This phase II trial tests the safety and side effects of glofitamab and obinutuzumab and how well they work in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory) after receiving CD19-directed chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy is a form of immunotherapy where the immune system cell, T-cell, is changed to attack cancer cells. Glofitamab is a bispecific antibody that can bind to two different antigens at the same time. Glofitamab binds to CD3, a protein found on T cells (a type of white blood cell), and CD20 a protein found on B cells (another type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving glofitamab and obinutuzumab may be safe, tolerable, and/or effective in treating patients with relapsed or refractory mantle cell lymphoma after receiving CD19-directed CAR T-cell therapy.

开始日期2026-08-14

申办/合作机构

National Cancer Institute

NCT07326371

/ Not yet recruiting临床2期IIT

A Single-Center, Prospective Study Evaluating the Efficacy and Safety of Glofitamab Combined With CAR-T Therapy in Patients With High-Risk Relapsed/Refractory Large B-Cell Lymphoma

This study is a single-center, open-label, prospective study aimed at evaluating the efficacy and safety of Glofitamab combined with CAR-T therapy in patients with high-risk relapsed/refractory large B-cell lymphoma.

开始日期2026-03-01

申办/合作机构

上海交通大学医学院附属瑞金医院

NCT07233330

/ Not yet recruiting临床2期IIT

Obinutuzumab Treatment in Frequently Relapsing and Rituximab-Dependent Idiopathic Nephrotic Syndrome in Adults: a Fully Academic, Single-arm, Open, Prospective, Intervention Trial

This is a multicenter, open-label, single-arm Phase II clinical trial designed to evaluate the safety, efficacy, and immunological effects of obinutuzumab in adult patients with multi-relapsing, rituximab-dependent steroid-sensitive NS.
Obinutuzumab is a glycoengineered, humanized type II anti-CD20 monoclonal antibody that was initially developed to overcome rituximab resistance in B-cell malignancies. Obinutuzumab induced a longer and deeper B cell depletion than rituximab being able to deplete B cells in lymphoid tissue other than peripheral blood, as shown in both animal models and patients with chronic lymphocytic leukemia or kidney transplantation. Notably, obinutuzumab was found to be more efficient than rituximab in inducing B-cell cytotoxicity in-vitro, especially on naïve (IgD+CD27-) and switched (IgD-CD27+) memory B cells. This is a clinically relevant finding, because memory B cells are known to be associated with the risk of relapse after rituximab treatment in children with nephrotic syndrome. A recent retrospective study in 41 children [median (IQR) age: 10.6 (8.5-14.29) years] with steroid-dependent or frequently relapsing nephrotic syndrome, showed that treatment with obinutuzumab achieved B-cell depletion and sustained remission in 38 (93%) and 28 (68%) children at 12 and 24 months after treatment, respectively. Treatment was safe and well tolerated. Moreover, preliminary data indicate that obinutuzumab treatment can achieve complete or partial remission of the nephrotic syndrome in the large majority of adult participants with membranous nephropathy refractory to different immunosuppressive medications including rituximab, and even the human type 1 anti-CD20 antibody ofatumumab or the anti-CD38 antibody felzartamab (NCT05050214). Notably, obinutuzumab treatment achieved B-cell depletion and proteinuria reduction in all treated participants and persistent circulating anti-PLA2R antibody depletion in all participants with PLA2R-related disease even during the recovery of circulating B cells (NCT05050214). Conceivably, obinutuzumab could achieve remission of idiopathic nephrotic syndrome by inducing profound and sustained B-cell depletion, thereby inhibiting the production of anti-podocyte autoantibodies or the production of still unknown B-cell derived nephritogenic mediators and autoantibodies.
Thus, whether obinutuzumab treatment may achieve persistent remission also in adult participants with multi-relapsing, rituximab-dependent nephrotic syndrome, as previously reported in children, and as already observed in adult participants with refractory membranous nephropathy (NCT05050214), and whether this effect is associated with delayed recovery of switched memory B cells and emergence of B cells with a naïve phenotype as well as sustained reduction or depletion of circulating anti-podocyte antibodies is worth investigating.
In parallel to the evaluation of the phenotype of repopulating B cells, we will evaluate serum levels of the B-cell activating factor (BAFF). BAFF is a cytokine that orchestrates peripheral tolerance of B cells and promotes the survival of autoreactive B cells escaping central tolerance mechanisms. In participants with autoimmune diseases, such as systemic lupus erythematosus or rheumatoid arthritis, the relapse of disease activity after rituximab treatment has been associated with compensatory elevation of the B cell-activating factor BAFF levels. Elevated BAFF levels at baseline or during the follow-up may explain the resistance or dependency to anti-CD20 depleting antibodies in participants with idiopathic nephrotic syndrome.

开始日期2026-02-01

申办/合作机构

Istituto di Ricerche Farmacologiche Mario Negri

100 项与奥妥珠单抗相关的临床结果

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100 项与奥妥珠单抗相关的转化医学

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100 项与奥妥珠单抗相关的专利（医药）

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1,090

项与奥妥珠单抗相关的文献（医药）

2026-01-06·ASM Case Reports

Fulminant and fatal Trypanosoma cruzi reactivation in a patient with lymphoma

Article

作者: Satlin, Michael ; Westblade, Lars F. ; Mertelsmann, Anna ; Lukose, Georgi ; Pisapia, David J. ; Coyle, Christina ; Patel, Sanjay ; Marino, Jamie ; Rolon, Rebecca M. Marrero

ABSTRACT:

Background:

Trypanosoma cruzi is a protozoan parasite and the causative agent of Chagas disease. This case describes a fulminant and fatal reactivation of T. cruzi after immunosuppression in a patient with a history of follicular lymphoma, with parasitemia detectable in peripheral blood smears and parasites seen in multiple autopsy tissue specimens.

Case Summary:

A 61-year-old woman who had immigrated from El Salvador and was receiving obinutuzumab and zanubrutinib for follicular lymphoma in remission was admitted with persistent COVID-19 pneumonia. After multiple therapies for COVID-19, including more than 3 weeks of corticosteroid therapy for the possibility of organizing pneumonia, a peripheral blood smear identified T. cruzi trypomastigotes, and later amastigotes were identified in a bone marrow biopsy. The patient was treated with benznidazole but ultimately died. At autopsy, amastigotes were observed in multiple organs, including the heart, esophagus, stomach, small intestine, colon, bladder, and skeletal muscle.

Conclusion:

Most cases of Chagas reactivation are described in people living with HIV-1 or transplant recipients. Rarely, T. cruzi reactivation can occur in patients undergoing immunosuppressive therapies for malignancies or inflammatory states like COVID-19 infection, as seen in this case. If not recognized early, reactivation can be fatal despite antiparasitic treatment. Providers should consider screening patients from endemic areas who will start on immunosuppressive therapies. Repeating screening may be of value with periods of new immunosuppression. In patients with Chagas disease and malignancy, PCR from blood should be performed during enhanced immunosuppression so that preemptive treatment can be initiated prior to the presentation of fulminant disease.

