A Randomized, Open-Label, Controlled Phase 3 Study of Comparing Daratumumab, Lenalidomide and Dexamethasone Induction Followed by Linvoseltamab Versus Continued Daratumumab, Lenalidomide, and Dexamethasone in Newly Diagnosed Transplant Ineligible Multiple Myeloma Patients

This study is researching an experimental drug called linvoseltamab. The study is focused on participants with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplantation (transplant-ineligible).
The main purpose of this study is to compare the effect and safety of linvoseltamab with the effect and safety of the standard treatment.

开始日期2025-09-01

申办/合作机构

European Myeloma Network

[+1]

NCT06948084

/ Not yet recruiting临床2期IIT

A Randomized Phase II Trial for High-Risk Multiple Myeloma That is Refractory or in First Relapse With Daratumumab, Teclistamab (DT) Versus Daratumumab, Pomalidomide, Dexamethasone (DPd) or Daratumumab, Carfilzomib, Dexamethasone (DKd)

This phase II trial compares the effect of the combination of daratumumab-hyaluronidase (daratumumab) and teclistamab to the usual treatment of daratumumab, pomalidomide, dexamethasone or daratumumab, carfilzomib and dexamethasone in treating patients with multiple myeloma that has not responded to previous treatment (refractory) or that has come back after a period of improvement (relapsed). Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Teclistamab is a bispecific antibody that can bind to two different antigens at the same time. Teclistamab binds to B-cell maturation antigen, a protein found on some B-cells and myeloma cells, and CD3 on T-cells (a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Pomalidomide is in a class of medications called immunomodulatory agents. It works by helping the immune system kill cancer cells and by helping the bone marrow to produce normal blood cells. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Carfilzomib, a type of proteasome inhibitor, blocks the action of enzymes called proteasomes, which may help keep cancer cells from growing and may kill them. Giving daratumumab and teclistamab may be more effective than the usual treatment of daratumumab, pomalidomide, dexamethasone or daratumumab, carfilzomib and dexamethasone in reducing myeloma cells to undetectable levels in patients with relapsed or refractory multiple myeloma.

开始日期2025-07-18

申办/合作机构

National Cancer Institute

NCT06046287

/ Recruiting临床2期IIT

Phase IIa Study to Evaluate Daratumumab for Polyneuropathy Associated With MGUS

The goal of this clinical trial is to learn about daratumumab and hyaluronidase-fihj in patients with monoclonal gammopathy of undetermined significant (MGUS) who have been diagnosed with peripheral neuropathy suspected to be cause by paraproteinemia. The main question[s] it aims to answer are:
• how well does this medication help improve MGUS associated peripheral neuropathy
Participants will be asked be asked to get some testing done prior to starting the trial in order for us to assess your nerve damage or peripheral neuropathy. This will include blood tests, a complete neurologic examination, surveys and tests called electromyogram and nerve conduction studies. Participants that qualify for the trial will take DARZALEX FASPRO® once a week for two months, followed by every other week from months 3 to month 6.

开始日期2025-07-01

申办/合作机构

Georgetown University

[+1]

100 项与达雷妥尤单抗相关的临床结果

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100 项与达雷妥尤单抗相关的转化医学

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100 项与达雷妥尤单抗相关的专利（医药）

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2,040

项与达雷妥尤单抗相关的文献（医药）

2025-12-31·ANNALS OF MEDICINE

Serum free light chain level-based and non-fixed cycle daratumumab treatment strategy for patients with light chain amyloidosis

Article

作者: Huang, Xianghua ; Guo, Jinzhou ; Chen, Wencui ; Li, Zhen ; Zhao, Liang ; Ren, Guisheng

BACKGROUND:

In recent years, daratumumab (DARA) has gained widespread use in the treatment of systemic light chain (AL) amyloidosis. In this study, we assessed the efficacy and safety of a DARA treatment strategy based on serum free light chain (sFLC) levels and non-fixed cycles.

METHODS:

The study included 123 patients with Al amyloidosis who received DARA at our center between July 2020 and September 2023. All patients received the standard DARA treatment (16 mg/kg weekly for four weeks) during the first course. Subsequent treatments were adjusted based on sFLC levels and the physician's judgment.

RESULTS:

The results demonstrated an impressive overall hematologic response rate (ORR) of 94.3%, with a hematologic very good partial response (VGPR) and complete response (CR) rate of 84.5%. Median time to best hematologic response was 1 months. Cardiac and renal response rates were 39.3% and 60.3%, respectively. Thirty patients experienced grade 1/2 infusion-related reactions after the first infusion. The rate of grade 3/4 adverse events was 21%. The most common adverse events of grade 3 or 4 were pulmonary infection (6.5%), neutropenia and lymphocytopenia (5.7%), elevated transaminases (1.6%), acute kidney injury (1.6%). After a median follow-up of 13 months (range 1-38), The 1-year OS and PFS estimates were 96.5% and 84.4%, respectively.

CONCLUSION:

These findings indicate that the sFLC levels based and non-fixed cycle DARA strategy is an efficacious and safe treatment strategy in both newly diagnosed and relapsed/refractory AL amyloidosis.

2025-12-31·ANNALS OF MEDICINE

Clinical outcome of ≥2% circulating tumor cells in newly diagnosed multiple myeloma: insights from a multicenter study

Article

作者: Liang, Dong ; Wang, Hua ; Xia, Zhongjun ; Feng, Yuan ; Yan, Yurong ; Jin, Fengyan ; Chen, Xiaoqin ; Nie, Xiaomiao ; Zeng, Min ; Bu, Yuying ; Bai, Shenrui ; Liang, Yang ; Wang, Qiaoli ; Xu, Weiling ; Feng, Demei

PURPOSE:

Previous studies have shown that ≥2% circulating tumor cells (CTCs) in multiple myeloma are associated with a prognosis similar to primary plasma cell leukemia. This study aims to examine this ultra-high-risk patient subset and evaluate their clinical outcomes in a real-world clinical setting.

