Trastuzumab biosimilar(Shanghai Henlius Biotech, Inc.)

2025年5月16日，复宏汉霖（2696.HK）宣布，公司自主研制的伊匹木单抗生物类似药HLX13（重组抗CTLA-4全人单克隆抗体注射液）的I/III期临床研究（NCT06841185）在中国完成首例受试者给药。复宏汉霖已于2025年4月与Sandoz达成授权许可合作，授予Sandoz对HLX13在美国、欧洲42个国家和地区、日本、加拿大及澳大利亚的独家商业化权益。近年来，免疫疗法为肿瘤治疗提供了新的途径，具有独特的优势和巨大的潜力。肿瘤免疫检查点抑制剂是肿瘤免疫治疗中的重要组成部分[1]。与PD-1/L1、LAG-3相似，细胞毒性T淋巴细胞相关抗原4（cytotoxic T-lymphocyte-associated protein 4, CTLA-4）也是一类免疫抑制型检查点蛋白，主要表达在调节性T细胞和活化的T细胞上。与CD28相比，CTLA-4对B7分子的亲和力更强，通过与CD28竞争性结合抗原呈递细胞上的B7配体（B7-1和B7-2），抑制T细胞的增殖和活化[2]。全人抗CTLA-4单克隆抗体能够解除CTLA-4对T细胞活化所需的共刺激信号的抑制，增加活性效应T细胞的数量，从而动员 T 细胞对肿瘤细胞发动直接免疫攻击。此外，抗CTLA-4单抗可选择性地耗尽肿瘤部位的调节T细胞，导致肿瘤内效应T细胞/调节T细胞的比例增加，从而导致肿瘤细胞死亡。研究证明，伊匹木单抗注射液与PD-1抑制剂组成的双免疫联合疗法能够产生协同的抗肿瘤效果，为患者带来更大的临床获益[3-4]。截至目前，伊匹木单抗联合纳武利尤单抗已在全球多个国家和地区获批，适应症包括联合纳武利尤单抗用于黑色素瘤、肝细胞癌等一系列适应症。HLX13（抗CTLA-4单抗）药理作用示意图HLX13是复宏汉霖严格按照中国、欧盟和美国等生物类似药法规自主研发的伊匹木单抗注射液生物类似药，有望用于多种实体瘤的治疗。公司已经完成了HLX13与原研药伊匹木单抗注射液的药学、临床前药理学、毒理学和药代动力学全面对比研究，上述临床前研究未发现HLX13与原研药伊匹木单抗注射液存在显著差异。未来，复宏汉霖还将持续立足于未满足的临床需求，充分发挥公司在抗体药物和抗体偶联药物领域的一体化平台优势，持续探索免疫治疗在肿瘤中的治疗潜力，为全球患者带来更多高质量、可负担的创新治疗方案。关于NCT06841185本研究为一项多中心、随机、双盲、平行对照1/3期临床研究，旨在评估HLX13与其原研药YERVOY®（美国市售和欧盟市售）在既往未经治疗的不可切除的晚期肝细胞癌（HCC）患者中的药代动力学（PK）特征、有效性、安全性和免疫原性相似性。合格的受试者将按2:1:1的比例随机分配至三组，在前4个周期，受试者每3周接受一次HLX13、美国市售的YERVOY®或欧盟市售的YERVOY®治疗，三组均联合纳武利尤单抗。随后每4周接受一次纳武利尤单抗治疗，最多10个周期。主要PK终点为从给药前至首次给药后21天的血药浓度-时间曲线下面积（AUC0-21d）和稳态给药间隔内血药浓度-时间曲线下面积（AUCss）；主要有效性终点为由独立放射学审查委员会（IRRC）根据实体肿瘤临床疗效评价标准（RECIST v1.1）评估的直至第24周的最佳客观缓解率（ORR）。次要终点包括其他PK参数、其他有效性评估、安全性及免疫原性。关于复宏汉霖复宏汉霖（2696.HK）是一家国际化的创新生物制药公司，致力于为全球患者提供可负担的高品质生物药，产品覆盖肿瘤、自身免疫疾病、眼科疾病等领域，已有6款产品在中国获批上市，4款产品在国际获批上市，5个上市申请分别获中国药监局、美国FDA和欧盟EMA受理。自2010年成立以来，复宏汉霖已建成一体化生物制药平台，高效及创新的自主核心能力贯穿研发、生产及商业运营全产业链。公司已建立完善高效的全球创新中心，按照国际药品生产质量管理规范（GMP）标准进行生产和质量管控，不断夯实一体化综合生产平台，其中，公司商业化生产基地已相继获得中国、欧盟和美国GMP认证。复宏汉霖前瞻性布局了一个多元化、高质量的产品管线，涵盖约50个分子，并全面推进基于自有抗PD-1单抗H药汉斯状®的肿瘤免疫联合疗法。截至目前，公司已获批上市产品包括国内首个生物类似药汉利康®（利妥昔单抗）、自主研发的中美欧三地获批单抗生物类似药汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™，欧洲商品名：Zercepac®）、汉达远®（阿达木单抗）、汉贝泰®（贝伐珠单抗）、全球首个获批一线治疗小细胞肺癌的抗PD-1单抗汉斯状®（斯鲁利单抗，欧洲商品名：Hetronifly®）以及汉奈佳®（奈拉替尼）。公司亦同步就19个产品在全球范围内开展30多项临床试验，对外授权全面覆盖欧美主流生物药市场和众多新兴市场。First Subject Dosed for Phase 1/3 Clinical Trial of Henlius’ Proposed Ipilimumab BiosimilarShanghai, China, May 16, 2025 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first subject was dosed for a phase 1/3 clinical trial of the company's independently developed ipilimumab biosimilar HLX13 (recombinant anti-CTLA-4 fully human monoclonal antibody injection) in China. In April 2025, Henlius entered into a license agreement with Sandoz, granting Sandoz the exclusive commercial rights for HLX13 in the United States, 42 European countries and regions, Japan, Canada, and Australia.Immune checkpoint inhibitors are playing a crucial part in