2026-01-01·MOLECULAR THERAPY

Rapid immunization and antibody redesign platform discovers broadly neutralizing antibodies against non-immunized SARS-CoV-2 variant

Article

作者: Kamiyama, Akifumi ; Ito, Mizuho ; Hiratsuka, Masaharu ; Shimoya, Kazuto ; Yajima, Yuko ; Su'etsugu, Masayuki ; Kazuki, Yasuhiro ; Moriwaki, Takashi ; Wakasa, Yuko ; Tamura, Tomokazu ; Fukushima, Takato ; Tomizuka, Kazuma ; Kageyama, Seiji ; Watanabe, Arata ; Abe, Satoshi ; Fukuhara, Takasuke ; Kanai, Kyosuke ; Abe, Marina ; Suzuki, Rio ; Miyazaki, Natsumi ; Uno, Narumi ; Hamamichi, Shusei ; Uno, Kana

From COVID-19, we learned valuable lessons related to the development of broadly neutralizing antibodies (bnAbs). Here, we present a discovery platform termed Express Hu-mAb System that integrates a fully human Ab-producing transchromosomic (TC-mAb) mouse, a rapid immunization procedure, and a CHO cell-based mammalian display system (MDS) to generate bnAbs against the non-immunized SARS-CoV-2 variant in 60-90 days. Rapid 30-day immunization of a TC-mAb mouse resulted in increased titers, elevated antibody concentration, and production of anti-serum that neutralized the non-immunized BA.1. Single B cell analysis without using fluorescent antigen probe identified clonotypes that recapitulated immune responses associated with the COVID-19. Importantly, we generated 25 bnAb candidates based on the abundance of sequence reads, determined 14 binders (56%), and identified clonotype 11 as a bnAb that neutralizes the non-immunized BA.5 in 60 days. Next, exploiting a TC-mAb mouse whose anti-serum neutralized only the Wuhan strain, we constructed a chain-shuffled immunoglobulin cDNA library with sufficient diversity of 4.3-6.2 × 10⁴ CHO cells. We then applied the MDS to redesign bnAb candidates, and identified M5419S09Ab01 that neutralizes the BA.5 in 90 days. Taken together, this work demonstrates speed, efficiency, and simplicity of our platform to discover bnAbs against the phylogenetically distinct viral variant with optimal developability and manufacturability.

2026-01-01·Case Reports in Hematology

Successful Zanubrutinib Monotherapy in a Rare CNS Presentation of Relapsed CLL

Article

作者: Pinilla-Ibarz, Javier ; Mediavilla-Varela, Melanie ; Kunta, Vishaal ; Ammad-Ud-Din, Mohammad

Background:

Central nervous system (CNS) involvement is an infrequent complication of chronic lymphocytic leukemia (CLL), occurring in less than 1% of cases. We report a case of a 63‐year‐old male with a history of CLL previously treated with ibrutinib but discontinued early due to intolerance. As a result, the patient was then treated with obinutuzumab plus venetoclax, achieving undetectable minimal residual disease (MRD) but relapsed after 2 years with CNS involvement.

Case Presentation:

The patient initially presented to the emergency department with confusion and altered mental status. Magnetic resonance imaging (MRI) of the brain revealed abnormal subcortical hyperintensities and leptomeningeal enhancement concerning leukemic infiltration. Lumbar puncture confirmed malignant CD5+ CLL cells in the cerebrospinal fluid (CSF), and a bone marrow biopsy revealed 50%–60% CLL involvement. Zanubrutinib 320 mg daily was initiated. The patient exhibited marked cognitive improvement within full resolution after four weeks of therapy. Follow‐up MRI after 8 weeks showed full resolution of CNS, lesions with repeat LP demonstrating CSF cleared of CLL cells. He remains in complete remission with continued daily zanubrutinib 6 months follow‐up; no significant adverse effects were observed.

Conclusion:

This case highlights the rare occurrence of CNS involvement in CLL and is the first to demonstrate successful CNS disease eradication with zanubrutinib monotherapy.