METHODS:

We included 1,056 newly diagnosed multiple myeloma patients treated with novel agents. CTCs levels were determined via morphological assessment on peripheral blood smears, using a 2% cutoff to stratify patients into <2% and ≥2% CTCs groups. We then evaluated clinical outcomes across these groups.

RESULTS:

Patients with ≥2% CTCs constitute an ultra-high-risk subgroup, with outcomes resembling those of primary plasma cell leukemia. Survival outcomes improved for patients receiving daratumumab-based quadruplet therapy. Single autologous stem cell transplantation (ASCT) partially improved outcomes for patients with ≥2% CTCs. Achieving complete remission (CR) after induction treatment did not confer a better prognosis for this population. Furthermore, one high-risk cytogenetic abnormality (HRA) worsened outcomes in the <2% CTC group, while ≥2 HRA were associated with poorer outcomes in the ≥2% CTC group. Concurrent 1q21+ and other HRA further conferred a worse prognosis. In de novo extramedullary extraosseous (EME) multiple myeloma, defined as patients presenting with soft tissue or visceral plasmacytomas not connected to bone at initial diagnosis, ≥2% CTCs remained a strong predictor of poor prognosis.

CONCLUSION:

Our study suggests that patients with ≥2% CTCs represent a distinct ultra-high-risk subgroup in multiple myeloma and warrant separate consideration. VRD, IRD, DVRD, and DRD were reliable choices as frontline therapies for patients with <2% CTCs. Daratumumab-based quadruplet therapy may be a promising option for patients with ≥2% CTCs. Further research should continue to explore this specific aspect in greater depth.

2025-12-31·DRUG DELIVERY

Evaluating nurse preferences for a novel on-body delivery system vs. manual syringes for large-volume subcutaneous drug administration: a survey study

Article

作者: Gorski, Lisa A. ; Curry, Nicole ; Sterlin, Valentina ; Miles, Ashley ; Desai, Mehul ; Faiman, Beth

While nurses report challenges with the manual administration of large-volume subcutaneous drugs, these challenges and potential solutions are not captured in the literature. In this cross-sectional study, 45 nurses with experience administering large-volume subcutaneous biologics completed an 18-item survey about preferences for syringes vs. on-body delivery systems. 100% responded that an on-body delivery system seemed easy to learn and use and preferable to syringes. In a drug delivery scenario including comprehensive administration details and assuming equivalent safety and efficacy, 97.78% preferred the on-body delivery system to a daratumumab/hyaluronidase syringe. In the total sample, this preference was primarily attributed to (1) reduced nurse effort due to hands-free delivery, (2) decreased patient pain due to a thinner needle, (3) elimination of needlestick injuries due to a hidden needle, and (4) increased clinic efficiency due to hands-free delivery. 95.56% felt that the on-body delivery system would improve clinic throughput better than syringes. Nurses reported that an on-body delivery system would be easy to learn and use and would improve clinic efficiency and safety. They underscored the importance of decreasing nurse physical burden, needlestick injuries, and patient needle phobia. Contrary to the assumption that speed is paramount, nurses prioritized reducing effort, enhancing administration safety, and improving patient comfort over injection speed.