immunotherapy, which has emerged in recent years as a novel approach to combating tumour cells with distinct advantages and enormous promise [1]. In addition to PD-1/L1 and LAG-3, CTLA-4 is also an inhibitory immune checkpoint which expressed on regulatory T cells and activated T cells and has a higher affinity to B7 molecules compared with CD28, thus can competitively bind to B7 molecules to inhibit the proliferation and activation of T cells [2]. Anti-CTLA-4 fully human monoclonal antibody (mAb) can block the inhibitory effects of CTLA-4 on the co-stimulation signal necessary to T cell activation and can increase the number of reactive T-effector cells which mobilize to mount a direct T-cell immune attack against tumour cells. Also, anti-CTLA-4 mAb may selectively deplete T-regulatory cells at the tumour site, leading to an increase in the intratumoral T-effector/T-regulatory cell ratio which drives tumour cell death. Meanwhile, results showed that the combination therapy of anti-CTLA-4 mAb and anti-PD-1 mAb is expected to have a synergistic effect and may bring additional clinical benefit to patients [3-4]. Currently, ipilimumab has been approved in various countries and regions in combination with nivolumab for the treatment of melanoma and hepatocellular carcinoma, among other indications.HLX13 is a biosimilar of ipilimumab independently developed by Henlius in accordance with the NMPA, EMA, FDA and other international biosimilar guidelines. The indications to be developed for HLX13 are solid tumours. Henlius has conducted a series of head-to-head pre-clinical studies to compare the chemical manufacture and control (CMC), pharmacology, toxicity, and pharmacokinetics profiles of HLX13 and originator ipilimumab. Results from these studies showed that there is a high similarity or no significant difference between HLX13 and originator ipilimumab.Looking forward, Henlius will continue to focus on unmet clinical needs and bring more high-quality, affordable and innovative therapeutic solutions to patients around the world by giving full play to the company's integrated platform advantages in the field of antibody drugs and antibody-drug conjugates, and by continuing to explore the therapeutic potential of immunotherapy in oncology field.About NCT06841185This study is a multicentre, randomized, double-blind, parallel-controlled Phase 1/3 clinical study to evaluate the similarity of pharmacokinetic (PK) profiles, efficacy, safety, and immunogenicity among HLX13 and its reference product YERVOY® (US-sourced and EU-sourced) as treatment for patients with unresectable advanced hepatocellular carcinoma (HCC) who have not received prior systemic therapy. Eligible subjects will be randomized