This research study is being done to evaluate the safety and effectiveness of sacituzumab govitecan with trastuzumab (Herceptin, Herceptin Hylecta, or trastuzumab biosimilar) in metastatic HER2+ breast cancer.
The names of the study drugs used in this research study are:
* Sacituzumab govitecan (a type of antibody-drug conjugate)
* Trastuzumab (Herceptin) (a type of monoclonal antibody)
* Trastuzumab and Hyaluronidase-oysk (Herceptin Hylecta) (a type of recombinant monoclonal antibody)
* Trastuzumab biosimilar drug

开始日期2023-11-20

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+1]

NCT04893109

/ Recruiting临床2期IIT

A Randomized Phase II Trial of Adjuvant Trastuzumab Emtansine (T-DM1) Followed by Subcutaneous Trastuzumab Versus Paclitaxel in Combination with Subcutaneous Trastuzumab for Stage I HER2-positive Breast Cancer (ATEMPT 2.0)

This research study is studying how well newly diagnosed breast cancer that has tested positive for a protein called HER2 responds using one of two different combination of HER2-directed therapies as a treatment after surgery.
The name of the study drugs involved are:
* Trastuzumab-emtansine (T-DM1, Kadcyla)
* Trastuzumab SC (Herceptin Hylecta)
* Paclitaxel

开始日期2021-06-16

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+1]

NCT03498521

/ Completed临床2期

A Phase II, Randomized, Active-Controlled, Multi-Center Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Guided by Genomic Profiling Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site Who Have Received Three Cycles of Platinum Doublet Chemotherapy

This study will compare the efficacy and safety of molecularly-guided therapy versus standard platinum-containing chemotherapy in participants with poor-prognosis cancer of unknown primary site (CUP; non-specific subset) who have achieved disease control after 3 cycles of first-line platinum based induction chemotherapy.

开始日期2018-07-10

申办/合作机构

Hoffmann-La Roche, Inc.

[+1]

100 项与曲妥珠单抗/透明质酸酶相关的临床结果

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100 项与曲妥珠单抗/透明质酸酶相关的转化医学

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100 项与曲妥珠单抗/透明质酸酶相关的专利（医药）

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项与曲妥珠单抗/透明质酸酶相关的文献（医药）

2023-01-01·Cancer treatment and research communications

Neoadjuvant Trastuzumab and Pertuzumab in Combination with Standard Chemotherapy for HER2-Positive Early Breast Cancer: Real-World Practice in Cuba

Article

作者: Miguel, Karen López ; Prado, Yenia I Díaz ; Carrasco, Julien Martínez ; Medina, Elías A Gracia ; Caballero, Brenda Benítez ; Tul, Luis E Alsina ; Gutiérrez, Zaili Aleaga ; Bernardo, María de la Caridad Campos ; Torres, Keytia Peña ; Fernández, Braulio Mestre ; Montero, Yoandri Calderón ; Ortiz, Mónica Ramos ; Rodríguez, Luis E Martín ; Varela, Idania G Sánchez ; Guerrero, Orlando Valdés ; Braojo, Inés M Pérez ; Rubio, María Caridad

PURPOSE:

Dual HER2 blockade chemotherapy is the standard of care for localized HER2+ breast cancer (BC). However, despite the efficacy of neoadjuvant therapy, relapses occurring in around 10% of patients highlight the need to improve its clinical approach. Therefore, this study aimed to evaluate the effectiveness/safety of neoadjuvant therapy with subcutaneous (SC) trastuzumab- pertuzumab chemotherapy (real world) to extend the evidence, which comes mainly from clinical trials (selected population; intravenous [IV] trastuzumab).

MATERIALS AND METHODS:

A prospective, longitudinal, observational study in a Cuban hospital.

POPULATION:

women aged ≥18 years with histologically confirmed HER2+ early-stage BC (2017-2021) eligible for neoadjuvant treatment (IV pertuzumab, SC trastuzumab, taxane-based chemotherapy). The aim was to determine the pathological complete response (pCR) rate to this scheme, its safety, and the impact of patient's characteristics on the outcomes.

