A RANDOMIZED COMPARATIVE STUDY ASSESSING THE SWITCHING BETWEEN PF-06410293 AND HUMIRA (REGISTERED) IN COMBINATION WITH METHOTREXATE IN PARTICIPANTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS

The study will assess the impact of pharmacokinetics (PK), safety and immunogenicity after switches between PF-06410293 and adalimumab and with continuous dosing with adalimumab in combination with methotrexate in subjects with moderately to severely active rheumatoid arthritis.

开始日期2020-01-13

申办/合作机构

Pfizer Inc.

NCT02480153

/ Completed临床3期

A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY ASSESSING THE EFFICACY AND SAFETY OF PF-06410293 AND ADALIMUMAB IN COMBINATION WITH METHOTREXATE IN SUBJECTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS WHO HAVE HAD AN INADEQUATE RESPONSE TO METHOTREXATE

The study will assess the efficacy, safety, and immunogenicity of PF-06410293 and adalimumab in combination with methotrexate in subjects with moderately to severly active rheumatoid arthritis who have had an inadequate response to methotrexate.
In an additional optional portion of the study, during open label Treatment Period 3 (TP3), a subset of subjects used a Prefilled Pen (PFP) to administer up to 3 injections of their study treatment (PF-06410293) at home.

开始日期2015-06-25

申办/合作机构

Pfizer Inc.

PER-063-14

/ Completed临床3期

A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY ASSESSING THE EFFICACY AND SAFETY OF PF-06410293 AND ADALIMUMAB INCOMBINATION WITH METHOTREXATE IN SUBJECTS WITH MODERATELY TO SEVERELY ACTIVE RHEUMATOID ARTHRITIS WHO HAVE HAD AN INADEQUATE RESPONSE TO METHOTREXATE

开始日期2015-04-07

申办/合作机构

Pfizer Inc.

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项与阿达木单抗生物类似药 (辉瑞制药) 相关的文献（医药）

2024-07-02·EXPERT OPINION ON BIOLOGICAL THERAPY

Industry perspective on regulatory authority (RA) quality reviews of biosimilar applications – an evaluation of RA guidance and expectations for chemical, manufacturing, and controls information through in-depth query analysis

Article

作者: Tennyson, Scott D ; Hufnagel, Heather Rae

PURPOSE:

Evaluate the type and quantity of quality information (i.e. Chemistry, Manufacturing, and Control) requested by the US FDA and EMA in queries pertaining to biosimilar applications.

METHODS:

Numbers/types of queries received following regulatory submissions (FDA/EMA, n = 7/n = 5) for seven biosimilars (PF-filgrastim [Nivestym], PF-rituximab [Ruxience®], PF-trastuzumab [Trazimera®], PF-bevacizumab [Zirabev®], PF-pegfilgrastim [Nyvepria®], PF-adalimumab [Abrilada™/Amsparity®], PF-infliximab [Ixifi]) from a single product portfolio were analyzed considering published regulatory authority (RA) guidance and in relation to sections/subsections of Module 3: Quality from the Common Technical Document regulatory dossier and topics based on keyword assignment.

RESULTS:

Queries were most frequently assigned (FDA/EMA %, range) to Drug Substance Manufacture (subsection 3.2.S.2; 21-35%/13-50%), Control of Drug Substance (3.2.S.4; 3-11%/5-17%), Drug Product Pharmaceutical Development (3.2.P.2; 1-12%/1-15%) and Manufacture (3.2.P.3; 17-41%/2-13%), and Analytical Similarity (3.2.R; 4-21%/4-20%). The proportion of Drug Substance and Drug Product queries was significantly different between RAs (n1 = 952, n2 = 468, p-value <0.001; two-sample proportion z-test). Topic assignments included: Control (12-27%/12-28%), Manufacturing (56-72%/34-66%), Stability (1-12%/2-24%), Biosimilarity (5-16%/5-25%), and Container Closure (0-3%/0-9%).

CONCLUSION:

The focus of both RAs on topics related to manufacturing and controls is valuable in understanding expectations for scientific and technical content related to gaining biosimilar approval.

2023-11-01·Journal of comparative effectiveness research

Navigating adalimumab biosimilars: an expert opinion

Review

作者: Habauzit, Caroline ; Abitbol, Vered ; Benkhalifa, Salim ; Marotte, Hubert

The patent expiry of Humira ® in 2018 opened up the current European market to eight adalimumab biosimilars – (in alphabetical order) Amgevita ® , Amsparity ® , Hulio ® , Hukyndra ® , Hyrimoz ® , Idacio ® , Imraldi ® and Yuflyma ® – for the treatment of various immune and inflammatory conditions. Amjevita, Hadlima ® , Hyrimoz and Yuflyma have recently become available in the USA, with others expected to reach this market in 2023 as the US patent protection for Humira ends. Although adalimumab biosimilars demonstrate efficacy, safety and immunogenicity similar to the originator, they may differ in product excipient(s) and preservatives, along with their device type(s). Physicians may find it both difficult and time consuming to navigate their way among the array of available adalimumab biosimilars when they need to make a treatment decision. This article explores the characteristics of various adalimumab biosimilars to help clinicians navigate the various options available across Europe and the USA. In addition to drug selection, effective patient–physician communication is needed to nurture realistic patient expectations and minimise potential nocebo effects when prescribing biosimilars.