983

项与达雷妥尤单抗相关的新闻（医药）

2025-05-27

·CPHI制药在线

新一波专利悬崖面前，制药巨头安危分析

关注并星标CPHI制药在线制药领域是一个花无百日红的场所，不仅是因为“江山代有才人出”，也因为“风流总被雨打风吹去”。一款曾经“一览众山小”的重磅药物，在专利到期之后面对的通常会是“故国不堪回首月明中”的落寞。药品专利，这个起初旨在维护制药公司利益的保护伞，在逐渐走向专利悬崖的后期，却成为这些公司如芒在背的威胁。专利悬崖对大型制药公司，尤其是对那些依赖几款超级重磅炸弹药物的制药公司构成非常严重的威胁。当这些药物的专利到期后，仿制药制造商迅速进入市场，推出价格远低于原研药的替代品。这将直接导致原研药销售额的骤降，并削弱了这些开发商的盈利能力。由于超级重磅炸弹药物通常占公司总收入的相当大部分，一旦失去专利保护，公司可能难以在短期内通过新药研发或收购来弥补收入缺口。因此专利悬崖不仅威胁到公司的财务稳定，还可能影响其研发投入和市场竞争力。放眼大时代，2026-2030 年，生物制药行业将进入动荡时期，众多超重磅药物将在这一时期失去美国市场独占权。几乎所有大型制药公司都将或多或少受到头顶的这把专利到期达摩克利斯之剑的影响，但受威胁程度疾徐不一。诺和诺德、赛诺菲、吉利德、礼来和拜耳可能是2030年前“受灾”程度最小的五家制药巨头（表1，图1-2）。根据 Evaluate Pharma 的数据和Scrip的分析，预计从2026年至2030年，这五家制药商因专利到期遭受的损失将不超过各自2025年美国市场预测收入的15% 。在诺和等五家制药公司“事大如天醉亦休”地置身其外的同时，感受“日长似岁”般煎熬的制药巨头将面临渡劫。这些公司可能会因 2026 年至 2030 年美国专利到期药物而损失50% 以上的收入，其中葛兰素史克、百时美施贵宝和默沙东将面临最大危局。葛兰素史克的 Tivicay（多替拉韦）和 Dovato（拉米夫定）、百时美施贵宝的 Eliquis（阿哌沙班）和 Opdivo（纳武利尤单抗）以及默沙东的药王 Keytruda（帕博利珠单抗）等超级重磅药物可能将在这个时间段面临仿制药或生物类似药的竞争。表1. 全球大型制药公司2026-2030年受专利悬崖影响数据（数据来源：Evaluate Pharma）图1. 2025年预计美国市场收入中遭受2026-2030年间市场独占权丧失威胁的比例。（数据来源：Evaluate Pharma)图2. 大型制药公司2025年预计收入中面临2026-2030年间市场独占权丧失威胁的绝对数额。（数据来源：Evaluate Pharma）A.安全榜1.诺和诺德（2% 风险）诺和诺德的支柱性产品无疑是其Semaglutide产品组合，尤其是Ozempic和Wegovy。虽然诺和诺德将在GLP-1市场遭遇礼来和众多后来者的严峻挑战，以及Medicare价格谈判的潜在影响，但从专利悬崖的角度来看，诺和面临的压力要比默沙东小得多。Semaglutide在美国市场的核心专利保护预计将延续到2031年，这将赋予诺和诺德宝贵的开发新产品的黄金时间，在享受semaglutide巨大红利的同时，将利润投入到新一代产品的开发中，例如GLP-1/胰淀素类似物联合疗法CagriSema。2.赛诺菲（9% 风险）赛诺菲CEO Paul Hudson在今年1月召开的摩根大通医疗保健大会的演讲中就曾信誓旦旦地表态，“就独占权丧失而言，赛诺菲是业内最低的”。赛诺菲的当家花魁Dupixent (dupilumab) 仍处在生命周期的黄金时代，被批准用于从牛皮癣到哮喘等多种炎症疾病，最近还获得了慢性阻塞性肺病 (COPD)的批准，进一步夯实了这款超重磅药物的盈利能力。Dupixent 的专利保护期将持续到 2030 年代初。其活性成分专利将于 2031 年到期，其他专利有效时间则更长。Evaluate Pharma 的数据显示，赛诺菲预计的2025 年美国收入中只有 9% 会因 2026 年至 2030 年期间的市场独占丧失而损失，但这些损失多数来自“帐中副将”，例如乙型血友病药物Alprolix（重组凝血因子IX-Fc融合蛋白）和慢性移植物抗宿主病药物Rezurock（belumosudil），预计它们将分别在 2028 年和 2029 年失去独占权。3.吉利德（9%风险）吉利德追求的目标之一是在其核心 HIV 业务之外成功实现更多多元化，这个志向是建立在其HIV 业务一直在实现增长的基础之上的。吉利德最畅销的联合疗法的专利目前还一眼望不到底，2033 年底之前可保无虞。Biktarvy 在 2024 年的销售额为 134 亿美元，占吉利德总收入的将近48%。吉利德表示，在Biktarvy收入曲线进入下行阶段之前，他们将有能力推出新一代长效HIV药物。吉利德2025 年美国收入中只有9%将遭受到2026-2030年市场独占权丧失的影响，包括2027 年到期的CD19 靶向CAR-T疗法，而考虑到 CAR-T 疗法制造的复杂性，Tecartus未必在市场独占期到来之后立即面临生物类似药的竞争。4.拜耳（风险 13%）处在多事之秋的拜耳，其重磅产品血液稀释剂 Xarelto（rivaroxaban）市场独占期在2024年4月已经到来，令拜耳更加感受到压力重重。但遭受亏损的拜耳有望在2027年实现业务增长。拜耳CEO Bill Anderson 认为，用于治疗与 2 型糖尿病相关的慢性肾病的盐皮质激素受体拮抗剂 Kerendia（finerenone）和前列腺癌药物 Nubeqa（darolutamide）等新药将有助于推动拜耳回春。此外，BridgeBio 的 acoramidis 在欧洲将由拜耳负责商业化（欧洲商品名Beyonttra），针对转甲状腺素蛋白淀粉样心肌病 (ATTR-CM)。拜耳的elinzanetant针对更年期相关的中度至重度血管舒缩症状的申请正在等待FDA的监管审批。5.礼来（风险 15%）礼来的旗舰产品Mounjaro和Zepbound相对于其直接竞争对手，诺和诺德的Ozempic和Wegovy更加年轻。其活性成分tirzepatide的专利至少要到2036年才到期，这位礼来长期盈利提供了关键保障。