RESULTS:

Eighty-seven women were included: n=29 (DPT [docetaxel-IV pertuzumab- SC trastuzumab 600 mg; 4 cycles]); n=58 (ddAC-DPT [dose-dense anthracycline-based scheme+DPT]; 8 cycles). The median age was 57 years (range 30-83), ECOG 0: 97%. Time from diagnosis to treatment (median) was 28 days. The overall pCR rate was 62.1% (55.2%, DPT; 66.5%, ddAC-DPT; p =0.351); HR+, 47.7% vs. HR-, 76.7% (p=0.006). There were no statistically significant differences based on nodal status, stage, or Ki-67 levels. Overall, 94.2% of patients experienced ≥1 adverse event related to treatment, all of them grade 1-3 and more common with ddAC-DPT. The main cause of treatment delays (n=19; ddAC-DPT, 16; DPT, 3) was treatment-related toxicities.

CONCLUSION:

Neoadjuvant trastuzumab (SC) and pertuzumab plus chemotherapy for HER2+ early-stage BC showed benefits in a real-life setting, with an acceptable safety profile.

2020-03-01·ANNALS OF PHARMACOTHERAPY

Trastuzumab/Hyaluronidase-oysk: A New Option for Patients With HER2-Positive Breast Cancer

Review

作者: Duco, Marissa R. ; Reeves, David J. ; Murdock, Joshua L.

Objective::

To assess the use of subcutaneous trastuzumab/hyaluronidase-oysk (SQ trastuzumab) in comparison to intravenous (IV) trastuzumab.

Data Sources::

A comprehensive PubMed literature search was performed from August 2012 to August 2019 using search terms Herceptin Hylecta, trastuzumab, hyaluronidase, subcutaneous, preference, safety, efficacy, and cost.

Study Selection & Data Extraction::

English-language clinical trials focusing on SQ trastuzumab were evaluated.

Data Synthesis::

In phase III trials, adverse event (AE) rates ranged from 64% to 97.6% of patients receiving SQ trastuzumab in 3 studies compared to 94.6% of patients receiving IV trastuzumab. In the phase III trial comparing SQ trastuzumab to IV trastuzumab, six-year overall survival (OS) was 84% in both groups. In pharmacokinetic analyses, trough concentrations and AUC0-21 were slightly higher in patients receiving SQ trastuzumab and differences were larger at the extremes of body weight. Two pharmacoeconomic analyses reported cost-savings associated with a 52-week treatment cycle of trastuzumab of $2,090 USD and $4,600 USD.

Relevance to Patient Care and Clinical Practice::

Food and Drug Administration (FDA)-approved in February 2019, SQ trastuzumab, a monoclonal antibody that binds to human epidermal growth factor receptor 2 (HER2) protein in combination with hyaluronidase, offers an alternative dosage form for patients with breast tumors overexpressing HER2.

Conclusions::

SQ trastuzumab has a similar safety profile to IV trastuzumab. Although it may be slightly more cost-effective, its role in the treatment of HER2-overexpressing tumors requires further study in those at the extremes of body weight due to differences in drug exposure compared to IV trastuzumab.

2020-01-01·Current therapeutic research, clinical and experimental

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Recombinant Human Hyaluronidase PH20 Administered Intravenously in Healthy Volunteers

Article

作者: DeNoia, Emanuel P ; Souratha, Jennifer ; Zepeda, Monica ; Kang, David W ; Dychter, Samuel S ; Printz, Marie A ; Harrigan, Rena ; Sugarman, Barry J ; Maneval, Daniel C

BACKGROUND:

Recombinant human hyaluronidase PH20 (rHuPH20) is used in subcutaneous formulations (eg, RITUXAN HYCELA [rituximab and hyaluronidase human], HERCEPTIN HYLECTA [trastuzumab and hyaluronidase-oysk], PHESGO [pertuzumab/trastuzumab/hyaluronidase-zzxf], and Darzalex FASPRO [daratumumab and hyaluronidase-fihj]) to increase the dispersion and absorption of coadministered therapeutics. Although unlikely, subcutaneous products that include rHuPH20 could be mistaken for the intravenous formulation of the corresponding drugs (eg, RITUXAN [rituximab], HERCEPTIN [trastuzumab], and DARZALEX [daratumumab]). To understand the potential effects of inadvertent intravenous injection of rHuPH20, we investigated the safety profile, pharmacokinetics (PK), and pharmacodynamics (PD) of rHuPH20 administered intravenously.

OBJECTIVES:

This Phase I, open-label, single-center study in healthy volunteers was designed to assess the safety profile, tolerability, PK, and PD of rHuPH20 administered intravenously.