794

项与奥妥珠单抗相关的新闻（医药）

2026-01-27

·记忆无法承载

来自JPM的商业思考——罗氏

2026罗氏JPM的分享题为：带来下一个创新的周期，是由罗氏制药的head Teresa带来的。首先，罗氏表达了2026年要做好三件事：第一件事，最大化目前已经上市产品的价值，它们将会驱动罗氏的业务持续增长到2028年。目前罗氏有17个重磅产品驱动着不同业务领域的增长，如何评价一个产品是不是重磅产品呢？罗氏的标准是年销售额可以达到10亿瑞士法郎。那么这17个重磅产品分别是什么呢？我们从罗氏最强大的领域开始看起，肿瘤：肺癌Alecensa (安圣莎)，血液肿瘤Venclexta (维奈克拉，艾伯维合作)，淋巴瘤Polivy (优罗华)，实体瘤Tecentriq (泰圣奇)，乳腺癌Perjeta (帕捷特)，乳腺癌Phesgo(帕妥珠单抗/曲妥珠单抗组合)，乳腺癌Kadcyla (赫赛莱)；当然还有曾经带给罗氏辉煌的“三驾马车”，虽然面临生物类似物竞争，但在 2024 财年销售额仍超过 10 亿瑞郎，它们是：实体瘤Avastin (安维汀)，乳腺癌Herceptin (赫赛汀)，淋巴瘤MabThera (美罗华)。然后是血液：血友病Hemlibra (艾美赛珠单抗)；神经科学：多发性硬化Ocrevus (奥瑞珠单抗)，脊髓性肌萎缩症Evrysdi (艾满欣) 免疫学：脊髓性肌萎缩症Evrysdi (艾满欣)，过敏Xolair（茁乐，诺华合作），肾科Gazyva (佳罗华，淋巴瘤也有涉及)，类风关Actemra (雅美罗) 眼科：眼底黄斑疾病Vabysmo (罗视佳) 所以，结合这个，我们可以看到曾经和当下的罗氏，它什么最强了吧？今天这套片子将帮助我们看到罗氏的未来。第二件事，做好关键产品的上市，那些即将上市的产品和适应症也会进一步驱动公司业务自26年以后的增长。第三件事，推动新一代产品分子开发的进展，这里罗氏特意用了一个词，post bar，说明这些分子是罗氏通过谨慎评估筛选出来的，是有一定标准的，结合举例，自然是患者群体够大，未被满足需求够高的疾病领域和产品，比如阿尔兹海默症和减肥。可能是眼红礼来这几年在资本市场的表现，所以罗氏也要把战略重点触及到这些一旦取得进展便足以撬动增长的疾病领域。所以，罗氏正在努力拓宽并使自己的管线更加多样化，而不是像之前更侧重于聚焦在肿瘤，这里它用了一个词，transformational potential，想必这里的transformational不仅仅意味着推动治疗领域的变革，同时也可以理解为罗氏带来巨大的变革。那么做好这三件事的基石又是什么？罗氏认为首先是在做生意上的高度自律，这很好理解就是财务自律，要控制财务预算嘛，其次就是在做研究上的高度严谨，这个研究我觉得有两个方面，一个是科学证据数据上的严谨，一个是端对端科学数据转化为商业价值上的严谨。只有这样才能持续带来增长。不同的公司风格和文化不一样，个人认为罗氏的基因文化就是科学驱动下的产品研发和创新。罗氏大约有60%的研发管线和销售收入是来自于外部合作产生的。罗氏对自身内部的定义是：罗氏制药、基因泰克和之前并购来的Spark，而日本中外制药，罗氏对其定义为一种战略联盟的合作，所以来自中外制药的产品和销售额也包括在这60%内，从这张图上可以看出日本中外制药也给罗氏带来了几个非常好的产品，比如：安圣莎，舒友利乐。罗氏把目前上市的产品分为了四类，分别是：1.临床开发阶段买过来的，2.有外部技术合作的产品，3.日本中外制药开发的产品，4.罗氏自己开发的产品。所以，我们可以看到有纯正罗氏基因的产品并不多，比如：泰圣奇，OCREVUS，LUSUMIO，COLUMVI，ITOVEBI；而买过来的产品就很多了，这里就不列举了；我们再来看有外部技术合作的产品：优罗华：我们知道它是一个ADC类药物，它是罗氏与Seagen公司合作开发的产品，罗氏通过基因泰克获得了 Seagen 技术的授权，负责产品的后续临床开发、制造和商业化。作为合作的一部分，罗氏在产品达到特定临床或监管里程碑时需向 Seagen 支付里程碑款项，并在产品上市销售后支付特许权使用费。 Phesgo：罗氏采用了Halozyme的ENHANZE® 皮下递送技术（利用重组人透明质酸酶），使得原本需要数小时静脉滴注的药物可以在几分钟内完成皮下注射。 Vabysmo：全球首个获批用于眼科治疗的双特异性抗体，采用了 CrossMAb 技术平台。该平台最初是由罗氏旗下的德国研发中心（Roche Penzberg）开发的，但由于罗氏与中外制药 (Chugai) 之间长期的战略技术交换协议，这一技术在开发过程中整合了大量的外部工程学专长。在演示文稿中，Vabysmo 被标注为合作产品，是因为它的分子结构设计涉及了复杂的抗体工程授权，用于同时实现对两个靶点（VEGF-A 和 Ang-2）的精准结合。所以，这项技术也是来自于日本的中外制药（Chugai），它不仅仅是一个药企，它更像是罗氏体系内的“高端技术研究院“。在抗体工程，尤其是双特异性抗体的结构设计、半衰期延长和工业化生产方面，中外制药的技术平台处于世界第一梯队，是罗氏维持其在生物药领域领导地位的关键支柱。罗氏这种”买买买“及外部合作的策略，加速了它管线开发的速度，当下和未来它还是会有很多类似的外部合作，演示文稿里面也列举了一些。接下来，罗氏就详细罗列了已经上市的产品在2025年的表现，其实就是前面片子里17个重磅产品中14个的表现，那为啥少了三个，自然是“廉颇老矣，尚能饭否”的“三家马车”，但“老将廉颇”还是很能打的，这么多年给罗氏创造了无数的现金流，到目前为止年销售额还是在10亿瑞郎以上。从这张图我们可以看出来，罗氏的肿瘤产品的销量还是占据了半壁江山，但是增长已经远远不及左半边领域的非肿瘤产品，可预测的是肿瘤产品的销售额和占比将会被非肿瘤产品管线在不久的将来超越。新产品上，片子上罗列了四大领域，五个分子，2026年罗氏可能会有三个新产品上市，我们知道Gazyva和Satralizumab目前已经上市，所以，2026年潜在可以上市的新产品是giredestrant，fenebrutinib，vamikibart，分别会为罗氏在乳腺癌，中枢神经和眼科领域贡献销量，而已经上市的两个产品将会在新的领域免疫和眼科上老树开新花。接下来，让我们来详细聊聊这些产品，首先是乳腺癌产品Giredestrant，它是新一代口服选择性雌激素受体降解剂（SERD），它通过降低雌激素受体（ER）数量并阻断其信号传导来发挥作用的内分泌治疗药物。与传统的他莫昔芬（SERM）仅阻断受体不同，SERD 能够直接“清除”受体本身。在左边这张图中，我们可以看到罗氏正试图以Giredestrant 作为内分泌治疗的基础骨干，通过针对不同疾病阶段和耐药机制的组合疗法，取代现有的标准治疗。对于早期雌激素受体阳性乳腺癌，III 期临床研究lidERA显示对于中高危患者，术后使用 Giredestrant或Giredestrant联合CDK4/6抑制剂可以带来更好的效果。而对于晚期/转移性雌激素受体阳性乳腺癌，无论前序是否接受过芳香化酶抑制剂的治疗，或是对芳香化酶抑制剂敏感或耐药的患者，Giredestrant联合CDK4/6抑制剂的方案正在一线治疗关键临床探索中去证明其潜在的疗效和安全性。而在二线，Giredestrant联合依维莫司 (mTOR 抑制剂)已经证明了其积极的疗效。而Giredestrant联合GDC-1498(一款高效且高选择性的 CDK4 抑制剂)的疗效目前也在探索中。总之，在罗氏的规划中，Giredestrant及其联合治疗将会成为改变雌激素受体阳性乳腺癌从早期到晚期治疗的新范式。同时，罗氏还介绍了其在乳腺癌上不同信号通路的潜在BIC分子， Giredestran作为内分泌治疗（ET）的Backbone； Itovebi(PI3K/AKT/mTOR)作为一款针对PIK3CA突变患者的口服精准治疗药物，具有极高的靶向选择性，能在提供强效抗肿瘤作用的同时减少毒性（如高血糖风险），允许在标准剂量下与内分泌疗法和 CDK4/6 抑制剂联用，且已在临床中显著延长了患者寿命； RG6794 (GDC-4198)是一款高效的 CDK4 抑制剂，除了抑制 CDK4，它还具有显著的抗 CDK2 活性。