礼来公司在 2026-2030 年期间也将面临一些畅销药物的专利损失，包括预计在 2027 年失去市场独占的糖尿病重磅药物 Trulicity（dulaglutide），其2024 年为礼来创造了 52.5 亿美元的收入；以及在 2030 年失去专利保护的牛皮癣药物 Taltz（ixekizumab），其2024 年销售额达到36 亿美元。B.风险榜1.默沙东（78%）Keytruda，默沙东的这款支柱产品免疫检查点抑制剂肿瘤学产品2024年销售额高达295亿美元，而默沙东全年销售额为642亿美元。也就是说，Keytruda以一己之力贡献了默沙东全部销售额的46%，这是一个非常卓越的成就，但同样也包藏祸机，因为Keytruda在美国的关键专利将在2028年到期，Keytruda专利悬崖危机成为默沙东目前的头号挑战。随着 Keytruda、Sitagliptin/Metformin和 Letermovir 的专利即将到期，默沙东未来五年将面临严峻挑战。另一个主要收入来源 HPV 疫苗 Gardasil 9 因中国市场饱和而表现不佳，导致默沙东于 2024 年 2 月暂停发货以清理库存，在 2025 年可能会恢复增长。为了保持增长，默沙东抗体药物偶联物 (ADC) 方面投入了大量资金，包括与科伦生物科技和第一三共的合作。2.GSK（62%）葛兰素史克的dolutegravir一直是其HIV 药物组合的主要产品，是葛兰素史克四个最畅销的 HIV 品牌 Tivicay（13.5亿英镑）、Triumeq（13.3亿英镑）、Juluca（6.85亿英镑）和 Dovato （22.4亿英镑）中的成分。但其关键专利可能将于2027年到期。3.BMS (55%)百时美施贵宝的Eliquis (Apixaban) 和 Opdivo 正面临专利悬崖危机，2024 年这两款药物的营收为 234 亿美元，占公司总营收的近一半。Eliquis面临即将到来的仿制药竞争，Eliquis是BMS与辉瑞共同商业化的产品，是一种用于预防成人血栓的小分子药物，2012年获得FDA批准，2023年实现全球122亿美元的销售额。其专利已于2022年到期，但得益于补充保护证书（Supplementary Protection Certificate）的荫护，其保护期已延长到2026年。实际上，Eliquis仿制药已经获得了FDA的临时批准，但BMS与仿制药商已经达成和解，仿制药不会在2027年之前上市。作为回应，BMS 实施了积极的成本削减措施，包括 2024 年 4 月的 15 亿美元成本削减计划和 2025 年 2 月的额外 20 亿美元削减计划，包含削减产品线和裁员。BMS 还将重点转向神经科学，以 140 亿美元收购了 Karuna Therapeutics，并投资了精神分裂症药物 Cobenfy。C.2025-2031年间失去市场独占权的重要药物2025年• Entresto (sacubitril/valsartan，诺华，2015年获批，2024年全球销售额：78.2亿美元，下同)• Farxiga (Dapagliflozin，诺华，2014年获批，2型糖尿病，38.4亿美元)• Prolia (denosumab，安进，2010年获批，骨质疏松症，43.7亿美元)• Xgeva (denosumab，安进，2010年获批，肿瘤，22.3亿美元) 2026年• Eliquis (apixaban，BMS/辉瑞，2012年获批，血栓，122亿美元)• Revlimid (lenalidomide，BMS，2005年获批，骨髓增生异常综合征、多发性骨髓瘤、淋巴瘤、滤泡性淋巴瘤等，57.7亿美元) 2027年• Trulicity (dulaglutide，礼来，2014年获批，2型糖尿病，52.5亿美元)• Ocrevus (ocrelizumab ，罗氏，2017年获批，多发性硬化症，67亿美元)• Ibrance (Palbociclib，辉瑞，2015年获批，乳腺癌，43.7亿美元)• Xtandi (enzalutamide，安斯泰来/辉瑞，2012年获批，前列腺癌，63亿美元)• Imbruvica (ibrutinib，艾伯维/强生，2013年获批，慢性淋巴细胞白血病等，49亿美元)• Dolutegravir药物组合 (GSK，2013年获批，HIV，56亿英镑) 2028年• Keytruda (pembrolizumab，默沙东，2014年获批，肿瘤，295亿美元)• Opdivo (nivolumab，BMS，2014年获批，肿瘤，93亿美元)• Gardasil 9 (human papillomavirus 9-valent vaccine ，2014年获批，默沙东，86亿美元) 2029年• Darzalex (daratumumab，强生/Genmab，2015年获批，多发性骨髓瘤，117亿美元)• Cosentyx (secukinumab，诺华，2015年获批，斑块性银屑病等，61.4亿美元)• Enbrel (etanercept，安进，1998年获批，类风湿性关节炎等，33.2亿美元) 2031年• Dupixent (dupilumab，赛诺菲/再生元，2017年获批，特应性皮炎、哮喘、慢性阻塞性肺病等，131亿欧元)Ref. 1、Merck Announces Fourth-Quarter and Full-Year 2024 Financial Results. Merck Press Release. 04. 02. 2025. 2、Merrill, J. et al. Five Companies Heading Toward 2030 With Wind At Their Back. Scrip. 26. 02. 2025. 3、2024 Financial report of various pharmaceuticals. 4、Pharma patent cliff. LinkedIn: Joanna-sadowska-phdEND【企业推荐】智药研习社直播预告来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