METHODS:

Healthy volunteers received 5 mL intravenous infusion of either 10,000 U (n = 12) or 30,000 U (n = 12) rHuPH20 over 5 minutes. Blood samples for PK and PD analysis were obtained at baseline and at various times after initiation of infusion. Adverse events and laboratory parameters were measured to assess the safety profile and tolerability of the intravenous infusion. The PK of rHuPH20 was assessed using both an enzymatic assay and a mass-based immunoassay, and plasma hyaluronan concentrations were measured as a PD marker using an HPLC-MS/MS disaccharide assay.

RESULTS:

All 24 volunteers (mean age = 36.5 years) completed the study, and no serious adverse events were reported in either treatment group. Overall, 2 adverse events (both Grade 1) were reported; catheter site pain in the 10,000 U group and hypotension in the 30,000 U group. Plasma concentrations of rHuPH20 increased during the 5-minute intravenous infusion (median t_max = 6 minutes from intravenous initiation) followed by a rapid plasma clearance (t_1/2 ∼10 minutes from intravenous initiation). Plasma hyaluronan concentrations increased with dose and time (t_max range = 45‒120 minutes from intravenous initiation) and returned to baseline within 1 week of administration. Changes in both PK and PD measurements appeared proportional to dose.

CONCLUSIONS:

The study demonstrated that intravenous administration of up to 30,000 U rHuPH20 was well tolerated, rapidly cleared from the plasma, and did not appear to be associated with any serious adverse effects at doses used in subcutaneous therapeutic products. (Curr Ther Res Clin Exp. 2020; 81).