这旨在解决目前临床上对CDK4/6 抑制剂产生耐药的问题； ZN-1041是一款高度选择性、具备血脑屏障通透性的 HER2 酪氨酸激酶抑制剂（TKI），专门针对乳腺癌脑转移患者，能够有效渗透入脑，且可与现有的抗 HER2 基础疗法联用。总之，罗氏试图通过这些针对不同耐药机制和病理特征的分子组合，为乳腺癌患者提供定制化的转型治疗方案，从而重新定义治疗范式。我们再来聊聊罗氏的下一个明星分子，Fenebrutinib，它是一种针对多发性硬化症（MS）的口服、非共价（可逆）BTK抑制剂。它也是唯一一个在RMS(复发型多发性硬化症)和PPMS(原发进展型多发性硬化症) 临床试验中都取得了阳性结果的药物。很多药物可能只在RMS上有效，但在更难治的 PPMS 上折戟，Fenebrutinib 在这两个领域都拿到了“入场券”。左边的图向我们展示了其双重的作用机制：针对复发型病理 (Relapsing biology)，Fenebrutinib作用于外周的 B 细胞和巨噬细胞，减少急性炎症发作；针对进展型病理 (Progressive biology)，Fenebrutinib作用于中枢神经系统内的 B 细胞和小胶质细胞，而小胶质细胞的过度激活被认为是导致 MS 持续残疾进展的关键。最终Fenebrutinib通过双管齐下，显著降低残疾累积。也许正是其双重的作用机制，使其在两个适应症上都做出了阳性的结果，同时又因为它是口服剂型而不用住院输液，使其潜在使用率和使用版图都得以扩增。而右边的图显示，与竞争对手相比，Fenebrutinib拥有更好的PK曲线，使其可以在游离血浆中的浓度更高，而只有游离并未与蛋白质结合的药物分子才能穿过血脑屏障进入大脑，去攻击那些躲在大脑里的病灶。这张幻灯片详细列出了罗氏预计在2026年取得注册进展和临床试验结果的分子及对应的疾病领域适应症和方案，特别指出，刚刚提到的Giredestrant联合依维莫司 (mTOR 抑制剂)在CDK抑制剂经治的雌激素受体阳性/HER2阴性晚期及转移性乳腺癌的治疗申请将在今年向FDA递交。接下来就聊到了减肥，前面在JPM礼来的文章中已经详细讲到了这个领域，我们来看看罗氏的布局。罗氏要成为这个领域世界前三的玩家，五个分子的相关数据将会在2026年公布，以支持它们的三期临床研究。这五个分子是： CT-388 (GLP-1/GIP 受体双重激动剂)，直接对标礼来的 Mounjaro (替尔泊肽)。它是罗氏减肥管线中的“重炮手”，在初期研究中表现出了极强的减重效果和良好的耐受性。 CT-996 (口服小分子GLP-1 受体激动剂)，这是目前市场最看好的方向之一，旨在摆脱“打针”的麻烦。它主要针对那些不愿注射或处于体重维持阶段的患者。 CT-868(GLP-1/GIP 受体双重激动剂)，专注于合并 1 型糖尿病的肥胖患者。这类人群的血糖和体重管理非常复杂，是目前市场上未被满足的临床需求。 Petrelintide (长效Amylin粉样蛋白类似物)，这是非肠促胰岛素Non-incretin通路，它可以与GLP-1药物联用，产生协同减重效果。在减轻体重的同时，具有更好的耐受性（更少的恶心呕吐），并且在保持肌肉质量方面可能更有优势。 Emugrobart (抗肌抑素Anti-myostatin抗体)，解决减肥药最大的副作用——肌肉流失，目标就是实现“只减脂肪，不减肌肉”的高质量减重。这五个 NMEs 的 Ph II 数据都将在 2026 年集中公布，而这些数据来自六大方面：耐受性 (Tolerability)，现有的减肥药常导致恶心、呕吐等胃肠道副作用，导致患者停药。减重天花板效应 (Ceiling effect)，患者在使用现有药物 12-18 个月后，体重往往不再下降，进入平台期。减重维持 (Weightmaintenance)，一旦停止使用 GLP-1 药物，患者体重极易快速反弹。反应不佳 (Suboptimal response)，约有 20% 的患者对目前的肠促胰岛素（GLP-1 类）疗法反应平平。肌肉流失 (Lean muscle loss)，快速减重过程中，肌肉流失占比过高（可达 40%），影响代谢和健康。相关并发症 (Comorbidities)，70% 以上的肥胖患者伴有脂肪肝（MASH）、心血管疾病等并发症。接下来就聊到了每家公司都要提及的2030，罗氏在2030年之前可能会上市19个新产品，而之前聊到的post Bar新产品包括：afimkibart, NXT007, cevostamab, CT-388, CT-868, CT-996, petrelintide, zilebesiran, peozafermin, trontinemab, prasinezumab，这个Bar从这张图上看来就是年销售额超过10亿瑞士法郎，基于这个商业评估标准，这些分子Post-bar的评估中被筛选进入到最终的临床开发中，而它们的关键临床数据最快可能会在2027年陆续公布。从这张图不难看出，从商业角度，罗氏未来的绝对重点会是CVRM和Neurology，当然了，也要看后续的研发进展，是否都能成功，就看罗氏的押注能不能中了。但也不经要问，眼科领域会不会是一个阶段性产物，昙花一现的领域呢？最后，罗氏比较传统，来了个总结，呼应了一下开头2026年要做好的三件事，包括聚焦当下产品的商业表现，做好接下来一些关键产品的上市，以及最为关系到罗氏未来的新一代产品的开发，以带来transformational的可能。当下，2025年的表现一切顺利，已经上市的产品将会继续驱动罗氏的业务增长到2028年，同时2026年开始陆续上市的新产品将会驱动后续罗氏业务的进一步增长，因此当下，罗氏要做好自律，换句话说，就是财务控制，不要乱花钱，把钱花在刀刃上，那自然是关键产品的研发以及卓越的商业运营。 2025年，罗氏有12项阳性数据的公布，包括刚刚提及的乳腺癌和多发性硬化。同时还有三个产品进入到关键临床三期阶段，这些都会为罗氏后续业务增长带来潜在的推动力。展望2026年，罗氏将继续聚焦在新产品上市以及商业执行上，同时会期待10个三期数据的公布，并有多个新产品进入到三期临床阶段。特别要强调的是减肥，其产品将会在2026年进入到late stage的开发，为未来成为该领域前三的潜在玩家而努力！而最后一张就是罗氏的惯例了，所有对外沟通的幻灯都是以这张作为结束，翻译成中文就是以患者之需而行，这其实也反映了它的价值观，但患者的需求千千万，如果完全按照商业价值去考量，那可能很多不到10亿瑞郎年销售额的产品和适应症，将在一定程度上被排在行动的后面，甚至被放弃。不得不说，作为一家需要为股东和董事会负责的上市公司，这也是没有办法的事情，资本是逐利的。假设我们把患者需求分为两个维度：1.疗效安全性没有得到满足，还有很大的提升空间；2.患者群体有庞大的基数，以等待更好药物的治疗。显然，大公司聚焦的都是两者兼备，或者患者足够多及时份额不高也可以有很好的现金流的领域。少有只满足第一点，但第二点无法被满足的领域，这种有一个前提，就是疗效安全性数据突破性颠覆式进展，足以取得极高的患者份额甚至对原有标准治疗完全取代，还得没有后来竞争者，在这个前提基础下，再通过财务测算看年销售额是否可以达到一定的标准。因此，对于人数很少，但治疗需求又很大的群体患者来说，比如罕见病，又有谁去为他们发声，为他们付出行动，并努力研发更好的药物呢？这也许也是一种存在主义的市场需求和机会，的确还是有公司在探索的。首先，我们要向聚焦在罕见病领域的公司致敬，也要向扎根在某一领域深耕而不轻易变换方向的公司致敬。但如果权力机构，比如国家和政府审批单位，不帮助他们规避政策上的风险，不给予合理的政策和价格引导支持，那我想能坚持下来的厂家不会很多。亚当·斯密在《国富论》中提到，“他追求的仅仅是他个人的利益，而在这种场合，像在其他许多场合一样，他被一只看不见的手引导着去促进一个他原本并无意追求的目的……他追求自己的利益，往往能比他真正出于本心想促进社会利益时更有效地促进社会的利益。” 其核心逻辑是：每个主体在追求自身利益的同时，会被一只“看不见的手”引导，最终在客观上促进了社会整体利益的增加。但局部的患者利益，一定程度上还是需要公权去维护，否则在社会和治疗领域进步的同时，这部分患者的需求可能就很难得到满足了。。。