专利到期并购生物类似药

2025-05-26

·微信

强生顶住了压力

氨基观察/武月药王如何养成？影响的要素太多太多。药企需要有足够的研发实力，对于疾病治疗的理解绝对超前......甚至，还需要具备“力排众议”的能力。新晋百亿美金药王达雷妥尤单抗，就在上演这一幕。5月20日，强生旗下达雷妥尤单抗，获得FDA肿瘤药物顾问委员会（ODAC）6:2的投票支持，用于高危冒烟型多发性骨髓瘤（HR-SMM）的适应症。虽然能否获批还需FDA拍板，但这仍然意味着，其有可能进一步改写多发性骨髓瘤早治领域的游戏规则，治疗关口前移至无症状的癌前阶段，将“观察等待”的高危SMM患者纳入主动干预范畴。毕竟，获得ODAC认可，距离成功只差临门一脚。但事实上，该适应症的研发，并不是一帆风顺，而是争议不断，最核心的焦点是：早期干预是否必要？延缓进展是否等于临床获益？FDA专家委员会的三重质疑，折射出肿瘤早治领域的共性难题。好在结果不错，尽管争议未止且数据存疑，但是强生还是说服了多数专家。“力排众议”，本质也是在治疗理念不断重构的变革中，药企突破传统诊疗范式的战略魄力。达雷妥尤单抗的突围历程或许也在告诉市场，这将是药企不得不具备的能力。01争议未止，强生执意“拓荒”多发性骨髓瘤的癌前状态，始终是血液肿瘤领域的一个争议焦点。在病情发展到MM之前，很多MM患者最初的表现就是意义不明的单克隆丙种球蛋白血症（MUGS），这也是MM的第一个阶段。之后，克隆性浆细胞在骨髓中不断增殖，逐渐进展为MM的第二个阶段——阴燃多发性骨髓瘤（或称为冒烟型多发性骨髓瘤，SMM）。这时疾病还处于恶变的边缘，患者通常也没有明显的症状，但骨髓里已经有了大量的克隆性浆细胞。随着克隆性浆细胞进一步完成癌变，成为恶性浆细胞，病情也进展为真正的多发性骨髓瘤。大多数MM患者在发病前，都会经历很长的MUGS和SMM阶段，MUGS患者和SMM患者每年进展为MM的风险大约分别为1%~2%和10%。SMM作为MM的无症状前驱阶段，虽无CRAB症状（高钙血症、肾功能不全等），但高危患者3年内进展为活动性MM的风险超过50%。然而，在这个阶段，并没有有效的手段来阻止病情的进展，能做的只有观察等待，在发展为MM，出现临床症状后再加以治疗。争议的核心也在于此，即“治疗必要性”。反对者认为，SMM肿瘤负荷低，部分患者可能终生无需治疗，过早干预可能导致过度医疗；支持者则指出，高危SMM的生物学行为已接近活动性MM，早期根除恶性克隆有望实现“治愈”。这种分歧也体现在临床实践中：美国国家综合癌症网络（NCCN）指南仅建议高危患者参与临床试验，而欧盟部分国家已尝试有限度的早期干预。强生选择在争议中“拓荒”。2024年ASH年会公布的Ⅲ期Aquila试验显示，与单纯观察在高危SMM患者相比，达雷妥尤单抗单药治疗高危SMM患者，将疾病进展风险降低51%，且早期趋势显示可能延长患者总生存期。具体来说，达雷妥尤单抗治疗组总缓解率（ORR）达到了 63.4% ，而主动监测组几乎没有缓解（对照组ORR约为1%-2%），其中 8.8% 的患者达到了完全缓解（CR）或更好缓解，对照组则为0%；无进展生存（PFS）方面，随访中位时间约65个月，达雷妥尤单抗治疗组为 63.1%，主动监测组为 40.8%；五年总生存率（OS）方面，达雷妥尤单抗治疗组为93% ，主动监测组为86.9%。安全性方面，达雷妥尤单抗组治疗相关不良事件发生率更高，治疗中出现的3级或4级不良事件（TEAE）为40.4%，对照组为30.1%。基于此，强生于2024年向FDA和EMA提交申请，寻求批准达雷妥尤皮下制剂用于HR-SMM。若成功，这将是首个针对癌前状态的MM疗法。02FDA三问疗效价值尽管强生认为，高危 SMM患者可以从主动治疗中受益，而仅仅监测是一种不可取的选择。但也面临着部分FDA专家的质疑。美国国家癌症研究所的医学博士Ravi Madan投出了反对票，其认为，这是一个更广泛的问题，贯穿整个肿瘤学领域。“我们每天都在获得更好的技术。我们有更多机会更早地治疗。我再想一遍，我们必须真正退后一步，问问自己，仅仅因为我们可以更早地治疗，我们应该这样做吗？”在此次专家审评会上，质疑主要围绕以下三点。其一，入组人群是否真正高危？FDA 指出，Aquila试验中仅41%患者符合现行高危标准（如IMWG 20/2/20模型），也就是说招募了超过一半不符合当前高风险标准的患者。对此，强生表示，每个标准都会错过一些将在前两三年内进展的患者，制定的标准越严格，就会错过更多的人。因此，该试验采用更宽泛的入组标准，以覆盖不同高危分层患者，对照组50%患者在3年内进展，提示整体人群风险仍较高，亚组分析显示各人群获益一致。其二，延缓进展的临床意义何在？FDA认为，单纯推迟进展时间未必能够转化为生存获益，需结合二线治疗PFS和OS数据。并且，FDA不相信两个试验组在5年时总生存率相差6个百分点，Aquila试验没有足够的把握度来显示显著的生存获益。对此，强生反驳称，对于一种惰性肿瘤，迄今为止显示的生存率改善并没有太多意义，但这种早期治疗对患者的意义相当深远。其三，早期治疗会否影响后续疗效？FDA担忧，早期使用CD38单抗可能诱导耐药，以及该药的安全性问题，会对后续治疗造成潜在影响。强生则强调，Aquila试验中，进展后接受含达雷妥尤单抗治疗的患者仍显示响应，且皮下制剂安全性良好（3/4级不良事件发生率40.4%，停药率仅5.7%）。此外，MM治疗已进入多药联合时代，CD38单抗耐药并非不可克服。当然，尽管存在种种质疑，最终6:2的投票结果，也表明了多数专家认可“高风险人群的获益大于风险”。毕竟，当一种药物能将高危SMM的5年进展风险砍半，且毒性相对可控时，拒绝治疗可能意味着错失良机。03重构传统范式的魄力达雷妥尤单抗的“更进一步”，既是科学突破，也是商业谋略。强生的意图十分清晰，凭借达雷妥尤单抗在MM全病程已经建立的优势，进一步“吞噬”癌前市场，构建从SMM到复发难治MM的治疗闭环。这种全周期覆盖模式，不仅巩固其市场地位，更可能重塑临床实践，将MM防治推向更早阶段。换句话说，若达雷妥尤单抗最终获批，其影响可能不止于单一适应症。一方面，SMM治疗可以从“空白”走向“标准”。当前NCCN指南仅推荐高危患者入组临床试验，而达雷妥尤单抗可能成为首个标准疗法，推动早期干预理念普及。这可能会为强生开辟另一片新战场，并巩固其“全病程霸主”地位。达雷妥尤单抗已覆盖MM一线诱导、维持治疗及2-5线复发治疗，若再纳入SMM，将形成“癌前-一线-复发”的全周期覆盖。后来者则更需要在疗效或给药方式上实现新的突破，才可能撼动其优势。另一方面，这可能会一进步引发早治策略的连锁反应。强生的开发和监管经历，虽然向我们展示了药企在进行早期癌症临床试验时面临的更大困难，但也会激励药企探索肺癌、乳腺癌等癌种的早治药物，推动肿瘤治疗加速从“被动应战”转向“主动出击”的新阶段。这对于患者来说，无异于生存期的质的飞跃。当然，我们也需警惕过度医疗风险。当药企们不断推前治疗关口，医学界必须回答，到底是在治愈疾病，还是在制造需求？达雷妥尤单抗的答案或许即将揭晓，但整个行业的思考，才刚刚开始。往期推荐1医健企业前沿动态2医健行业BD/出海/投融资洞察___*声明：本稿件为转载，仅用于分享，不代表本公众号立场，如涉及版权等问题，请尽快联系我们，我们将第一时间更正或删除，谢谢！

