-TKI治疗的ROS1阳性局部晚期或转移性NSCLC成人患者的治疗。泰莱替尼是新一代口服选择性ROS1抑制剂，具有脑渗透潜力。2021年6月，葆元与信达生物签订了独家许可协议，在大中华区（包括中国大陆、香港、澳门和台湾地区）共同开发和商业化泰莱替尼。 信达生物、和黄医药：信迪利单抗、呋喹替尼 作用机制：PD-1抑制剂、VEGFR抑制剂 适应症：子宫内膜癌 2024年3月，信达生物的PD-1抑制剂信迪利单抗与和黄医药的VEGFR抑制剂呋喹替尼的联合疗法上市申请被CDE纳入优先审评，拟用于既往系统性抗肿瘤治疗后疾病进展且不适合进行根治性手术治疗或根治性放疗的晚期pMMR或non MSI-H子宫内膜癌患者。公开资料显示，信达生物与和黄医药曾在2018年达成合作，开展信迪利单抗与呋喹替尼用于实体瘤联合治疗的研究。 复星医药：FCN-159 作用机制：MEK1/2抑制剂 适应症：树突状细胞和组织细胞肿瘤、神经纤维瘤 2024年4月，复星医药的FCN-159片（复迈替尼）上市申请被CDE纳入优先审评，拟用于治疗成人树突状细胞和组织细胞肿瘤。2024年5月，FCN-159片的新适应症上市申请再次被CDE纳入优先审评，用于治疗2岁及2岁以上儿童1型神经纤维瘤病（NF1）相关的丛状神经纤维瘤。FCN-159为一款MEK1/2选择性抑制剂，可以抑制RAS通路异常引起的肿瘤增殖，拟开发主要用于治疗晚期实体瘤、I型神经纤维瘤、树突状细胞和组织细胞肿瘤、低级别脑胶质瘤等适应症。 图片来源：123RF 百时美施贵宝：伊匹木单抗、纳武利尤单抗 作用机制：CTLA-4抗体、PD-1抑制剂 适应症：MSI-H/dMMR结直肠癌 2024年3月和4月，伊匹木单抗注射液和纳武利尤单抗注射液的联合疗法上市申请先后两次被CDE纳入优先审评，针对的适应症均为两种药物联合用于一线治疗不可切除或转移性微卫星高度不稳定性（MSI-H）或错配修复缺陷型（dMMR）结直肠癌患者。伊匹木单抗是一款CTLA-4抗体，纳武利尤单抗是一款PD-1抑制剂。今年3月，伊匹木单抗联合纳武利尤单抗一线治疗MSI-H/dMMR结直肠癌的申请已被CDE纳入突破性治疗药物品种。 恒瑞医药：阿帕替尼、氟唑帕利 作用机制：VEGFR2靶向药物、PARP抑制剂 适应症：HER2阴性乳腺癌 2024年4月，恒瑞医药的甲磺酸阿帕替尼片和氟唑帕利胶囊各有一项新适应症上市申请被CDE纳入优先审评。其中，阿帕替尼是一款VEGFR2靶向药物，本次申报上市的适应症是联合氟唑帕利用于治疗伴有胚系BRCA突变（gBRCAm）的HER2-乳腺癌患者。氟唑帕利是一款PARP抑制剂，本次申报上市的适应症是单药或联合阿帕替尼用于治疗伴有胚系BRCA突变的HER2-乳腺癌患者。 罗氏：GDC-0077 作用机制：PI3Kα抑制剂 适应症：乳腺癌 2024年4月，罗氏（Roche）GDC-0077（inavolisib）的上市申请被CDE纳入优先审评，拟与CDK4/6抑制剂哌柏西利和内分泌疗法联合用药，用于治疗PIK3CA突变、HR阳性/HER2阴性的局部晚期或转移性乳腺癌成人患者。公开资料显示，PIK3CA基因突变在大约40%的HR阳性乳腺癌中被发现，GDC-0077是一种具有双重作用机制的口服疗法，具有高度的体外PI3Kα抑制效力和选择性，且能够特异性触发PI3Kα蛋白突变体的分解。 图片来源：123RF 加科思：格来雷塞 作用机制：KRAS抑制剂 适应症：非小细胞肺癌（NSCLC） 2024年5月，加科思格来雷塞片（JAB-21822片）的上市申请被CDE纳入优先审评，拟用于既往接受过至少一线系统性治疗的KRAS G12C突变的局部晚期或转移性NSCLC成人患者的治疗。格来雷塞是一款KRAS G12C抑制剂，本次上市申请是基于在中国开展的2期注册性临床研究结果。数据显示，格来雷塞单药治疗KRAS  G12C突变NSCLC患者，确认的客观缓解率（ORR）为47.9%，疾病控制率（DCR）为86.3%，中位无进展生存期（mPFS）为8.2个月，中位总生存期（mOS）为13.6个月。 诺诚健华：坦昔妥单抗 作用机制：抗CD19单抗 适应症：弥漫性大B细胞淋巴瘤（DLBCL） 2024年6月，诺诚健华注射用坦昔妥单抗的上市申请被CDE纳入优先审评，拟联合来那度胺用于治疗复发或难治性且不适合自体干细胞移植的DLBCL成人患者。坦昔妥单抗是诺诚健华从Incyte公司引进的一款靶向CD19的Fc结构域优化的人源化单克隆抗体，此前已获得美国FDA以和欧洲药品管理局（EMA）批准上市，联合来那度胺治疗不适合自体干细胞移植条件的复发/难治性DLBCL患者。 除了上述正式被纳入优先审评的抗肿瘤药物，近日还有三款抗肿瘤新药被CDE纳入了拟优先审评公示名单，分别为： 和黄医药递交的EZH2甲基转移酶抑制剂他泽司他，拟用于治疗EZH2突变阳性且既往接受过至少两种系统性治疗的复发或难治性滤泡性淋巴瘤成人患者； 阿斯利康的第三代EGFR-TKI奥希替尼的新适应症上市申请，拟用于接受含铂放化疗期间或之后未出现疾病进展、具有EGFR外显子19缺失或外显子21（L858R）置换突变的局部晚期、不可切除（III期）NSCLC成人患者的治疗； 精准生物的pCAR-19B细胞自体回输制剂（普基仑赛注射液），拟用于治疗3～21岁CD19阳性的复发或难治性B细胞急性淋巴细胞白血病患者。 希望这些抗肿瘤新药能够早日获批，为广大癌症患者带来新的治疗选择。 优先审评之外，2024年上半年，中国创新药领域还迎来了许多其它方面的进展。为方便读者了解今年上半年中国创新药行业的整体动态，《医药观澜》特地制作了《2024年上半年中国创新药领域亮点概览》白皮书，供读者参阅。内容包含： 2024上半年NMPA批准上市的新药数据分析 2024上半年NMPA纳入优先审评的新药分析 2024上半年NMPA纳入突破性治疗品种的新药分析 2024上半年在中国获批IND的1类新药分析 2024上半年中国公司就创新药达成的授权合作数据分析 2024上半年中国创新药投融资数据分析 2024上半年获FDA快速通道资格的中国新药分析 2024上半年获FDA孤儿药资格的中国新药分析 如欲了解上半年更多中国创新药领域的进展，请扫描下方二维码，您将可以获取由我们整理的《2024年上半年中国创新药发展白皮书》（限时下载）。 参考资料： [1]中国国家药监局药品审评中心（CDE）官网. Retrieved June 27，2024, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [2] 各公司官方资料及公开新闻稿。 本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