2023-09-01·The Lancet. Rheumatology

Multiple switching between the biosimilar adalimumab PF-06410293 and reference adalimumab in patients with active rheumatoid arthritis: a phase 3, open-label, randomised, parallel-group study

Article

作者: Lakhanpal, Sharad ; Alvarez, Daniel F ; Cronenberger, Carol ; Fleischmann, Roy M ; Ianos, Claudia Ana ; Cox, Donna S ; Saikali, Wassim ; Wang, Karen ; Zhang, Wuyan

BACKGROUND:

An adalimumab biosimilar with an interchangeability designation could increase access to effective treatment for more patients. We aimed to assess the interchangeability of adalimumab biosimilar PF-06410293 (adalimumab-afzb) and reference adalimumab using a multi-switch study design.

METHODS:

We did an open-label, randomised, parallel-group study at 61 community (n=29), hospital (n=12), and academic (n=20) sites in ten countries (Bulgaria, Bosnia and Herzegovina, Czech Republic, Lithuania, Poland, Russia, Serbia, South Africa, Ukraine, and USA). Eligible patients were aged 18-70 years and met the 2010 American College of Rheumatology-European League Against Rheumatism classification criteria for rheumatoid arthritis for at least 4 months with moderately to severely active rheumatoid arthritis, based on their physician's evaluation. Eligible patients had been receiving methotrexate for at least 12 weeks and been on a stable dose for at least 4 weeks before the first dose of study medication. All patients received subcutaneous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks) for 10 weeks before randomisation. At week 10, patients were randomly assigned (1:1) to either three switches between subcutaneous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks) and adalimumab-afzb (40 mg/0·8 mL [50 mg/mL] every 2 weeks; switching group), or continuous dosing with subcutanous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks; non-switching group) with stratification by bodyweight groups. Patients, investigators, and site personnel were not masked to treatment allocation. Primary endpoints were maximum observed serum concentration (C_max) and area under plasma concentration-time curve (AUC_τ) during weeks 30-32 in the pharmacokinetic population. Interchangeability was based on geometric mean ratios and corresponding 90% CIs within prespecified equivalence margins of 80-125% for both primary endpoints. Safety was analysed in all patients who received at least one dose of adalimumab-afzb or reference adalimumab. This trial is registered with ClinicalTrials.gov, NCT04230213.

FINDINGS:

Of the 569 patients assessed for eligibility between Jan 13, 2020, and June 22, 2021, 445 were enrolled, and 427 completed the first 10 weeks and were randomly assigned (213 to the switching group and 214 to the non-switching group). Participants had a median age of 56 years (IQR 46-63), 354 (83%) of 427 patients were women and 73 (17%) were men, and 422 (99%) were White. In the pharmacokinetic population (n=380), no clinically meaningful differences were observed in mean steady-state pharmacokinetic parameters between the switching and non-switching groups (geometric mean AUC 2237 μg × h/mL in the switching group and 2125 μg × h/mL in the non-switching group; C_max 8·21 μg/mL in the switching group and 8·00 μg/mL in the non-switching group). Geometric mean ratios and 90% CIs for AUC_τ (105·31, 89·16-124·39) and C_max (102·56, 89·78-117·17) were within prespecified equivalence margins. No meaningful differences were observed in the proportion of patients who had serious adverse events (three [1%] of 213 patients in the switching group vs eight [4%] of 214 patients in the non-switching group), grade 3 or higher adverse events of special interest, discontinuations due to adverse events (eight [4%] vs nine [4%]), or immunogenic reactions in antidrug antibody-positive patients. No deaths were reported during the study.

INTERPRETATION:

The risk of multiple switches between reference adalimumab and adalimumab-afzb with respect to diminished efficacy (using pharmacokinetics as a surrogate) or safety is not greater than the risk of using reference adalimumab alone.

FUNDING:

Pfizer. VIDEO ABSTRACT.