in a 2:1:1 ratio to receive HLX13, US-sourced YERVOY® or EU-sourced YERVOY®. During the initial 4 treatment cycles, subjects across all study groups received the investigational product every 3 weeks in combination with nivolumab. Thereafter, nivolumab is administered every 4 weeks for up to 10 cycles. The primary PK endpoints are the area under the serum concentration-time curve from time 0 to 21 days (AUC0-21d) and the area under the serum concentration-time curve within a dosing interval at steady state (AUCss). The primary efficacy endpoint is the best objective response rate (ORR) assessed by the Independent Radiology Review Committee (IRRC) as per Response Evaluation Criteria In Solid Tumours version 1.1 (RECIST v1.1) up to Week 24. Secondary endpoints include other PK parameters, other efficacy assessments, safety, and immunogenicity.About HenliusHenlius (2696.HK) is a global biopharmaceutical company with the vision to offer high-quality, affordable and innovative biologic medicines for patients worldwide with a focus on oncology, autoimmune diseases and ophthalmic diseases. Up to date, 6 products have been launched in China, 4 have been approved for marketing in overseas markets, and 5 marketing applications have been accepted for review in China, the U.S. and the EU, respectively. Since its inception in 2010, Henlius has built an integrated biopharmaceutical platform with core capabilities of high-efficiency and innovation embedded throughout the whole product life cycle including R&D, manufacturing and commercialization. It has established global innovation centre and Shanghai-based commercial manufacturing facilities certificated by China, the EU and U.S. GMP.Henlius has pro-actively built a diversified and high-quality product pipeline covering about 50 molecules and has continued to explore immuno-oncology combination therapies with proprietary HANSIZHUANG (anti-PD-1 mAb) as the backbone. To date, the company's launched products include HANLIKANG (rituximab), the first China-developed biosimilar, HANQUYOU (trastuzumab, trade name: HERCESSI™ in the U.S., Zercepac® in Europe), a China-developed mAb biosimilar approved in China, Europe and U.S., HANDAYUAN (adalimumab), HANBEITAI (bevacizumab), HANSIZHUANG (serplulimab, trade name: Hetronifly® in Europe), the world’s first anti-PD-1 mAb for the first-line treatment of SCLC, and HANNAIJIA (neratinib). What’s more, Henlius has conducted over 30 clinical studies for 19 products, expanding its presence in major markets as well as emerging markets.References[1] Robert C. A decade of immune-checkpoint inhibitors in cancer therapy[J].Nature Communications,2020,11(1).