生物类似药一致性评价上市批准

2026-01-27

·肾脏病与透析肾移植杂志订阅号

论著|奥妥珠单抗治疗难治及复发性狼疮肾炎的疗效观察

张芮枫王晶晶汪欣悦陈独群涂远茂章海涛 DOI：10.3969/j.issn.1006-298X.2025.06.003 ［基金项目］国家重点研发计划项目(2024YFC2511002);院管课题临床研究专项(2024LCYXXH009) [作者单位]南京大学附属金陵医院(东部战区总医院 )硕士研究生(张芮枫) 国家肾脏疾病临床医学研究中心(南京,210016) ［通信作者］章海涛(E-mail:htzhang163@163.com) 摘要目的:探索性观察奥妥珠单抗(OBZ)治疗难治及复发性狼疮肾炎(LN)患者的临床疗效与安全性。方法:回顾性分析2023年11月至2024年12月于国家肾脏疾病临床医学研究中心接受OBZ治疗的LN患者资料。治疗方案:第1天、第15天接受1.0 g OBZ,第6个月根据缓解情况或B细胞重建决定是否追加OBZ。主要结局为累积肾脏缓解率。结果:共纳入9例患者(复发7例,难治2例),女性8例。中位随访12个月,所有患者均获得肾脏缓解,其中4例获得完全肾脏缓解(CRR)。治疗6个月时尿蛋白定量由基线1.97(1.78～8.94)g/d降至0.79(0.46～1.09)g/d,血清补体及系统性红斑狼疮疾病活动指数(SLE-DAI)评分均明显改善,肾功能保持稳定。治疗3个月所有患者外周血B细胞均呈完全耗竭状态,6个月仅1例患者出现B细胞重建。9个月时泼尼松剂量降至7.5 mg/d。治疗期间无严重不良事件发生。结论:OBZ治疗难治及复发性 LN 患者,能够有效获得肾脏缓解,改善免疫学指标及SLE疾病活动,治疗期间耐受性及安全性良好。仍需前瞻性大样本研究进一步证实OBZ在这类患者中的疗效。关键词难治性狼疮肾炎奥妥珠单抗 B细胞耗竭肾脏缓解Efficacy of Obinutuzumab in patients with refractory and relapsing lupus nephritis ZHANG Ruifeng, WANG Jingjing, WANGXinyue, CHEN Duqun, TU Yuanmao, ZHANG Haitao National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University,Nanjing 210016, China Corresponding author：ZHANG Haitao(E-mail:htzhang163@163.com) ABSTRACT Objective:To evaluate the clinical efficacy and safety of Obinutuzumab (OBZ) in the treatment of patients with refractory and relapsing lupus nephritis (LN). Methodology:We retrospectively analyzed data from LN patients treated with OBZ at the National Clinical Research Center for Kidney Diseases from November 2023 to December 2024. Treatment regimen: 1.0 g of OBZ was administered on days 1 and 15, whether to administer additional OBZ was based on remission status or B-cell reconstitution at month 6. The primary outcome was the cumulative renal response rate.Results:A total of 9 patients were included (7 relapsing LN, 2 refractory LN) with 8 females. The median follow-up was 12 months. All patients achieved renal response, and 4 patiens acheived complete renal response (CRR). At month 6, the median proteinuria decreased from a baseline of 1.97(1.78～8.94)g/d to 0.79(0.46～1.09)g/d. Serum complement levels and Systemic Lupus Erythematosus Disease Activity Index (SLE-DAI) scores showed significant improvement, while renal function remained stable. All patients achieved complete peripheral B-cell depletion within 3 months, with only one patient showing reconstitution at month 6. The median prednisone dosage was tapered to 7.5 mg/d by month 9. No serious adverse events occurred during the treatment period. Conclusion:OBZ therapy could effectively improve renal response in patients with refractory and relapsing LN, with alleviated immunological parameters and disease activity. The patients showed favorable tolerability and safety during the treatment. The large prospective studies are needed to confirm the efficacy of OBZ in these special patients. Key words refractory lupus nephritis Obinutuzumab B-cell depletion renal response 狼疮肾炎(LN)是系统性红斑狼疮(SLE)最严重并发症之一,也是导致患者进展至终末期肾病(ESKD)的主要原因。10%～30%的患者最终仍进展至ESKD[1]。目前已有的诱导治疗方案完全肾脏缓解(CRR)率偏低,Aspreva狼疮管理研究(ALMS)及贝利尤单抗治疗LN关键研究(BLISS-LN)等数据显示,治疗6～12月后的CRR率仅为20%～40%,且20%～30%的患者对传统治疗无效[2-3]。此外,LN病程迁延,30%～50%的患者在获得缓解后的3～5年内出现肾脏复发[4-6]。反复发作及难治状态加速了ESKD的进展[7]。近年来,B细胞在SLE及LN发病机制中的核心作用逐渐明确,相关生物制剂在临床上取得显著疗效[8]。2024年肾脏病改善全球预后组织(KDIGO) 和2025年《欧洲抗风湿病联盟SLE肾脏受累管理推荐意见》均推荐在LN治疗中联合应用靶向B淋巴细胞的生物制剂[9-10],其中抗CD20单克隆抗体最具代表性。利妥昔单抗(RTX)治疗LN评估研究(LUNAR)显示[11],RTX未能显著提高CRR率,事后分析认为与B细胞耗竭不彻底、随访时间短及患者间应答差异较大有关。奥妥珠单抗(OBZ)为人源化的Ⅱ型新一代抗CD20单克隆抗体,具有更强的抗体依赖性细胞介导的细胞毒作用(ADCC)和直接杀伤作用,且对补体依赖的细胞毒性作用(CDC)依赖性及免疫原性风险更低[12]。OBZ治疗活动性LN的Ⅲ期临床试验(REGENCY)研究证实,在标准治疗基础上联合OBZ治疗显著提高CRR率(46.4%),而对照组仅为33.1%[13]。FDA于2025年10月正式批准OBZ用于LN治疗,为LN患者提供了新的治疗选择。REGENCY研究的亚组分析显示,对于既往确诊的LN患者,联合OBZ治疗相较于标准治疗并未显示出显著优势。目前关于OBZ在难治性LN人群中的应用仍缺乏充分的临床证据。本研究回顾性分析单中心数据,评估OBZ在难治及复发性LN患者中的疗效与安全性。