项与阿达木单抗生物类似药 (辉瑞制药) 相关的新闻（医药）

2025-04-29

·医药投资部落

降本增效持续优化，荣昌生物大拐点确认

2025年4月28日，荣昌生物如期发布了2025年的一季报。如果说，2024全年财报的优异表现，是荣昌生物传递给市场的一个转折性信息：公司已经进入到了一个全新的发展阶段；那么2025年的一季报，则可以视为是对荣昌生物上述经营拐点的有效确认。关键指标全面提升2025年一季度，荣昌生物的创新药销售继续保持高速增长趋势，公司营业收入达到了5.3亿元，相比于去年同期增速高达59.2%。一般来说，创新药上市之后的几年，医生和患者对药品的疗效缺乏基本的了解和信任，需要药企通过学术推广和医患教育逐步打开市场，很多创新药企业的商业化都受困于这个阶段而无法突破。2024年，荣昌生物的全年销售数据大幅提升58.5%，可以认为公司已经基本完成新药上市之后最为艰难的市场导入期，成功进入到销售持续快速放量的新阶段。2025年一季度，销售数据继续保持59.2%的高速增长，是对上述趋势的进一步有效确认。与此同时，和收入端的高增长相得益彰的，是荣昌生物通过在内部不断践行精益管理战略，在成本端成功实现了持续的费用管控和效率提升。2025年一季度，荣昌生物的销售费用率为47.7%，相比于去年同期下降了9个百分点，比去年全年水平也下降了7.6个百分点，成本端的指标呈现持续优化的趋势。在这种显著的降本增效作用下，荣昌生物2025年一季度的毛利率达到了83.3%，相比去年同期提升5.8个百分点，这个毛利率水平，足以跻身国内创新药企业的一线行列。在中国创新药行业，一家药企可以达到的上限，既取决于其创新研发能力，更取决于新药上市之后的商业化能力。荣昌生物作为一家在研发领域已经证明自身卓越实力的创新药企业，其商业化销售体系也正在快速地成熟。目前，公司自身免疫商业化团队已超过800人，已经完成超过1000家医院的药品准入；肿瘤科商业化团队约500人，也已经完成超过1000家医院的药品准入。综合最近几个季度的数据来看，公司对于1400多人的销售团队的运营和管理已经越发的得心应手，这是荣昌生物从Biotech向BioPharma成功跃迁的显著标志之一。可以说，在商业化领域，荣昌生物展现出了与一家行业头部企业相匹配的核心能力。这种出色的商业化能力带来的一个良好的结果，是企业的现金流的持续好转。在2024年，虽然公司整体净利润仍然为负，但是其实荣昌生物已经实现了商业化盈利：公司通过创新药产品销售产生的现金流，已经基本可以覆盖药品生产、销售、和行政运营等成本，净利润为负的主要因素是研发费用的投入。2025年一季度，公司的亏损进一步收窄，相比于去年同期减亏近1亿元，同比亏损幅度降低27.2%，同时继续维持了商业化盈利的良好局面。对于此前外界一直关注的公司现金流的问题，这是荣昌生物用实打实的业绩数据，做出的最有说服力的回答。管线研发高歌猛进在创新药商业化持续取得不俗业绩的同时，荣昌生物的管线研发同样成绩斐然。泰它西普大放异彩2025年4月8日，第77届美国神经病学学会（AAN）年会在圣地亚哥会议中心举行，荣昌生物自主研发的BLyS/APRIL双靶点融合蛋白创新药泰它西普（Telitacicept，RC18，商品名：泰爱®）用于治疗全身型重症肌无力（gMG）Ⅲ期研究结果，以“最新突破性研究”口头报告惊艳亮相。数据显示，泰它西普治疗24周后，98.1%的患者重症肌无力日常活动评分（MG-ADL）改善≥3分，87%的患者定量重症肌无力评分（QMG）改善≥5分，具有显著的临床意义。在已完成全身型重症肌无力Ⅲ期临床研究的药物中，泰它西普的MG-ADL应答率数据最高，有望改写该疾病领域的全球治疗格局。目前，泰它西普在gMG领域已获得中国NMPA纳入突破性治疗品种、美国FDA孤儿药资格和快速通道资格三项认定，成为全球gMG领域极具潜力的创新治疗药物。此外，泰它西普已经布局了类风湿性关节炎、系统性红斑狼疮、IgA肾病和干燥综合征等多个重磅适应症，且在多项临床试验中显示出较好的治疗前景。2025年，泰它西普的重症肌无力适应症有望在中国获批，同时IgA肾病、干燥综合征适应症预计将于2025年下半年提交上市申请（BLA）。随着适应症的不断拓展，泰它西普作为公司的核心增长引擎，其未来的增量仍然有极大的想象空间，这款药物将在很长一段时间成为荣昌生物的“现金奶牛”。如果说国内市场的优异表现是荣昌生物的基本盘，那么以泰它西普为代表的管线出海预期，则是荣昌生物潜在的基本面催化剂和市值放大器。