项与曲妥珠单抗/透明质酸酶相关的新闻（医药）

2025-05-12

·BiG生物创新社

罗氏祭出「后手棋」

作者｜momo罗氏曾凭借肿瘤“三驾马车”叱咤市场，却在核心专利到期后遭遇生物类似药的猛烈冲击。面对收入断崖与竞争白热化，罗氏以眼科突破、肿瘤迭代和自免创新三线并进，试图在行业变局中重构护城河。 01 专利悬崖和市场挑战作为全球制药巨头，罗氏凭借1990年起对基因泰克的两次战略性收购，构建了以利妥昔单抗（Rituxan）、贝伐珠单抗（Avastin）和曲妥珠单抗（Herceptin）为核心的肿瘤药物矩阵。这三款被誉为“三驾马车”的重磅产品，曾贡献罗氏处方药收入的半壁江山，并在全球肿瘤治疗领域长期占据主导地位。其中，曲妥珠单抗作为HER2阳性乳腺癌治疗的基石药物，自1998年上市以来累计销售额超970亿瑞士法郎，年销售峰值突破70亿瑞士法郎，奠定了罗氏在靶向治疗领域的标杆地位。然而，随着核心产品专利相继到期（利妥昔单抗2018年、贝伐珠单抗与曲妥珠单抗2019年），生物类似药的冲击正迅速瓦解其市场壁垒。后续，三大产品的全球市场迅速被生物类似药分食。以利妥昔单抗为例，其全球销售额从2017年峰值74亿瑞士法郎锐减至2024年的11.16亿瑞士法郎（图1），中国市场更因复宏汉霖、信达生物等本土企业的仿制药竞争而持续承压。图1.利妥昔单抗（Rituxan）、贝伐珠单抗（Avastin）和曲妥珠单抗（Herceptin）为核心的肿瘤药物矩阵历年销售额为应对市场萎缩，罗氏于2025年将利妥昔单抗在中国的独家推广权移交百洋医药（图2），这一策略性外包旨在借助本土企业的渠道优势应对医保控费与集采压力，但亦折射出原研药在低价竞争中的被动局面。图2.罗氏将利妥昔单抗在中国的独家推广权移交百洋医药与此同时，曲妥珠单抗面临双重夹击。一方面，生物类似药以价格优势抢占基层市场；另一方面，HER2靶向治疗领域的技术迭代正在重构竞争格局，单纯依赖传统单抗的商业模式已显疲态。更为严峻的是，作为肿瘤免疫治疗领域的核心靶点，PD-(L)1抑制剂的市场竞争已进入白热化阶段（图3）。图3.中国已上市PD-(L)1产品罗氏旗下PD-L1抑制剂阿替利珠单抗（Tecentriq）虽在非小细胞肺癌、三阴性乳腺癌等适应症中占据重要地位，但其面临的生物类似药冲击即将显现。随着原研药专利到期临近（Tecentriq核心专利预计2030年后陆续到期），全球已有超过20家药企布局PD-(L)1生物类似药，直接威胁罗氏在中国这一全球第二大医药市场的份额。 02 巩固眼科拓宽肿瘤面对专利悬崖引发的市场冲击，罗氏以“巩固眼科优势”和“拓宽肿瘤版图”的双轨战略展开突围。其在眼科领域的突破性进展集中体现于双抗药物法瑞西单抗（Vabysmo）。该药物自2022年1月在美国获批以来，凭借“每4个月一次”的长周期给药方案和显著疗效，迅速抢占眼底病市场。至2024年，其上市第三年全球销售额已达44亿美元，同比增长68%，成为罗氏增长最快的单品之一（图4）。Vabysmo已覆盖新生血管性年龄相关性黄斑变性（nAMD）、糖尿病性黄斑水肿（DME）及视网膜静脉阻塞（RVO）三大适应症，且暂无直接竞品威胁。图4.Vabysmo正在成为罗氏的增长支柱2024年7月，FDA批准其6.0mg单剂量预充式注射器上市，进一步优化给药便捷性，为患者依从性与市场渗透率提升注入新动能。与此同时，在肿瘤领域，罗氏通过迭代升级与管线整合，逐步完成从传统单抗到创新疗法的过渡。帕妥珠单抗（Perjeta）、恩美曲妥珠单抗（Kadcyla）及阿替利珠单抗（Tecentriq）构成的新“三驾马车”，2024年合计贡献超105亿美元收入，成功接棒老牌产品（图5）。图5.罗氏肿瘤领域新三驾马车此外，罗氏在乳腺癌领域的深度布局进一步巩固其领导地位。针对PIK3CA突变导致的耐药难题，PI3K α 抑制剂Itovebi（inavolisib）于2024年10月获批，联合CDK4/6抑制剂与氟维司群治疗HR+/HER2-乳腺癌，临床数据显示其将患者中位无进展生存期（PFS）从7.3个月延长至15个月，疾病进展风险降低57%。更值得关注的是，针对乳腺癌的口服选择性雌激素受体降解剂Giredestrant的关键III期数据将于2025年公布；恩美曲妥珠单抗（Kadcyla）也在持续拓展早期乳腺癌辅助治疗适应症。为弥补研发短板，罗氏近两年密集开展肿瘤领域BD合作，38项交易中15项聚焦肿瘤创新疗法。2024年与锐格医药合作引进CDK抑制剂RGT-419B，补全CDK4/6抑制剂拼图；后续以15亿美元收购Poseida Therapeutics，更是强化了CAR-T细胞疗法在血液瘤与实体瘤的布局（图6）。图6.