对象和方法研究对象纳入2023年11月至2024年12月在国家肾脏病临床医学研究中心接受OBZ治疗的9例LN患者。纳入标准:(1)肾活检病理类型为Ⅲ/Ⅳ型±Ⅴ型或Ⅴ型LN;(2)经过标准治疗无效或者复发的患者;(3)尿蛋白定量≥1.0 g/d;(4)随访时间≥9个月。本研究获得东部战区总医院伦理委员会批准(批准文号:2025DZKY-011-01)。治疗方案及观察指标 OBZ治疗方案:1.0 g,第1天、第15天静脉输注;第6个月根据是否获得CRR或B细胞重建决定是否追加OBZ。OBZ给药前均接受甲泼尼龙 80 mg、异丙嗪 25 mg和对乙酰氨基酚 900 mg预处理。收集患者基线及随访资料(第3个月、第6个月、第9个月、第12个月及末次访视),包括年龄、性别、病程、SLE疾病活动指数(SLE-DAI)评分等;24 h尿蛋白定量、血清白蛋白(Alb)、血清肌酐(SCr)、估算的肾小球滤过率(eGFR)、抗dsDNA抗体、血清C3、C4、IgG、CD4+T淋巴细胞及CD20+B淋巴细胞计数等。相关定义 (1)肾脏复发:获得CRR后尿蛋白定量≥1.0 g/d,伴或不伴eGFR降低;或获得部分肾脏缓解(PRR)后尿蛋白定量倍增,伴或不伴血尿增加或eGFR降低[14]。(2)难治性LN:激素联合一种及以上免疫抑制剂足剂量、足疗程(通常6个月)治疗后,仍未达到PRR[15]。(3)CRR:尿蛋白定量<0.5 g/d,或尿蛋白/肌酐比(uPCR)<0.5 g/g,且eGFR较基线下降≤10%～15%或eGFR≥90 mL/(min·1.73m2)[15]。(4)PRR:尿蛋白定量较基线下降≥50%且<3.5 g/d,或uPCR下降≥50%且<3.0 g/g;eGFR较基线下降≤10%～15%,或eGFR≥90 mL/(min·1.73m2)[15]。(5)B细胞耗竭指外周血CD20+B淋巴细胞计数<5个/μL;B细胞重建指外周血CD20+B淋巴细胞计数≥5个/μL。统计学分析数据分析采用《GraphPad Prism》软件。计数资料以例数(百分比)表示;符合正态分布的计量资料以均数±标准差表示,非正态分布的计量资料以中位数(四分位间距)表示。结果基线资料共纳入9例患者,男性1例、女性8例,LN的起病中位年龄23岁,中位病程11.5年,其中Ⅳ型3例、Ⅴ型3例、Ⅳ+Ⅴ型2例、Ⅴ+Ⅲ型1例。复发7例,难治2例。各例患者基线情况见表1。仅例7基线接受甲泼尼龙冲击治疗。例5有糖尿病病史,基线及后续随访中未接受激素治疗。表1 9例难治及复发性LN患者的基线临床资料 LN:狼疮肾炎;SLE:系统性红斑狼疮;SLE-DAI:系统性红斑狼疮疾病活动指数;Alb:血清白蛋白;eGFR:估算的肾小球滤过率;SCr:血清肌酐;P:泼尼松;HCQ:羟氯喹;FK506:他克莫司;OBZ:奥妥珠单抗;MP:甲泼尼龙;LEF:来氟米特;CTX:环磷酰胺;MMF:吗替麦考酚酯;BEL:贝利尤单抗;AZA:硫唑嘌呤:TW:雷公藤多苷;RTX:利妥昔单抗疗效评估 9例患者中位随访12个月,均获得肾脏缓解(CRR+PRR),首次获得肾脏缓解的中位时间为6个月。其中4例获得CRR,获得CRR的中位时间为9个月。第3个月3例获得肾脏缓解,CRR 1例;第6个月6例获得肾脏缓解,CRR 1例;第9个月6例获得肾脏缓解,CRR 3例;第12个月4例获得肾脏缓解,CRR 2例。临床指标变化 OBZ治疗后,尿蛋白定量在6个月内持续下降,基线、第3个月、第6个月分别为1.97(1.78～8.94) g/d,1.61(0.87～1.87) g/d,0.79(0.46～1.09) g/d,此后均<1.00 g/d(图1A)。Alb由基线26.18±4.36 g/L升至第3个月的38.94±5.44 g/L,此后均>40.00 g/L(图1B)。SCr和eGFR早期出现轻度波动,第9个月起保持稳定,基线和第12个月的SCr分别为64.53±17.68 μmol/L和67.19±17.77 μmol/L;eGFR分别为104.60±24.88 mL/(min·1.73m2)和103.00±25.84 mL/(min·1.73m2)(图1C、D)。图1 患者尿蛋白定量(A)、Alb(B)、SCr(C)、 eGFR (D)随时间变化情况 Alb:血清白蛋白;SCr:血清肌酐;eGFR:估算的肾小球滤过率治疗期间,血清C3、C4逐渐升高。C3由基线 0.51(0.40～0.70) g/L升至第12个月的 0.95(0.70～1.23) g/L(图2A);C4则由0.13(0.09～0.17) g/L升至 0.23(0.15～0.33) g/L(图2B)。基线仅2例患者(例6和例9)抗dsDNA抗体阳性,例9在治疗期间抗体持续阳性,例6在第6个月抗体转阴;而例1在第12个月抗dsDNA抗体转为1∶16阳性。SLE-DAI评分亦呈下降趋势,由基线10.0(8.0～13.0)分降至第9个月的4.0(4.0～8.0)分(图2C)。图2 患者血清C3 (A)、C4 (B)、SLE-DAI (C)、 CD20+B淋巴细胞计数 (D)随时间变化情况 SLE-DAI:系统性红斑狼疮疾病活动指数基线中位血清IgG为5.40(3.47～6.80)g/L,第6个月升至7.78(5.96～9.58)g/L;CD4+ T淋巴细胞计数基线为519(383～818)个/μL,随访第3个月为1 074(414～1 189)个/μL、第6个月768(469～1 091)个/μL、第9个月606(472～940)个/μL、第12个月549(439～811)个/μL。 B细胞耗竭情况所有患者在3个月内均达到外周血B细胞完全耗竭,后续随访期间,3例患者出现B细胞重建(第6个月1例,第9个月2例)。5例患者在第6个月接受OBZ追加治疗,仅1例出现B细胞重建。其中,例5共接受5.0 g OBZ治疗:该患者第6个月获得PRR,同时出现B细胞重建(87个/μL),第24周、第26周追加OBZ 1.0 g 治疗,第9个月实现二次耗竭,但第12个月又出现B细胞重建(101个/μL)并伴肾脏复发,再次给予 OBZ 1.0 g 治疗(图2D)。随访情况随访9～15个月,仅例5在第12月出现肾脏复发(尿蛋白定量3.69 g/d,SLE-DAI 4分)。8例接受泼尼松治疗的患者,其激素剂量分别为基线20.0(10.0～30.0) mg/d,第3个月10.0(10.0～20.0) mg/d,第6个月10.0(8.1～10.0) mg/d,第9个月减至7.5(5.0～7.5) mg/d,第12个月10.0(1.3～10) mg/d。除泼尼松及羟氯喹作为基础治疗外,本组患者合并使用的免疫抑制剂主要为吗替麦考酚酯(MMF)和他克莫司(FK506)。安全性分析所有患者均未出现输注相关反应(如短暂发热、皮疹),无严重感染事件、血液学毒性及肝功能损害等不良反应,也无死亡病例。例5累计接受5 g OBZ治疗,未出现并发症。讨论本研究回顾性分析了OBZ在难治及复发性LN患者中的应用,结果发现9例患者均快速实现临床缓解,6例患者持续维持B细胞耗竭。所有患者在末次访视均获得肾脏缓解,第9个月的CRR率达37.5%(3/8),与OBZ治疗LN的Ⅱ期临床试验(NOBILITY)在第52周的CRR率(35%)以及REGENCY试验第76周的CRR率(46%)相近[13,16]。尿蛋白定量在治疗6个月内明显下降,Alb升高,肾功能保持稳定,C3和C4水平逐步升高,SLE-DAI评分下降,表明OBZ能有效治疗难治和复发性LN。 B细胞耗竭是OBZ发挥治疗作用的核心环节。本研究中,所有患者在3个月内均实现B细胞完全耗竭,6个月内仅1例患者出现B细胞重建。这一结果与膜性肾病等研究一致[17-20],表明OBZ能实现早期、彻底的B细胞清除,有助于迅速控制异常免疫反应和炎症进程。然而,本研究发现B细胞重建与临床疗效之间并非简单的线性对应关系,外周B细胞的恢复并不意味着肾脏应答消失。例5第6个月出现B细胞重建但获得PRR,例4第9个出现B细胞重建且计数逐渐升高,但尿蛋白仍持续下降,肾功能稳定,并在第14个月达到PRR。NOBILITY试验表明,深度B细胞耗竭与CRR显著相关[16],且长期维持耗竭状态更有利于缓解的持续[21],这为临床上根据B细胞监测结果制定治疗间隔提供了理论依据。糖皮质激素暴露剂量与感染等不良事件的发生密切相关。既往研究表明,当泼尼松剂量超过40 mg/d或等效剂量[>0.6～0.7 mg/(kg·d)]时,严重感染和死亡的风险显著升高[21]。OBZ治疗可使LN患者糖皮质激素快速减量, REGENCY试验中42.7%的患者在第76周获得CRR且泼尼松剂量≤7.5 mg/d[13]。本研究中患者的泼尼松剂量在第9个月即减至7.5 mg/d,CRR率为37.5%,且未观察到严重感染,表明OBZ治疗有助于激素快速减量,且具有良好的耐受性与安全性。