近年来，全球自身免疫疾病（自免）领域的BD交易呈现爆发式增长，自免赛道正成为众多跨国药企越来越重视的一个战略方向。目前，围绕着T淋巴细胞相关的自身免疫疾病，已经诞生了阿达木单抗、英夫利昔单抗、依那西普等一系列重磅炸弹药物，全球合计销售额超过400亿美元。同样和自身免疫疾病的发生与进展密切相关的B淋巴细胞方向，目前还没有诞生一个爆款产品。BLyS和APRIL靶点在B淋巴细胞的作用机制中十分关键，作为全球首款BLyS和APRIL双靶点生物制剂，泰它西普已经完全具备了成为自免领域一款广谱性大药的潜力，这也让广大投资者对它的BD有了一定的期待。维迪西妥单抗的新适应症除了泰它西普有可能在2025年获批新的适应症，荣昌生物的ADC药物维迪西妥单抗（RC48，爱地希®），同样有望在2025年收获新的适应症。2024年10月15日，维迪西妥单抗一项新适应症的上市申请，获得国家药品监督管理局药品审评中心（CDE）受理，同时CDE同意纳入优先审评审批程序，该适应症为：用于既往接受过曲妥珠单抗或其生物类似物和紫杉类药物治疗的HER2 阳性（HER2免疫组织化学检查结果为3+或FISH+）存在肝转移的晚期乳腺癌患者。在第47届圣安东尼奥乳腺癌研讨会（SABCS）上，荣昌生物首次对外公布了维迪西妥单抗治疗HER2阳性存在肝转移的晚期乳腺癌患者Ⅲ期临床研究数据。根据独立审查委员会（IRC）评估，与对照组相比，维迪西妥单抗显著延长了患者的无进展生存期（PFS），疾病进展或死亡风险降低了44%。这是全球首个证实HER2 ADC在HER2阳性存在肝转移的晚期乳腺癌患者中，取得阳性结果的确证性Ⅲ期研究，对于存在肝转移的晚期乳腺癌的治疗具有突破性的意义。根据对于审批时间的估算，维迪西妥单抗的这个新适应症有望在2025年上半年获批。除了上述适应症的突破以外，荣昌生物同时在积极探索维迪西妥单抗在多个领域的治疗前景。在2025年一季度举行的欧洲泌尿外科学会（EAU）年会上，维迪西妥单抗就有5项研究入选，涉及尿路上皮癌、非肌层浸润性膀胱癌等多个适应症。此外，荣昌生物也在积极尝试维迪西妥单抗与PD-1、化疗、双特异性抗体等联合用药方案，力求最大程度地拓展这款首个国产ADC药物的临床使用场景，在造福更多患者的同时，也不断丰富这款药物的商业化想象空间。在研管线实力雄厚作为一家研发实力居于行业头部水平的创新药公司，在成功上市泰它西普和维迪西妥单抗这两款重磅药物之后，荣昌生物的在研管线中还有多款极具竞争力的创新药物分子。RC28是荣昌生物开发的用于治疗眼科疾病的全球首创VEGF/FGF双靶标融合蛋白药物，该管线有望成为荣昌生物第三款进入商业化阶段的创新药。RC28用于糖尿病性黄斑水肿（DME）患者的Ⅲ期研究患者入组已于 2024 年第一季度完成入组，预计2025年下半年有望递交国内上市申请；此外，湿性年龄相关性黄斑变性（wAMD）适应症Ⅲ期研究患者入组已于2024年完成，预计2026年上半年在国内递交上市申请。RC88是荣昌生物自主研发的新型间皮素（MSLN）靶向ADC药物，用于治疗 MSLN 阳性实体瘤。靶向MSLN的ADC目前是ADC领域的一个热门方向，此前，跨国药企辉瑞以超过10亿美元的总交易金额，引进了中国药企和铂医药的一款MSLN ADC在研管线。荣昌生物的RC88已经于2024年1月获美国食品药品监督管理局（FDA）授予的快速通道认定（FTD），整体研发进度居于行业前列。此外，荣昌生物还有一款在研的新型ADC药物RC278，其靶点相关信息一直处于保密状态，但是目前已经完成了临床前研究工作，即将进入临床试验阶段。整体而言，荣昌生物在研管线的实力极为雄厚，这一部分资产的潜在价值，目前可能还没有被市场所充分挖掘和认知。创新药反转行情的领头羊进入2025年以来，对于创新药的支持政策不断出台，创新药产业的重要战略地位逐步确立，二级市场投资情绪也在悄然改善，已经在寒冬中煎熬许久的创新药板块，迎来了一轮久违的“小阳春”。在这轮创新药板块的反转行情中，荣昌生物是当之无愧的“领头羊”：从2025年1月上旬到2025年4月下旬，在3个多月的时间内，荣昌生物的股价气势如虹，从25元/股左右一举突破55元/股，一举实现了翻倍行情。这种给力的股价表现背后，既是行业积极因素的共振，更是投资者对于荣昌生物基本面显著改善的高度认可。以硬核的原始创新能力打造“FIC”或者“BIC”管线，以科学的精益管理构筑高效的商业化体系，荣昌生物通过多年不懈的努力，已经成功在中国市场实现了创新药价值闭环。随着更多研发进展的落地，随着精益管理战略的持续推进和优化，我们有理由对这家励精图治的国产创新药标杆企业，持有更为宏大的期待。