2025-05-23

·Firstwordpharma

Blenrep comeback continues with EU recommendation, plus a thumbs up for Itovebi

GSK's bid to bring back multiple myeloma therapy Blenrep (belantamab mafodotin) got a major boost on Friday when the antibody-drug conjugate (ADC) received a positive opinion from the EU's drug advisory panel. Also receiving a positive vote from the European Medicine Agency's Committee for Medicinal Products for Human Use (CHMP) was Roche's breast cancer drug Itovebi (inavolisib). Survival data for the PI3K inhibitor was recently spotlighted in an abstract released ahead of the American Society of Clinical Oncology (ASCO) meeting (see – ASCO25 abstract roundup: Roche's Itovebi cuts risk of death).Autolus' CAR-T cell therapy Aucatzyl (obecabtagene autoleucel) also received a thumbs up from CHMP, as well as mirdametinib, a MEK inhibitor recently acquired by Merck KGaA in its $3.9-billion takeout of SpringWorks Therapeutics. Blenrep is backBlenrep was withdrawn from global markets in 2022 following disappointing results from a confirmatory trial, but after positive readouts from two pivotal Phase III trials — DREAMM-7 and DREAMM-8 — GSK has been working to bring the BCMA-targeted ADC back. Specifically, CHMP recommended Blenrep to treat relapsed or refractory multiple myeloma in combination with bortezomib and dexamethasone (BVd) for adults who have received at least one prior therapy; and in combination with Bristol Myers Squibb's Pomalyst (pomalidomide) plus dexamethasone for patients who have received at least one prior treatment, including BMS's Revlimid (lenalidomide). In DREAMM-7, Blenrep plus BVd achieved a progression-free survival (PFS) of 36.6 months, versus 13.4 months for the comparator regimen of Johnson & Johnson's Darzalex (daratumumab) plus BVd.DREAMM-8 compared Blenrep to bortezomib, both in combination with Pomalyst and dexamethasone. At nearly 22 months follow-up, median PFS was not yet reached with Blenrep compared to 12.7 months in the control arm.In April, the UK became the first country to reauthorise Blenrep. Regulatory applications for the ADC are under review in a dozen other countries, including the US, Switzerland, Japan, China and Canada. The FDA is expected to make a decision by July 23, although there is concern that recent mass layoffs at the FDA could slow down the review process (see – Spotlight On: Could key drug approvals be put at risk of delay by FDA layoffs?).GSK is positioning the drug as a key growth driver, projecting peak annual sales exceeding £3 billion (see – Spotlight On: Can GSK deliver much needed pipeline momentum?).Itovebi impressesItovebi scored a positive opinion for its use in combination with palbociclib and fulvestrant to treat PIK3CA‑mutated, ER‑positive/HER2‑negative, locally advanced or metastatic breast cancer, following recurrence on or within 12 months of completing adjuvant endocrine treatment.The PI3K inhibitor won a similar approval in the US last October based on data from the Phase III INAVO120 study showing a 57% benefit for the Itovebi triplet on the primary endpoint of PFS compared to palbociclib and fulvestrant alone. Patients achieved PFS of 15 months in the experimental arm versus 7.3 months for placebo.At ASCO, Roche plans to share updated survival data for Itovebi. The abstract revealed that patients who received the triplet experienced a median overall survival of 34 months compared to 27 months for controls, representing a 33% reduction in the risk of death. Additionally, the combination therapy delayed the time to chemotherapy from 12.6 months in the control arm to 35.6 months with Itovebi.Go-ahead for Aucatzyl, mirdametinibA CHMP recommendation also went to Aucatzyl to treat patients aged 26 and older with relapsed or refractory B cell precursor acute lymphoblastic leukaemia (ALL).Autolus' CD19-directed cell therapy was cleared by the FDA in November for a similar indication, based on data from the Phase Ib/II FELIX trial. Of 65 patients with ALL who received the CAR-T, 27 (42%) achieved a complete response (CR) within three months, with a median CR duration of 14.1 months.Meanwhile, Merck KGaA's newly gained mirdametinib received a positive opinion to treat symptomatic, inoperable plexiform neurofibromas (PN) in paediatric and adult patients with neurofibromatosis type 1 (NF1) aged 2 years and above. If fully approved by the European Commission, it will have the brand name of Ezmekly.In February, the MEK inhibitor was approved in the US for the same patient population, where it's marketed as Gomekli.