随访过程中,患者外周血IgG和CD4+ T淋巴细胞水平总体稳定,提示尽管OBZ治疗后B细胞耗竭,并未引起明显的体液免疫和细胞功能抑制。REGENCY试验中,排除新型冠状病毒相关感染后,OBZ治疗没有增加严重感染发生[13],但临床中仍需高度警惕感染并发症。本研究为单中心回顾性观察,样本量较小且随访时间相对较短,无法评估不同病理类型患者对OBZ的治疗反应。OBZ治疗LN的最佳给药时机、剂量疗程、合并用药及长期应用的安全性等问题仍需前瞻性、大样本、长期随访研究进一步验证。小结:采用OBZ治疗难治及复发性LN能快速获得临床和免疫学缓解,减少糖皮质激素用量,且能长期维持B细胞耗竭,无严重并发症,为难治及复发性LN提供新型有效的治疗方案。其疗效及安全性仍有待于在大规模前瞻性研究中进一步验证。参考文献 1 ALMAANI S, MEARA A, ROVIN B H. Update on lupus nephritis. Clin J Am Soc Nephrol, 2017, 12(5):825-835. 2 APPEL G B. Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol, 2009:1103-1112. 3 FURIE R, ROVIN B H, HOUSSIAU F, et al. Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med, 2020,383(12):1117-1128. 4 PARIKH S V, ROVIN B H. Current and Emerging Therapies for Lupus Nephritis. J Am Soc Nephrol, 2016,27(10):2929-2939. 5 EL HACHMI M, JADOUL M, LEFèBVRE C, et al. Relapses of lupus nephritis: incidence, risk factors, serology and impact on outcome. Lupus, 2003,12(9):692-696. 6 DOOLEY M A, JAYNE D, GINZLER E M, et al. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med, 2011,365(20):1886-1895. 7 ANDERS H J, SAXENA R, ZHAO M H, et al. Lupus nephritis. Nat Rev Dis Primers, 2020, 6(1):7. 8 ZHAO X, YANG S Q, LI M, et al. Effectiveness and safety of B cell-targeting biologics in the treatment of lupus nephritis: a systematic review and network meta-analysis. Ren Fail, 2024,46(2):2416605. 9 Kidney Disease: Improving Global Outcomes (KDIGO) Lupus Nephritis Work Group. KDIGO 2024 Clinical Practice Guideline for the Management of Lupus Nephritis. Kidney Int, 2024, 105(1 Suppl 1): S1-S69. 10 FANOURIAKIS A, KOSTOPOULOU M, ANDERS H J, et al. “EULAR recommendations for the management of systemic lupus erythematosus with kidney involvement: 2025 update.” Ann Rheum Dis,2025,Ootobev 16 (in Press):https://doi.org/10.1016/j.ard.2025.09.007 11 ROVIN B H, FURIE R, LATINIS K, et al. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum, 2012,64(4):1215-1226. 12 DABKOWSKA A, DOMKA K, FIRCZUK M. Advancements in cancer immunotherapies targeting CD20: from pioneering monoclonal antibodies to chimeric antigen receptor-modified T cells. Front Immunol, 2024,15:1363102. 13 FURIE R A, ROVIN B H, GARG J P, et al. Efficacy and safety of obinutuzumab in active lupus nephritis. N Engl J Med, 2025, 392(15): 1471-1483. 14 Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int Suppl, 2012, 2(2): 139-274. 15 陈樱花, 胡伟新, 刘志红. 执行摘要:中国狼疮肾炎诊治和管理指南(2025版). 肾脏病与透析肾移植杂志,2025,34(3):251-255. 16 FURIE R A, AROCA G, CASCINO M D, et al. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis, 2022,81(1):100-107. 17 LI X Q, LIU Y, CAI Z Y, et al. Obinutuzumab is Effective as an Initial Treatment for PLA2R-Associated Primary Membranous Nephropathy: A Retrospective, Single-Center Trial. Drug Des Devel Ther, 2025,19:5961-5972. 18 LI H, JIN L, XIE X, et al. Additive Obinutuzumab Achieves High Remission Rates in Rituximab-Refractory Membranous Nephropathy. Am J Nephrol, 2025:1-9. 19 SU W, LI J, MEN J, et al. Obinutuzumab is effective for the treatment of rituximab-refractory PLA2R-associated membranous nephropathy. Clin Kidney J, 2025,18(5):sfaf026. 20 陈独群, 涂远茂, 李辉,等. 奥妥珠单抗治疗难治及高危磷脂酶A2受体相关膜性肾病的疗效观察. 肾脏病与透析肾移植杂志,2025,34(1):1-7. 21 FIGUEROA-PARRA G, CUéLLAR-GUTIéRREZ M C, GONZáLEZ-TREVIO M, et al. Impact of Glucocorticoid Dose on Complete Response, Serious Infections, and Mortality During the Initial Therapy of Lupus Nephritis: A Systematic Review and Meta-Analysis of the Control Arms of Randomized Controlled Trials. Arthritis Rheumatol, 2024,76(9):1408-1418. ⓒ 本文版权归《肾脏病与透析肾移植杂志》编辑部所有【引用本文】张芮枫、王晶晶、汪欣悦、陈独群、涂远茂、章海涛. 奥妥珠单抗治疗难治及复发性狼疮肾炎的疗效观察[J]. 肾脏病与透析肾移植杂志, 2025, 34(6): 518-523. ZHANG Ruifeng, WANG Jingjing, WANG Xinyue, CHEN Duqun, TU Yuanmao, ZHANG Haitao. 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临床结果临床研究