财报

2025-03-26

·抗体圈

专利悬崖下的王者黄昏：Humira 生物类似药与新疗法如何重塑免疫治疗格局

导语：曾经年销 220 亿美元的药王 Humira 正经历 “退位潮”。随着专利保护到期，生物类似药的价格战与新疗法的崛起正加速改写免疫治疗版图。当医生开始用 “adalimumab” 通用名处方，当 CVS 将原研药移出报销目录，这场药王退位战已演变为一场关乎行业规则的深度变革。一、专利到期后的市场震荡：从 “药王” 到 “平民药” Humira（阿达木单抗）曾连续多年稳坐全球药王宝座，2021 年销售额突破 220 亿美元。但 2023 年专利到期后，其市场地位迅速崩塌：销售额腰斩：2024 年全球销售额降至 98 亿美元，美国市场份额从 80% 跌至 62%。生物类似药井喷：12 款 Humira 生物类似药涌入市场，Amgen 的 Amjevita、Sandoz 的 Hyrimoz 等通过低价策略抢占份额，其中 Amjevita 2024 年销售额同比激增 22% 至 7.61 亿美元。支付方倒逼转型：CVS Caremark 将 Humira 移出报销目录后，Hyrimoz 处方量暴增，其 2024 年价格仅为原研药的 20%。二、生物类似药的价格战与渠道博弈生物类似药的竞争核心在于价格与渠道：价格屠夫策略：Sandoz 与 CVS 合作推出私有品牌 Hyrimoz，定价仅为原研药的 20%；辉瑞 Abrilada 以 539 美元 / 两剂成为市场最低价。处方权争夺：医生开始使用通用名 “adalimumab” 开具处方，由保险公司决定具体品牌。风湿病学家处方中，生物类似药占比从 2023 年的 3% 升至 2024 年的 10%。渠道分层：诺华 Cosentyx、强生 Stelara 等新疗法通过更高疗效（如银屑病皮肤清除率达 90%）吸引高净值患者，而生物类似药主攻价格敏感型市场。三、专科医生的处方革命：从 “忠诚” 到 “理性” 不同专科医生对生物类似药的接受度差异显著：风湿病学：生物类似药占比已达 38%，Hyrimoz 以 33% 的份额领跑，预计 2025 年原研药份额将降至 12%。皮肤病学：生物类似药占比仅 4%，因患者更倾向选择 J&J 的 Stelara（IL-12/23 抑制剂）等新一代药物，其皮肤清除率比 Humira 高 30%。胃肠病学：生物类似药占比 6%，但新指南推荐优先使用 Takeda 的 Entyvio（α4β7 整合素抑制剂）等靶向疗法。 “医生更关注疗效与患者体验，而非品牌忠诚度。”Spherix Global Insights 专家 Lynn Price 指出，“生物类似药的成功源于支付方压力，而非临床优势。”四、新疗法的逆袭：从 “me-too” 到 “best-in-class” 新疗法的崛起加速了 Humira 的衰落：机制创新：IL-17 抑制剂（Cosentyx）、IL-23 抑制剂（Skyrizi）等精准靶向疗法，将银屑病治疗有效率从 60% 提升至 85%。口服药冲击：辉瑞的 JAK 抑制剂 Xeljanz（2024 年销售额 18 亿美元）以每日一片的便捷性分流轻中度患者。联合疗法趋势：礼来的 Taltz（IL-17A 抑制剂）与甲氨蝶呤联用，使类风湿关节炎患者达标率提升 40%。五、行业启示：药王退位背后的生态重构 Humira 的衰落揭示出三大行业趋势：专利悬崖效应加剧：未来 5 年，全球将有超 2000 亿美元专利药到期，生物类似药市场规模将突破 1500 亿美元。支付方话语权增强：美国医保通过 “参考定价” 等策略，推动生物类似药市场渗透率从 10% 升至 30%。创新药定价逻辑生变：新疗法需通过 “疗效溢价” 而非 “市场独占” 维持高价，如诺华 Kisqali 凭借 OS 延长 4 个月定价 15 万美元 / 年。六、未来展望：生物类似药与创新药的共生时代尽管生物类似药短期内抢占市场，但长期来看：生物类似药面临同质化竞争：12 款阿达木单抗生物类似药将陷入价格战，预计 2026 年平均价格将降至原研药的 15%。创新药聚焦差异化：基因泰克的 Tecentriq（PD-L1 抑制剂）、渤健的 Zeposia（S1P 调节剂）等通过 “多适应症布局 + 精准医疗” 开辟新赛道。行业整合加速：CMO 企业如 Catalent 通过收购扩展生物类似药产能，而 Biogen 等药企则剥离传统管线，聚焦基因治疗等高壁垒领域。七、结语Humira 的退位不是终点，而是免疫治疗新时代的起点。当生物类似药将单抗价格拉入 “千元时代”，当创新疗法重新定义疗效标准，这场药王黄昏战正深刻改变全球医药产业的价值逻辑。而患者，终将成为这场变革最大的受益者 —— 在疗效与价格之间，他们第一次拥有了真正的选择权。参考来源：https://www.biospace.com/business/humira-biosimilars-gain-ground-as-doctors-adjust-and-new-therapies-rise 识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