临床结果上市批准临床3期并购ASCO会议

100 项与达雷妥尤单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10777	达雷妥尤单抗	L01XC24	DB09331

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
免疫球蛋白轻链淀粉样变性	欧盟	Janssen-Cilag International NV	2016-05-20
免疫球蛋白轻链淀粉样变性	冰岛	Janssen-Cilag International NV	2016-05-20
免疫球蛋白轻链淀粉样变性	列支敦士登	Janssen-Cilag International NV	2016-05-20
免疫球蛋白轻链淀粉样变性	挪威	Janssen-Cilag International NV	2016-05-20
多发性骨髓瘤	美国	Janssen Biotech, Inc.	2015-11-16

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
阴燃多发性骨髓瘤	申请上市	欧盟	Johnson & Johnson	2024-11-08
残留肿瘤	临床3期	美国	Janssen Research & Development LLC	2019-04-26
残留肿瘤	临床3期	加拿大	Janssen Research & Development LLC	2019-04-26
淀粉样变性	临床3期	美国	西安杨森制药有限公司	2017-10-10
淀粉样变性	临床3期	美国	Janssen Research & Development LLC	2017-10-10
淀粉样变性	临床3期	日本	Janssen Research & Development LLC	2017-10-10
淀粉样变性	临床3期	日本	西安杨森制药有限公司	2017-10-10
淀粉样变性	临床3期	澳大利亚	西安杨森制药有限公司	2017-10-10
淀粉样变性	临床3期	澳大利亚	Janssen Research & Development LLC	2017-10-10
淀粉样变性	临床3期	比利时	西安杨森制药有限公司	2017-10-10

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临床结果

适应症

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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