City of Hope developed a novel use of biotherapeutic product CBM588 in the treatment of cancer; new research suggests the agent adjusts people’s microbiome, possibly leading to enhanced effectiveness of Food and Drug Administration-approved cancer immunotherapies Scientists are in discussions to translate City of Hope’s promising phase 1 trial results into a global phase 2/3 trial sponsored by the SWOG Cancer Research Network LOS ANGELES--(BUSINESS WIRE)-- Physician scientists from City of Hope, one of the largest cancer research and treatment organizations in the United States, found that people with metastatic kidney cancer who orally took a live biotherapeutic product called CBM588 while in treatment with immunotherapy and enzymatic tyrosine kinase inhibitors experienced improved health outcomes. The phase 1 trial was published today in Nature Medicine. Microorganisms in the gut modulate the immune system. City of Hope researchers are now in discussions with the global SWOG Cancer Research Network to design a phase 2/3 trial to assess the City of Hope-identified novel use of CBM588 and microbiome modulation in people with advanced cancer. Sumanta Pal, M.D., professor and vice chair of academic affairs in City of Hope’s Department of Medical Oncology & Therapeutics Research, is slated to be co-leader of the potential phase 2/3 SWOG trial. “We at City of Hope are the first to demonstrate a live bacterial product’s ability to improve clinical outcomes for patients with kidney cancer treated with immunotherapy. CBM588 could be exciting in cancer treatment because of its potential to enhance the efficacy of immune checkpoint inhibitor-based treatment, improve patient outcomes and modulate the gut microbiota in beneficial ways,” said Pal, a City of Hope medical oncologist and corresponding author of the new study. “Ongoing and larger clinical trials are crucial to validate these benefits and address current challenges. If the positive results observed in this small trial and a previous trial with nivolumab and ipilimumab are confirmed, CBM588 could become a valuable supplement in the treatment of various cancers, particularly for patients treated with immune checkpoint inhibitors." An estimated 44% of U.S. patients with cancer in 2018 were eligible for checkpoint inhibitor drugs, according to a JAMA Network Open article that flags the increasing trend of this percentage. In the single-center, phase 1 trial, 30 people with metastatic kidney cancer were randomized to receive cabozantinib, an inhibitor of vascular endothelial growth factor receptor, and targeted immunotherapy nivolumab with or without CBM588 as first-line treatment. Participants’ gut microbiome were analyzed via stool samples in the beginning for a baseline and then 13 weeks into treatment. City of Hope has granted an exclusive worldwide license to Osel for intellectual property on the novel use of CBM588 to enhance the efficacy of checkpoint inhibitors used to treat cancer, including metastatic renal cell carcinoma. Scientists from Osel and Miyarisan