罗氏收购Poseida Therapeutics面对专利到期带来的收入危机，罗氏一手抓眼科新药快速变现，一手重构肿瘤产品生态，初步化解了专利悬崖引发的收入断层风险。 03 自免祭出后手棋与此同时，近年来，罗氏在自免领域悄然落子，以CD20单抗为矛、新兴靶点为盾，构建起抵御市场侵蚀的第二增长曲线。罗氏在CD20靶点的深耕印证了其战略韧性。初代产品利妥昔单抗（美罗华）虽在血液瘤领域创造72亿美元销售峰值，但专利到期后遭遇生物类似药围剿，2024年销售额已不足15亿美元。面对困局，罗氏通过适应症迁移实现价值重生。奥瑞利珠单抗（Ocrevus）转向多发性硬化症（MS）治疗，凭借半年一次的静脉输注方案，2024年以76.8亿美元销售额登顶自免领域Top5（表1），超越美罗华巅峰表现。表1.2024年全球自免药物销售额TOP 10这款第二代CD20单抗不仅将治疗领域从肿瘤转向自免，更通过剂型革新持续拓展生命周期，2024年9月FDA批准其皮下注射剂型Ocrevus Zunov，将年治疗次数缩减至2次、单次注射时间压缩至10分钟，患者依从性显著提升。（相关阅读：从自免到肿瘤，风卷残云的皮下制剂开发逻辑）第三代CD20单抗奥妥珠单抗（Gazyva）的布局更具深意。2024年9月，Gazyva在狼疮性肾炎的III期REGENCY试验中达到主要终点，标志着罗氏正式将CD20靶点战场延伸至系统性红斑狼疮（SLE）领域（图7）。图7.Gazyva在狼疮性肾炎的III期REGENCY试验中达到主要终点与此同时，其开发的CD3/CD19双抗RG6382和CD3/CD20双抗RG7828（Lunsumio）均正在开展针对系统性红斑狼疮的临床1期，罗氏正在构建覆盖B细胞通路的立体化治疗网络。此外，为突破CD20单抗的单一依赖，罗氏通过自主研发与并购加速新兴靶点布局。2023年71亿美元收购Telavant获得的抗TL1A抗体RG6631（RVT-3101），成为其攻占炎症性肠病（IBD）490亿美元市场的关键筹码。2025年启动的特应性皮炎与代谢相关脂肪性肝炎（MASH）试验，将进一步释放靶点价值。（相关阅读：TL1A靶点：两全其美的自免炎症通路放大器能否通过成药性考验？）2025年4月罗氏与Repertoire Immune Medicines达成协议，开发T细胞靶向免疫药物，进一步直指自免疾病根源性治疗（图8）。图8.罗氏与Repertoire Immune Medicines达成合作在神经免疫领域，口服BTK抑制剂Fenebrutinib的进展也尤为关键。2024年9月公布的II期FENopta研究显示，复发性多发性硬化症（RMS）患者接受治疗1年后疾病活动水平持续受控，残疾零进展。相较于现有注射疗法，其口服给药方式与中枢神经渗透优势，有望重塑治疗标准。纵观全局，罗氏以CD20为锚点、新兴靶点为支点的自免战略，展现出传统巨头转型的典型路径。若TL1A抗体和BTK抑制剂能如期兑现临床潜力，辅以CD20产品的持续迭代，其或将在2030年前构筑起500亿美元级自免防线，真正实现从“肿瘤依赖”到“双轮驱动”的跨越。结语罗氏这一系列“后手棋”，或将撬动医药行业的下一个黄金十年。参考资料[1]https://mp.weixin.qq.com/s/ApKIWyq49QH9Aw49-JkWrQ[2]https://mp.weixin.qq.com/s/DKId2oAq4UFowJEZ5pNcEw[3]https://assets.roche.com/f/176343/x/15cb053605/irp250130-a.pdf[4]https://www.roche.com/media/releases/med-cor-2024-11-26b[5]https://www.businesswire.com/news/home/20240925225486/en/Positive-Phase-III-Results-for-Genentechs-Gazyva-Show-Superiority-to-Standard-Therapy-Alone-in-People-With-Lupus-Nephritis[6]https://www.repertoire.com/about/press-releases/repertoire-immune-medicines-enters-into-collaboration-and-license-agreement-with-genentech-for-the-development-of-t-cell-targeted-therapies-for-an-autoimmune-disease共建Biomedical创新生态圈！如何加入BiG会员？

专利到期并购生物类似药

2025-05-05

·BiG生物创新社

K、O药领衔：开启单抗“分钟级”治疗时代

作者｜大道至简2025年3月默沙东宣布，帕博利珠单抗（可瑞达®，Keytruda®， K药）皮下注射版预计于今年10月获批。这是继去年年底，2024年12月百时美施贵宝的皮下型纳武利尤单抗（欧狄沃®，Opdivo Qvantig®，O药）后，全球第二款上市的PD-1单抗皮下注射剂。通过皮下给药的方式，单抗的单次治疗时间从数小时压缩至几分钟，患者治疗时间缩短90%以上。然而，皮下注射面临严苛的“不可能三角”：高浓度（保证药效）、低体积（≤2mL）、低刺激性（耐受性良好），三者难以同时满足。本文将从这一技术困局展开探讨，剖析行业突破路径，解读其面临的未来挑战。 01 技术瓶颈皮下单抗的“先天枷锁”静脉注射单抗的局限性长期困扰着医患双方。以PD-1抑制剂为例，单次静脉输注平均给药时间约0.5-2小时，患者每月需多次往返医院，输液过程中护士需全程监控输液反应，占用大量医疗资源。此外，与静脉注射相关的不良反应（如静脉炎、过敏反应）等，降低了患者依从性；部分患者需植入输液港，治疗体验差且易引发感染。因此，如何缩短治疗时间、优化资源分配，改善患者体验成为当务之急。1.1 大分子与皮下组织限制大分子单抗体积大，由于皮下细胞外基质（ECM）的3D网状结构，难以穿透皮肤组织，药物扩散受到限制。而且传统生物制剂在皮下的注射体积需控制在2ml以内，若超过这个范围会出现疼痛、鼓包等现象。1.2 剂量与体积的“生死博弈”单抗药物的治疗剂量通常在数百毫克级别，而皮下注射的体积在2mL以内。以纳武利尤单抗为例，常规静脉制剂的规格为10mg/mL，每两周用量为480mg，若直接改为皮下注射，要达到同样用量，2ml的皮下制剂的规格至少要提升至240mg/mL，是静脉给药的24倍。1.3 高浓度制剂的“陷阱”高浓度的制剂粘度高，注射时可能产生注射疼痛和组织损伤。此外，药物浓度过高会导致聚集、降低疗效，并引发免疫原性。 02 破局之道从配方优化到递送革命2.1 透明质酸酶——突破皮肤“防线”的钥匙重组人透明质酸酶（rHuPH20）成为突破皮下屏障的"破壁者"。它作为一种糖苷内切酶，可暂时降解透明质酸，通过局部皮下注射，改变皮下组织通透性，使药物能够快速扩散至血液循环系统，避免传统皮下注射的体积限制，提升注射容积上限，而且这种降解是暂时性的，通常在24-48小时内恢复，不影响皮下原有结构和功能。目前，这项Enhanze®给药技术的所有者——Halozyme公司，已将其授权给罗氏、强生、辉瑞等，产品开发涵盖肿瘤、罕见病、传染性疾病等多个领域。临床研究显示，罗氏使用该技术将皮下注射型曲妥珠单抗注射液（Herceptin Hylecta®）注射时间从1小时缩短至2至5分钟，药代动力学特征和静脉注射相似。强生的达雷妥尤单抗（Darzalex Faspro®）皮下注射剂2020年上市后，美国市场静脉注射向皮下制剂的转换率高达85%，而且近几年销售快速增长。根据强生最新2024年的财报，达雷妥尤单抗年销售额首次突破百亿美元，达到116.7亿美元。2.2 多抗复方制剂：剂量分摊的“巧思”在赫赛汀®皮下制剂成功的基础上，2020年罗氏又推出了多抗复方制剂——Phesgo®（赫捷康®），将帕妥珠单抗（Perjeta）与曲妥珠单抗（Herceptin）复配，通过共享rHuPH20载体，实现两种单抗同步皮下注射。一项关键临床III期研究（FeDerIca）数据显示，Phesgo®在疗效和安全性方面与静脉注射帕妥珠单抗和曲妥珠单抗相当。此外，由于缩短了给药时间，在患者偏好调查中，85%的患者更喜欢使用Phesgo®。2.3 抗体工程的“精准改造”罗氏靶向IL-6的萨特利珠单抗(satralizumab，Enspryng®，安适平)采用“再循环抗体技术”，通过改造Fc段增强与新生儿Fc受体（FcRn）结合，使抗体在细胞内循环利用，减少靶点介导的清除，提升血药浓度稳定性。该药于2020年首次上市，规格为1ml:120 mg，以皮下注射的方式给药，用于治疗视神经脊髓炎谱系疾病（NMOSD）。2021年11月，全球首个皮下注射的PD-L1“纳米抗体”——恩沃利单抗（Envafolimab，恩维达®）获得我国国家药品监督管理局（NMPA）批准上市，用于治疗不可切除或转移性的微卫星高度不稳定（MSI-H）或错配修复基因缺陷型（dMMR）的成人晚期实体瘤患者。这款由康宁杰瑞自主研发的PD-L1单抗，采用单域抗体（sdAb）融合人可结晶片段（Fc）的结构设计，具有分子量小、免疫原性低、毒性低的特点，而且组织穿透力和稳定性高；采用皮下注射方式，在30秒内完成给药，提高了患者依从性和便利性。2.4 递送设备创新：让注射更“无感”随着皮下预充注射笔、微针贴片、可穿戴设备等的出现，让患者可以在家中、社区，乃至其他任何环境中，灵活、便捷地自行治疗，进一步缩短注射时间、降低疼痛程度，实现无痛注射给药。2021年8月，信达生物的皮下注射产品阿达木单抗注射液（苏立信®）在中国获批上市，其为预充针剂型，采用BD Hypak™针头技术和组氨酸缓冲体系减轻注射疼痛，用于类风湿关节炎、强直性脊柱炎、银屑病等治疗。2022年，赛诺菲与Enable Injection合作，采用其enFuse可穿戴药物递送系统开发CD38抗体Isatuximab（Sarclisa®）的皮下注射剂型，以改善多发性骨髓瘤患者的治疗体验，目前尚处在临床研究早期阶段。接下来，我们对全球代表性的皮下单抗产品做一个简单梳理，如下表。（*：暂未批准，此为默沙东预计时间。）从表中可以看出，从罗氏Herceptin Hylecta®到近期默沙东Keytruda SC®，皮下单抗技术经历了从"依赖外源辅助"到"自主结构优化"演进，同时注射时间从分钟级迈入秒级时代，最终实现"浓度-体积-耐受性"三角平衡的技术跃迁。 03 未来挑战从技术到生态不容忽视的风险3.1 免疫原性：皮下注射的“隐形地雷”皮下单次和重复给药后可能增加产生抗药抗体（ADA）的风险，ADA可加速药物清除、降低血药浓度，影响治疗蛋白的药代动力学和药效学，从而削弱疗效。例如，阿达木单抗皮下给药后28%患者产生ADA，而曲妥珠单抗皮下制剂的ADA发生率（16%）也高于静脉制剂。3.2 稳定性：高浓度药物的难题高浓度单抗制剂最突出的挑战是在制造、运输和储存过程中的稳定性问题，可能导致聚集、降解和变性。因此，如何保持制剂的长期稳定性，并确保其在不同条件下的有效性是一个关键问题。3.3 成本与高定价的矛盾皮下注射单抗涉及复杂制剂工艺，与常规静脉制剂相比研发、生产成本高15%-20%。尽管可以通过纳入医保提升可及性，但皮下制剂的高定价在一定程度上会限制基层推广。写在最后从“静脉”到“皮下”，这场分秒必争的革命，我们看到皮下单抗的“不可能三角”正被逐一击破。当皮下注射技术将癌症治疗，从医院逐步向家庭与社区延伸，我们看到的不仅是给药方式的革新，更是医疗本质的回归——让技术服务于人。然而，医药开发者需始终牢记：任何技术创新都不能以牺牲安全性为代价。唯有在浓度、体积与耐受性间找到最佳平衡点，才能真正实现“患者获益最大化”的终极目标。参考资料1. Opdivo Qvantig®.BMS.2024年12月.2.ENHANZE®drug delivery technology.halozyme.com.3.Phesgo®.Roche.2020年6月.4.Enspryng®.Roche.2020年8月.5.恩沃利单抗（恩维达®）.康宁杰瑞.6.官网或其他公开资料.共建Biomedical创新生态圈！如何加入BiG会员？