生物类似药专利到期

2025-02-10

·复宏汉霖

产品速递 | 复宏汉霖PD-L1靶向ADC HLX43II期研究完成首例受试者给药

近日，复宏汉霖（2696.HK）宣布，公司基于与宜联生物的合作开发的靶向程序性死亡-配体1（PD-L1）的新型抗体偶联药物（ADC）注射用HLX43在复发/转移性食管鳞癌患者中开展的II期临床研究（HLX43-ESCC201）于中国完成首例受试者给药。目前，全球尚无同类靶向PD-L1的ADC产品获批上市，仅有SGE-PDL1V（来自辉瑞）即将启动临床III期试验，HLX43为全球第二款进入临床阶段的靶向PD-L1的ADC产品。近年来，以抗PD-1/L1抗体为代表的免疫检查点抑制剂（ICI）促进了肿瘤免疫治疗的高速发展，成为肿瘤患者各线治疗的主要手段之一。然而，部分PD-L1阳性患者对该疗法无响应，或者出现耐药[1]。对于免疫治疗耐药或经免疫治疗等标准治疗失败后的患者人群，尚缺少有效的后线治疗方案，亟待探索更前沿的新型治疗方案，进一步提高患者的临床获益。ADC作为当下肿瘤治疗中疗效最突出的新型疗法，已在乳腺癌、肺癌、食管癌、胃癌等多项实体瘤中展现出初步的治疗潜力，成为重要的探索方向[2]。而PD-L1在非小细胞肺癌、结直肠癌、三阴性乳腺癌、鳞状细胞癌等多种癌种中均有表达，且在正常组织中的表达有限，使其成为开发ADC药物的潜力靶点，为肿瘤治疗带来新的途径[3]。 HLX43为复宏汉霖首批进入临床阶段的ADC产品之一，旨在解决PD-1/L1免疫疗法不响应或耐药问题，填补更多晚期/转移性实体瘤患者未满足的临床需求。HLX43兼具抗体分子的高度靶向性和细胞毒素的强大杀伤力，可通过与肿瘤细胞表面PD-L1 抗原特异性结合，经内吞后释放小分子毒素，从而发挥抗肿瘤作用。2023年，HLX43治疗晚期/转移性实体瘤的I期临床试验申请先后获中国国家药品监督管理局（NMPA）和美国食品药品管理局（ FDA）批准，并于2023年11月在中国境内完成首例患者给药。2024年12月，HLX43单药或联合治疗晚期/转移性实体瘤的Ib/II期临床试验申请获NMPA批准。临床前研究及I期临床研究提示，HLX43在PD-1/PD-L1单抗耐药的非小细胞肺癌、宫颈癌、食管鳞癌、肝癌等多个瘤种中显示出显著疗效，且耐受性良好，临床前研究数据于2023欧洲肿瘤内科学会（ESMO）大会以壁报形式进行展示。基于此，复宏汉霖计划于近期启动HLX43在包括食管鳞癌、宫颈癌、肝细胞癌、鼻咽癌、头颈部鳞癌、非小细胞肺癌等实体瘤中的II期临床试验，以进一步评HLX43的疗效和安全性。未来，复宏汉霖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，加速推动更多前沿治疗方案的研究和开发，为全球患者带来更多高质量、可负担的创新治疗方案。【参考文献】 [1] Attili I, et al. Strategies to overcome resistance to immune checkpoint blockade in lung cancer[J]. Lung cancer: Journal of the International Association for the Study of Lung Cancer, 2021(154-):154. [2] He J, Zeng X, Wang C, Wang E, Li Y. Antibody-drug conjugates in cancer therapy: mechanisms and clinical studies. MedComm (2020). 2024 Jul 28;5(8):e671. [3] Kwan B, et al. 783 SGN-PDL1V, a novel, investigational PD-L1-directed antibody-drug conjugate for the treatment of solid tumors[J]. 2021. 关于HLX43-ESCC201 本研究为评估不同剂量HLX43在经一线标准治疗失败或不可耐受毒性的复发/转移性食管鳞癌患者中的有效性和安全性的II期临床试验。筛选合格的受试者将接受每 3 周一次（Q3W）HLX43治疗。本研究主要目的是评估HLX43 在复发/转移性食管鳞癌中的临床疗效。次要目的是评估安全性和耐受性、药代动力学特征及免疫原性、和潜在预测性生物标志物。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，4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50多个分子，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，欧盟商品名：Hetronifly®）以及汉奈佳®（奈拉替尼）。公司亦同步就16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 a Phase 2 Clinical Trial of Henlius’ PD-L1-Targeting ADC HLX43 Recently, Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first subject has been dosed for a phase 2 clinical trial of HLX43 for Injection (HLX43-ESCC201), the novel Programmed Death-Ligand 1 (PD-L1)-targeting antibody-drug conjugate (ADC) that developed by the company based on the collaboration with MediLink Therapeutics, for the treatment of patients with recurrent/metastatic esophageal squamous cell carcinoma (ESCC). At present, no PD-L1 targeting ADC has been approved for marketing globally, and only SGN-PDL1V from Pfizer is about to innitiate a Phase 3 clinical trial. HLX43 is the second PD-L1-targeting ADC to enter clinical trial globally. Immune checkpoint inhibitors represented by PD-1/PD-L1 monoclonal antibodies have emerged in recent years and revolutionised all lines of treatment for tumour patients. However, there are still many patients with positive PD-L1 expression who do not respond to or develop resistance to PD-1/PD-L1-targeted therapy[1]. To date, there has been no subsequent-line treatment for patients who are resistant to PD-1/L1 immunotherapy or failed to benefit from the standard treatments including immunotherapy, indicating a significant unmet medical need to further improve the clinical benefits for these patients. As a novel targeting therapy with the most prominent anti-tumour efficacy, ADCs have shown