Pharmaceutical Co. Ltd, the manufacturer of CBM588, collaborated on the study. To date, many studies on lung cancer, melanoma and metastatic kidney cancer, among other diseases, have shown that the composition of the gut microbiome could predict immunotherapy outcomes for patients with cancer. Current guidelines for metastatic renal cell carcinoma (kidney cancer) recommend that newly diagnosed patients receive either dual checkpoint inhibitor therapy or a combination of immunotherapy and tyrosine kinase inhibitor, but most patients eventually experience disease progression while on treatment. Positive patient outcomes usually do not last, and subsequent treatments are largely palliative rather than curative. So, physician scientists are looking to combine current strategies with new treatments that do not introduce toxic side effects, such as through microbiome modulation. In the trial, City of Hope researchers observed an increase in the abundance of unclassified Ruminococcaceae genera, which has been linked with improved clinical outcomes with immune checkpoint inhibitors in recent studies. Clostridium butyricum MIYAIRI 588, the bacterium in CBM588, produces butyric acid, which is critical for intestinal health and is a well-known immunomodulator. “While not yet part of standard cancer treatment protocols, microbiome modulation is a promising area of research with the potential to enhance the efficacy of cancer therapies, particularly immunotherapies. Current applications are primarily within clinical trials, but the growing body of evidence suggests that microbiome-based interventions may soon become a valuable component of cancer treatment strategies,” said Hedyeh Ebrahimi, M.D, M.P.H., City of Hope postdoctoral medical oncology fellow and first author of the study. City of Hope is accelerating its research on the direct link between a healthy gut and the effectiveness of immune therapies, such as CAR T cell therapy. Its enhanced microbiome program spans from basic to clinical research and includes studying the gut microbiome’s role in protecting transplant patients from complications experienced during their recovery. “This study demonstrates again that the microbiome has an important role in the efficacy and toxicity of cancer immunotherapy and can be targeted to improve outcome,” said Marcel van den Brink, M.D., Ph.D., president of City of Hope Los Angeles and City of Hope National Medical Center, and the Deana and Steve Campbell Chief Physician Executive Distinguished Chair. The Nature Medicine study entitled “Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial” was supported by Exelixis Inc. (XL184-IST123). CBM588 was supplied by Miyarisan Pharmaceutical Co., Ltd. and Osel Inc. About City of Hope City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn. View source version on businesswire.com: Contacts Zen Logsdon 626-409-9367 zlogsdon@coh.org Source: City of Hope View this news release online at: