Ipilimumab biosimilar (Shanghai Henlius)

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