preliminary therapeutic potential in the treatment of multiple advanced solid tumours, such as breast cancer(BC), lung cancer(LC), esophageal cancer(EC) and gastric cancer(GC) ,making it a promising therapeutic in solid tumours[2]. PD-L1 is expressed in patients across a broad spectrum of tumour types including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), triple negative breast cancer (TNBC), squamous cell carcinoma and displays limited expression on normal tissues, highlighting the potential of PD-L1 as a target for ADCs, which may bring new options for cancer treatment[3]. HLX43 is one of the first ADC candidates of Henlius to enter into clinical development. Combining the selectivity of targeted monoclonal antibodies with the highly potent cytotoxic agent, HLX43 could exert anti-tumour effects through specific binding to the PD-L1 expressed on the surface of tumour cells and release cytotoxic payloads after internalisation by the cancer cells. In 2023, the application for phase 1 clinical trial of HLX43 for the treatment of advanced/metastatic solid tumours was approved by the China National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA), respectively. And the first patient has been dosed in this trial in November 2023 in the Chinese Mainland. In December 2024, the application for a phase 1b/2 clinical trial of HLX43 for the monotherapy or combination therapy of advanced/metastatic solid tumours has been approved by the NMPA. Several non-clinical studies and the phase 1 clinical trial have shown that, HLX43 has good anti-tumour effects and a favorable tolerability profile in non-small cell lung cancer (NSCLC) , cervical cancer (CC), ESCC, hepatocellular carcinoma (HCC), and other tumour types that were PD-1/L1 mAb-resistant. The results of the pre-clinical studies were published as poster presentation at the 2023 European Society of Medical Oncology (ESMO) Congress. Based on this, Henlius plans to initiate phase 2 clinical trials of HLX43 for potential solid tumour indications including ESCC, CC, HCC, nasopharyngeal carcinoma(NPC), head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC)，to further evaluate the efficacy and safety of HLX43 in patients. With a particular focus on addressing the unmet medical needs, Henlius will further take efforts to accelerate the R&D of more cutting-edge therapeutic options and promote the layout of our innovative portfolio based on the company’s competitive edge of an integrated antibody drug R&D platform, bringing more high-quality and affordable therapeutics for patients worldwide. About HLX43-ESCC201 This study is a phase 2 clinical trial designed to evaluate the efficacy and safety of different doses of HLX43 in patients with recurrent/metastatic esophageal squamous cell carcinoma (ESCC) who have failed or are intolerant to first-line standard treatment. Eligible subjects will receive HLX43 every 3 weeks (Q3W). The primary objective of this study is to assess the clinical efficacy of HLX43 in recurrent/metastatic ESCC. Secondary objectives include evaluating safety and tolerability, pharmacokinetic characteristics and immunogenicity, and potential predictive biomarkers. About Henlius Henlius (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 4 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 over 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 the EU), 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 16 products, expanding its presence in major markets as well as emerging markets. 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