申请上市上市批准

2025-03-14

·FiercePharma

Roche settles UPenn suit alleging patent infringement by Herceptin, 3 other breast cancer meds

A resolution between the University of Pennsylvania and Roche’s Genentech comes just days after a federal judge signed an order pausing the case. Some three years after the University of Pennsylvania claimed four of Roche’s breast cancer meds infringed its intellectual property, the parties have managed to resolve the dispute just weeks before a jury trial was set to start.Penn and Roche’s Genentech unit have settled the lawsuit Penn originally brought to a Delaware federal court in 2022, which accused the drugmaker of infringing a now-expired patent on methods of tumor treatment pioneered at the university’s Abramson Cancer Center.In turn, the case has been dismissed with prejudice, meaning neither party can retry their claims in court, according to a decision filed Friday in the U.S. District Court for the District of Delaware. The case was set to go before a jury March 31, Bloomberg Law reports. Details on the exact terms of the settlement agreement were not disclosed in Friday’s filing. The resolution comes just days after federal Judge Jennifer Hall signed an order pausing the case “pending performance of certain obligations under the settlement agreement reached by the parties,” according to a separate filing in the Delaware court.The stay on the case required that Penn and Genentech file a stipulation of dismissal or a joint update on their deliberations by March 24.Genentech confirmed with Fierce Pharma on Friday that "the parties have amicably resolved the dispute," though the company's spokesperson did not comment further on the outcome. Penn’s 2022 complaint against Genentech revolves around a patent, dubbed ‘558, that was originally granted to the school in December 2009.The ‘558 patent covers a method developed at Penn’s Perelman School of Medicine to treat patients with ErbB protein-mediated tumors by administering an antibody followed by radiation, according to the original lawsuit.According to the university’s lawyers, the treatment approach closely resembles that outlined in the FDA approvals for four of Roche’s anti-ErbB antibodies in breast cancer: intravenous Herceptin and the drug’s subcutaneous counterpart Herceptin Hylecta, plus Perjeta and Phesgo.By marketing that quartet of cancer meds, Roche infringed Penn’s ‘558 patent, the school’s lawyers argued in the 2022 lawsuit.Further, Penn’s legal team suggested the Genentech unit was “willfully blind to the fact that its acts were infringing” and contended that the company must have been aware of the school’s patent because Roche explicitly tried blocking foreign counterparts to the intellectual property at the European Patent Office in 2007, 2016 and 2019.In addition to seeking a ruling that Roche willfully infringed the ‘558 patent, Penn was originally pursuing an unspecified sum in damages as well as an ongoing licensing fee for Roche’s alleged use of its invention. The four breast cancer drugs at the center of the lawsuit continue to rake in sizable sales for Roche, though only Phesgo—which is the youngest of the quartet with its first approval in 2020—managed to grow in 2024 overall.For the entire year, Phesgo increased (PDF) sales 62% to 1.74 billion Swiss francs (nearly $2 billion), Roche reported in late January. Herceptin sales fell 11% to 1.38 billion Swiss francs ($1.5 billion) over the same period, while Perjeta’s 2024 sales dropped to 3.6 billion Swiss francs ($4 billion) versus roughly 3.8 billion Swiss francs in 2023.