[2] Wolchok J D , Saenger Y .The Mechanism of Anti‐CTLA‐4 Activity and the Negative Regulation of T‐Cell Activation[J].The Oncologist,2008,13 Suppl 4(Supplement 4):2-9.[3] Victor T S, Rech A J, Maity A,et al.Radiation and Dual Checkpoint Blockade Activates Non-Redundant Immune Mechanisms in Cancer[J].Nature, 2015, 520(7547).[4] Paul Baas, Arnaud Scherpereel, Anna K Nowak, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021;397(10272):375-386.联系方式媒体：PR@Henlius.com投资者：IR@Henlius.com喜欢本文内容点击下方按钮·分享 ·收藏 ·点赞 ·在看

2025年美国临床肿瘤学会（ASCO）年会将于5月30日-6月3日在美国芝加哥隆重召开。本届学术会议上，复星医药将携手控股子公司复宏汉霖重磅发布近20项最新研究成果，涵盖肺癌、乳腺癌等核心治疗领域，包含芦沃美替尼（FCN-159）、HLX43（PD-L1靶向ADC）、HLX22（抗HER2单抗）、H药汉斯状（抗PD-1单抗，斯鲁利单抗）等创新管线。作为一家创新驱动的全球化医药健康产业集团，复星医药的创新产品聚焦肿瘤（实体瘤、血液瘤）、免疫炎症等核心治疗领域，重点强化抗体/ADC、细胞治疗、小分子核心技术平台，并与产业基金合作布局核药、RNA、基因治疗、AI药物研发等前沿技术，推动更多重磅产品加速研发进程，早日实现商业化。芦沃美替尼（FCN-159）芦沃美替尼（FCN-159）是复星医药自主研发的一款创新型小分子口服药。作为一种高效的MEK1/2选择性抑制剂，芦沃美替尼通过抑制MAPK信号通路中的MEK1/2蛋白活性，阻止肿瘤细胞的增殖和生长。该药物已开展多项针对恶性肿瘤及罕见病的研究，拟主要用于治疗晚期实体瘤、1型神经纤维瘤病、树突状细胞和组织细胞肿瘤、低级别脑胶质瘤等。截至目前，芦沃美替尼片已有2项适应症的上市申请先后获国家药监局受理，并被纳入优先审评程序，分别是用于治疗成人树突状细胞和组织细胞肿瘤、以及治疗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（PN）。该新药用于治疗成人1型神经纤维瘤病于中国境内（不包括港澳台地区，下同）处于III期临床试验阶段，用于治疗低级别脑胶质瘤、颅外动静脉畸形、儿童朗格汉斯组织细胞增生症于中国境内均处于II期临床试验阶段，其中，用于治疗组织细胞肿瘤、无法手术或术后残留/复发的NF1相关的丛状神经纤维瘤成人患者、儿童朗格汉斯组织细胞增生症三项适应症均已被国家药监局药品审评中心纳入突破性治疗药物程序。作为国产MEK抑制剂的代表，芦沃美替尼将填补国内在这些罕见肿瘤治疗方案上的空白，尤其在组织细胞肿瘤等难治性疾病领域具有重要意义。HLX43（PD-L1靶向 ADC）其中HLX43是一款靶向程序性死亡-配体1（PD-L1）的新型ADC候选药物，由全人源IgG1抗PD-L1抗体与创新连接子-拓扑异构酶抑制剂荷载偶联而成，其药物抗体比（drug-to-antibody ratio, DAR）约为8。HLX43兼具毒素精准杀伤和肿瘤免疫作用的复合功能，其毒素不仅能够藉靶点内吞进入肿瘤细胞后进行释放，并在肿瘤微环境中释放后借助旁观者效应进入肿瘤细胞，阻断DNA复制，从而导致肿瘤细胞凋亡。此外，HLX43的PD-L1靶向抗体可激活免疫调节机制，发挥协同抗肿瘤效应。临床前研究表明，HLX43在单药及联合治疗中均展现出显著抗肿瘤活性，有望为PD-1/PD-L1疗法耐药或无效的恶性肿瘤患者提供全新的治疗选择。HLX22（抗HER2单抗）HLX22是一款靶向HER2的创新型单克隆抗体，可结合在HER2的胞外亚结构域IV，但结合表位与曲妥珠单抗有所不同，使得该产品能够与曲妥珠单抗同时结合至HER2，促进HER2二聚体（HER2同源二聚体及HER2/EGFR异源二聚体）的内吞和降解，进而产生更强的HER2受体阻断效果。HLX22联合汉曲优®（曲妥珠单抗，美国商品名：HERCESSI™，欧洲商品名：Zercepac®）治疗HER2阳性胃癌的II期临床研究结果显示，在汉曲优®联用化疗的基础上加入HLX22可提高HER2阳性G/GEJ癌患者一线治疗的生存期和抗肿瘤反应，且安全性可控。目前，HLX22联合曲妥珠单抗及化疗一线治疗HER2阳性晚期胃癌的国际多中心III期临床研究（HLX22-GC-301）分别获得中国、美国、日本和澳大利亚等地药监机构的新药临床试验（IND）许可，并完成首例患者给药。此外，HLX22于2025年获得美国食品药品监督管理局（FDA）授予的孤儿药资格认定（Orphan Drug Designation, ODD），用于胃癌的治疗。继胃癌之后，HLX22与德曲妥珠单抗的联合疗法已拓宽至乳腺癌疾病领域，有望为更多肿瘤患者带来新的治疗选择。H药 汉斯状®（抗PD-1单抗，斯鲁利单抗）H药 汉斯状®为重组人源化抗PD-1单抗注射液（通用名：斯鲁利单抗注射液），是全球首个获批一线治疗小细胞肺癌的抗PD-1单抗，已在中国、欧盟以及多个东南亚国家获批上市。聚焦肺癌和消化道肿瘤，复宏汉霖积极推进H药与公司其他产品的协同以及与创新疗法的联合，截至目前，H药已在中国获批用于治疗鳞状非小细胞肺癌（sqNSCLC）、广泛期小细胞肺癌（ES-SCLC）、食管鳞状细胞癌（ESCC）和非鳞状非小细胞肺癌（nsNSCLC）。H药治疗SCLC也已获得美国FDA和欧盟EC的孤儿药资格认定，并在美国积极推进一项H药对比一线标准治疗阿替利珠单抗的头对头桥接试验。H药的4项关键性临床研究结果分别发表于知名期刊《美国医学会杂志》（JAMA）、《自然-医学》（Nature Medicine）、Cancer Cell和British Journal of Cancer。此外，H药还荣获《CSCO 小细胞肺癌诊疗指南》、《CSCO非小细胞肺癌诊疗指南》、《CSCO 食管癌诊疗指南》、《CSCO免疫检查点抑制剂临床应用指南》和《中国食管癌放射治疗指南》等多部权威指南推荐，为肿瘤临床诊疗提供重要参考。