抗体药物偶联物免疫疗法临床3期临床2期临床1期

100 项与阿达木单抗生物类似药 (辉瑞制药) 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	阿达木单抗生物类似药 (辉瑞制药)	L04AB04	DB00051

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
多关节型幼年特发性关节炎	澳大利亚	Pfizer Australia Pty Ltd.	2021-02-22
中轴性脊柱关节炎	欧盟	Pfizer Europe MA EEIG	2020-02-13
中轴性脊柱关节炎	冰岛	Pfizer Europe MA EEIG	2020-02-13
中轴性脊柱关节炎	列支敦士登	Pfizer Europe MA EEIG	2020-02-13
中轴性脊柱关节炎	挪威	Pfizer Europe MA EEIG	2020-02-13
附着点炎相关关节炎	欧盟	Pfizer Europe MA EEIG	2020-02-13
附着点炎相关关节炎	冰岛	Pfizer Europe MA EEIG	2020-02-13
附着点炎相关关节炎	列支敦士登	Pfizer Europe MA EEIG	2020-02-13
附着点炎相关关节炎	挪威	Pfizer Europe MA EEIG	2020-02-13
化脓性汗腺炎	欧盟	Pfizer Europe MA EEIG	2020-02-13
化脓性汗腺炎	冰岛	Pfizer Europe MA EEIG	2020-02-13
化脓性汗腺炎	列支敦士登	Pfizer Europe MA EEIG	2020-02-13
化脓性汗腺炎	挪威	Pfizer Europe MA EEIG	2020-02-13
非感染性前葡萄膜炎	欧盟	Pfizer Europe MA EEIG	2020-02-13
非感染性前葡萄膜炎	冰岛	Pfizer Europe MA EEIG	2020-02-13
非感染性前葡萄膜炎	列支敦士登	Pfizer Europe MA EEIG	2020-02-13
非感染性前葡萄膜炎	挪威	Pfizer Europe MA EEIG	2020-02-13
小儿克罗恩病	欧盟	Pfizer Europe MA EEIG	2020-02-13
小儿克罗恩病	冰岛	Pfizer Europe MA EEIG	2020-02-13
小儿克罗恩病	列支敦士登	Pfizer Europe MA EEIG	2020-02-13

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04230213 (CTgov)	临床3期	类风湿关节炎	455	Adalimumab+Humira (Switching Arm: Humira and PF-06410293 (Adalimumab))	鑰鏇淵襯觸構顧艱願壓(鹽繭遞範襯繭憲構築觸) = 簾鹹餘淵膚齋願範糧蓋淵積鹹鏇鹽網醖築蓋夢 (襯獵壓顧範顧壓鹽齋壓, 97) 更多	-	2022-08-22
				Humira (Adalimumab) (Non-switching Arm: Humira (Adalimumab))	鑰鏇淵襯觸構顧艱願壓(鹽繭遞範襯繭憲構築觸) = 選繭鹽積鹹蓋蓋蓋製繭淵積鹹鏇鹽網醖築蓋夢 (襯獵壓顧範顧壓鹽齋壓, 97) 更多
NCT02480153 (not available, EULAR2020)	临床3期	类风湿关节炎	597	ADL-PF	觸遞選築積餘齋壓範構(鬱願窪壓簾鬱鹽壓餘遞) = 夢鑰範鑰鬱積觸鑰築顧選鏇餘鬱網蓋艱鑰醖繭 (淵積製鹹築遞願簾艱願 )	积极	2020-06-03
				ADL-EU	觸遞選築積餘齋壓範構(鬱願窪壓簾鬱鹽壓餘遞) = 窪遞膚鏇鹽膚願膚簾繭選鏇餘鬱網蓋艱鑰醖繭 (淵積製鹹築遞願簾艱願 )
NCT02480153 (Pubmed \| Arthritis Res Ther) 人工标引	临床3期	类风湿关节炎	597	PF-06410293	艱範餘顧築鏇膚襯範觸(範鑰獵衊繭膚窪鹽醖膚) = 簾繭鹹顧簾鏇鏇蓋顧齋艱鹽築齋淵艱齋願製願 (齋鏇鑰齋鏇鏇網襯顧襯 )	相似	2018-08-15
				adalimumab	艱範餘顧築鏇膚襯範觸(範鑰獵衊繭膚窪鹽醖膚) = 網顧鹽選築製襯蓋觸網艱鹽築齋淵艱齋願製願 (齋鏇鑰齋鏇鏇網襯顧襯 )
EULAR2018	N/A	类风湿关节炎	597	PF-06410293	積範艱齋餘願蓋蓋獵鑰(顧製獵鬱構選鬱蓋獵鑰) = 選膚繭艱鹽糧窪鏇鬱鏇憲築獵網衊網餘顧艱簾 (願選鏇觸願憲壓鏇築簾 ) 更多	-	2018-06-13
				ADA-EU	積範艱齋餘願蓋蓋獵鑰(顧製獵鬱構選鬱蓋獵鑰) = 獵淵淵鑰蓋襯範淵衊淵憲築獵網衊網餘顧艱簾 (願選鏇觸願憲壓鏇築簾 ) 更多
NCT02480153 (REFLECTIONS B538-02 \| not available, CTgov)	临床3期	类风湿关节炎	597	PF-06410293 (Period 1: PF-06410293)	獵觸鹽鬱醖選製蓋觸艱 = 顧繭觸鹽築鏇醖繭築觸蓋餘壓憲鹹範衊鏇衊遞 (築製淵鑰鏇網餘獵糧積, 構鹽鬱築觸鬱製鏇鏇鑰 ~ 餘窪獵衊淵範鏇餘鬱製) 更多	-	2017-09-26
				Adalimumab (Period 1: Adalimumab-EU)	獵觸鹽鬱醖選製蓋觸艱 = 製齋觸築鹽蓋遞艱顧蓋蓋餘壓憲鹹範衊鏇衊遞 (築製淵鑰鏇網餘獵糧積, 觸鹽襯網蓋網艱衊糧願 ~ 憲壓膚夢餘鬱積窪選壓) 更多