专利侵权上市批准

100 项与曲妥珠单抗/透明质酸酶相关的药物交易

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10 条最早获批的记录,

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适应症	国家/地区	公司	日期
乳腺癌	美国	Halozyme Therapeutics, Inc.	2019-02-28
HER2阳性乳腺癌	美国	Genentech, Inc.	2019-02-28

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
早期乳腺癌	临床3期	美国	Hoffmann-La Roche, Inc.	2018-06-14
早期乳腺癌	临床3期	日本	Hoffmann-La Roche, Inc.	2018-06-14
早期乳腺癌	临床3期	阿根廷	Hoffmann-La Roche, Inc.	2018-06-14
早期乳腺癌	临床3期	比利时	Hoffmann-La Roche, Inc.	2018-06-14
早期乳腺癌	临床3期	巴西	Hoffmann-La Roche, Inc.	2018-06-14
早期乳腺癌	临床3期	加拿大	Hoffmann-La Roche, Inc.	2018-06-14
早期乳腺癌	临床3期	捷克	Hoffmann-La Roche, Inc.	2018-06-14
早期乳腺癌	临床3期	法国	Hoffmann-La Roche, Inc.	2018-06-14
早期乳腺癌	临床3期	德国	Hoffmann-La Roche, Inc.	2018-06-14
早期乳腺癌	临床3期	意大利	Hoffmann-La Roche, Inc.	2018-06-14

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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


NCT03493854 (FeDeriCa, CTgov)	临床3期	HER2阳性乳腺癌 \| 早期乳腺癌	500	Post-operative Radiotherapy+Trastuzumab SC+Trastuzumab IV+Cyclophosphamide+Doxorubicin+Paclitaxel+Pertuzumab IV+Docetaxel	糧憲顧壓積範膚鏇顧繭(衊餘憲遞簾鑰襯鑰觸鑰) = 壓顧簾簾觸簾憲繭鹹繭鹹憲構簾積膚窪製齋鏇 (鬱壓憲醖繭艱製觸築蓋, 34.1) 更多	-	2020-06-25
NCT00127933 (CTgov)	临床4期	HER2阳性乳腺癌 \| 浸润性乳腺癌	157	taxotere+capecitabine [Xeloda] (HER2-Neu Negative)	餘顧顧糧願鬱鏇觸遞齋 = 構齋膚選鹽簾築衊簾獵選構獵範鏇觸齋鹹憲願 (繭廠鏇蓋夢憲繭鹽築構, 蓋築願餘蓋齋遞餘夢鑰 ~ 鬱餘願繭觸膚鏇艱築齋) 更多	-	2011-08-10
NCT00127933 (CTgov)	临床4期	HER2阳性乳腺癌 \| 浸润性乳腺癌	157	Herceptin+HER2-neu+taxotere+capecitabine [Xeloda] (HER2-Neu Positive)	餘顧顧糧願鬱鏇觸遞齋 = 範築淵膚願鹹鏇夢艱製選構獵範鏇觸齋鹹憲願 (繭廠鏇蓋夢憲繭鹽築構, 齋鹽鑰製衊構艱廠構築 ~ 簾獵餘範繭齋觸襯廠獵) 更多	-	2011-08-10