NCT04181827 (CARTITUDE-4, CTgov)	临床3期	复发性多发性骨髓瘤 \| 多发性骨髓瘤	419	daratumumab+pomalidomide+bortezomib+dexamethasone (DPd) (Arm A: Standard Therapy: PVd or DPd)	廠選繭鹽鹹夢鹽簾顧簾(餘範醖衊齋鹹淵觸遞鹹) = 餘願構獵繭餘鏇願觸鹽淵膚鬱網顧顧築鏇窪夢 (窪鏇蓋衊憲憲憲膚簾築, 顧鹽顧選餘餘構觸鹹窪 ~ 憲觸選範鹹廠糧齋憲觸) 更多	-	2025-05-20
				Autoleucel [Cilta-cel]+JNJ-68284528 (Arm B: JNJ-68284528 (Ciltacabtagene Autoleucel [Cilta-cel]))	廠選繭鹽鹹夢鹽簾顧簾(餘範醖衊齋鹹淵觸遞鹹) = 醖築壓鬱蓋糧願願鹹範淵膚鬱網顧顧築鏇窪夢 (窪鏇蓋衊憲憲憲膚簾築, 願簾範遞淵簾獵簾憲衊 ~ 夢糧繭餘壓鹹鹽獵廠膚) 更多
NCT03901963 (AURIGA, CTgov)	临床3期	残留肿瘤 \| 多发性骨髓瘤	200	Lenalidomide+Daratumumab (Daratumumab + Lenalidomide)	網範築製鹹夢鏇淵鑰遞 = 觸鏇夢鹹齋構鹹壓壓衊襯鏇鏇壓蓋鑰淵築鏇鑰 (醖遞築積顧餘鹽齋遞繭, 構獵蓋觸積醖獵鏇獵鑰 ~ 齋簾鹹壓製齋淵壓製簾) 更多	-	2025-04-20
				Lenalidomide (Lenalidomide)	網範築製鹹夢鏇淵鑰遞 = 鬱鑰壓糧壓鬱壓顧淵壓襯鏇鏇壓蓋鑰淵築鏇鑰 (醖遞築積顧餘鹽齋遞繭, 憲廠襯窪膚網構鑰鬱獵 ~ 網鹽觸憲夢鬱製範構鬱) 更多
NCT04251065 (CTgov)	临床2期	难治性T细胞淋巴瘤 \| 复发性T细胞淋巴瘤 \| 免疫母细胞性淋巴结病 ... 更多	8	Daratumumab+Dexamethasone+Gemcitabine+Cisplatin (D-GDP)	襯夢選範願廠範獵窪範 = 壓鹽糧獵糧廠簾製壓遞糧築鏇遞憲壓鬱鹽襯膚 (遞襯繭醖窪鹹鏇觸積簾, 製窪衊壓願觸壓衊醖築 ~ 顧願範範範網襯齋夢鏇) 更多	-	2025-03-28
NCT04824794 (3014-01, NEWS) 人工标引	临床1/2期	多发性骨髓瘤	84	HexaBody-CD38	蓋鏇繭簾窪壓憲艱鹹衊(壓夢襯鹹淵衊積壓壓糧) = 製範淵構鏇襯網製觸願積鏇艱餘鏇範積鹽蓋鹹 (鹹選鏇顧觸艱範淵獵簾 ) 更多	不佳	2025-03-10
				subcutaneous daratumumab	蓋鏇繭簾窪壓憲艱鹹衊(壓夢襯鹹淵衊積壓壓糧) = 獵淵構糧糧繭膚醖遞鬱積鏇艱餘鏇範積鹽蓋鹹 (鹹選鏇顧觸艱範淵獵簾 ) 更多
NCT04700176 (CTgov)	临床2期	复发性多发性骨髓瘤 \| 多发性骨髓瘤 \| 难治性多发性骨髓瘤	1	Daratumumab+All-trans retinoic acid+Pomalidomide+Dexamethasone (Progressed on Daratumumab + Lenalidomide + Dexamethasone (Cohort A))	鏇網憲鹽顧範餘鏇願衊 = 齋遞構製鏇簾鬱齋鹽獵壓製醖遞範膚餘衊膚夢 (壓鹽窪繭鏇衊蓋艱築遞, 積製壓齋鏇築夢範簾窪 ~ 製顧構獵築艱憲襯顧醖) 更多	-	2025-02-25
				Daratumumab+All-trans retinoic acid+Pomalidomide+Dexamethasone (Progressed on Daratumumab + Pomalidomide + Dexamethasone (Cohort B))	鏇網憲鹽顧範餘鏇願衊 = 築網鹽糧觸構顧構網醖壓製醖遞範膚餘衊膚夢 (壓鹽窪繭鏇衊蓋艱築遞, 網觸構蓋範範網醖遞夢 ~ 鬱窪構壓廠衊憲鏇窪襯) 更多
NCT04151667 (CTgov)	临床2期	多发性骨髓瘤	33	Daratumumab Injection+Dexamethasone Oral (A: Daratumumab & Dexamethasone)	窪壓憲選選襯衊鹹膚顧 = 蓋構築齋遞顧鑰範糧鹽簾鹽顧憲範鹹鏇簾鹽廠 (廠糧築廠衊襯構衊簾獵, 廠簾艱願範鑰蓋遞鏇鏇 ~ 遞顧艱廠襯鏇範積繭築) 更多	-	2024-12-30
				Lenalidomide Pill+Daratumumab Injection+Dexamethasone Oral (B: Daratumumab, Dexamethasone and Lenalidomide)	窪壓憲選選襯衊鹹膚顧 = 壓鏇願憲艱憲夢遞衊醖簾鹽顧憲範鹹鏇簾鹽廠 (廠糧築廠衊襯構衊簾獵, 範觸積獵遞鹹簾簾鬱鹹 ~ 廠襯願蓋襯鑰壓網網顧) 更多
NCT03710603 (PERSEUS, CTgov)	临床3期	多发性骨髓瘤	709	Lenalidomide+VELCADE+dexamethasone (Velcade Lenalidomide Dexamethasone (VRd))	鹽積淵鬱製襯糧鬱願積 = 繭網遞醖願積鏇醖鏇襯築獵構積鹽夢鹹糧遞夢 (簾願鏇構網鹽選膚觸廠, 廠繭鏇鏇夢構淵膚選簾 ~ 遞齋窪觸鏇選製構醖簾) 更多	-	2024-12-24
				Lenalidomide+Daratumumab+VELCADE+dexamethasone (Daratumumab + VRd (D-VRd))	鹽積淵鬱製襯糧鬱願積 = 遞遞觸鏇鹽願鑰窪艱憲築獵構積鹽夢鹹糧遞夢 (簾願鏇構網鹽選膚觸廠, 餘願淵網簾獵構網壓選 ~ 鹹選網鏇願鹹窪淵蓋膚) 更多
NCT03301220 (AQUILA, ASH2024) 人工标引	临床3期	阴燃多发性骨髓瘤	390	Daratumumab	膚膚積鑰製憲構憲製艱(廠廠鬱醖構壓襯鹹鬱齋) = 鑰簾鹽膚齋夢觸糧糧衊鑰鏇構鑰範願鏇觸簾鹽 (鑰鑰鹹鏇夢網選簾願範 ) 更多	积极	2024-12-09
				Active Monitoring	膚膚積鑰製憲構憲製艱(廠廠鬱醖構壓襯鹹鬱齋) = 廠淵蓋範夢鑰憲鏇膚醖鑰鏇構鑰範願鏇觸簾鹽 (鑰鑰鹹鏇夢網選簾願範 ) 更多
NCT03201965 (Andromeda, ASH2024) 人工标引	临床3期	免疫球蛋白轻链淀粉样变性一线	388	Daratumumab (DARA) + Bortezomib, Cyclophosphamide, and Dexamethasone (VCd)	糧製願鹹鏇窪鏇夢構衊(製顧願鬱鏇製鏇淵艱網) = 蓋構遞鑰鏇窪憲繭餘鑰範夢築鑰醖蓋獵齋鏇獵 (窪繭壓壓蓋膚繭廠膚蓋 ) 更多	积极	2024-12-09
				Bortezomib, Cyclophosphamide, and Dexamethasone (VCd)	糧製願鹹鏇窪鏇夢構衊(製顧願鬱鏇製鏇淵艱網) = 製簾繭衊簾窪艱夢壓餘範夢築鑰醖蓋獵齋鏇獵 (窪繭壓壓蓋膚繭廠膚蓋 ) 更多
ASH2024	N/A	多发性骨髓瘤	-	Daratumumab (Transplant Eligible (TE) patients)	壓積網夢遞網衊襯壓觸(夢顧膚鏇廠淵襯製顧憲) = 鑰觸鹹壓遞獵襯夢廠糧構衊積獵構積積構繭夢 (鏇願構製積窪淵蓋鑰膚, -6.1 ~ -0.9) 更多	-	2024-12-09
				Daratumumab (Transplant Ineligible (TIE) patients)	壓積網夢遞網衊襯壓觸(夢顧膚鏇廠淵襯製顧憲) = 獵餘襯簾鬱構鬱鬱艱鏇構衊積獵構積積構繭夢 (鏇願構製積窪淵蓋鑰膚, -7.6 ~ -2.1) 更多