2026-01-27

·BioSpace

Health Canada authorizes Gazyva® (obinutuzumab) for adults with active lupus nephritis

The approval introduces the first and only anti-CD20 monoclonal antibody shown to improve complete renal response in lupus nephritis, offering a new treatment option for patients and potentially delaying or preventing end-stage kidney disease. 1,2,3 MISSISSAUGA, ON , Jan. 26, 2026 /CNW/ - Hoffmann-La Roche Limited (Roche Canada) is pleased to announce that on January 22, 2026, Health Canada has approved Gazyva® (obinutuzumab) for the treatment of adult patients with active lupus nephritis who are receiving standard therapy. Following four initial doses in the first year, Gazyva can be administered twice yearly, offering an effective and potentially more convenient treatment option than traditional targeted therapies. 3 Health Canada authorizes Gazyva® (obinutuzumab) for adults with active lupus nephritis "Roche Canada is committed to bringing the best innovation in healthcare to Canadians when they need it most. This milestone for Gazyva is a testament to that vision," said Dr. Daniel Edgcumbe, Vice-President, Medical and Regulatory Affairs, Roche Canada. "For Canadians facing lupus nephritis, a disease with no current cure, this represents our ongoing commitment to providing new therapeutic options for lupus nephritis patients." In Canada, lupus affects approximately 1 in 1,000 people. 4 Among those with lupus, nearly 40% develop lupus nephritis, a kidney-specific form of systemic lupus erythematosus (SLE) 5 . SLE is a broader autoimmune disease that can affect various organs, such as the skin, joints, and blood system. Lupus nephritis occurs when the immune system mistakenly attacks the kidneys, potentially leading to impaired kidney function or even kidney failure. "Lupus nephritis is one of the most frequent, severe, and debilitating complications of systemic lupus erythematosus, and treatment options are unfortunately limited," said Dr. Ann Clarke, Professor in the Division of Rheumatology, Department of Medicine, Cumming School of Medicine, University of Calgary. "Health Canada's approval of Gazyva represents a significant advancement in lupus treatment, offering renewed hope to those living with lupus nephritis by improving kidney outcomes and long-term overall health." Health Canada's authorization of Gazyva is based on results from the Phase II NOBILITY and phase III REGENCY studies. In REGENCY, data showed that nearly half of the participants (46.4%) on Gazyva in combination with standard therapy achieved a complete renal response compared to 33.1% on standard therapy alone. That means that adding Gazyva to the current standard of care treatment was more effective than the standard of care treatment alone. Data showed a statistically significant and clinically meaningful increase in the proportion of patients who achieved complete renal response with reduced corticosteroid use and an improvement in proteinuric response, all signalling improved disease control. 2 The safety pro Gazyva was consistent with the well-characterised pro in its haematology-oncology indications. 3 "Lupus nephritis is a complex and unpredictable disease that places a significant burden on patients and families," said Leanne Mielczarek, CEO, Lupus Canada. "Ongoing symptoms and disease flares affect not only physical health but also mental well-being, work, and daily life. Gazyva represents an important new treatment option for Canadians living with lupus nephritis, and Health Canada's approval expands access to much-needed evidence-based therapies for patients and the clinicians who care for them." Roche Canada is committed to working with the provincial and territorial jurisdictions to make Gazyva available as soon as possible through public and private drug plans for the patients who need it. About Lupus Nephritis Lupus nephritis is a potentially life-threatening manifestation of systemic lupus erythematosus, an autoimmune disease that commonly affects the kidneys. 6 Lupus nephritis is characterised by an irreversible loss of nephrons, the filtering structures of the kidneys. Periods of intense disease activity, known as flares, can speed up the loss of nephrons and, if left unchecked, may lead to a progressive loss of kidney function. Even with the latest treatments, up to a third of people will progress to end-stage kidney disease, where dialysis or transplant are the only options and life expectancy and quality of life are substantially reduced. 7 Lupus nephritis affects more than 1.7 million people worldwide – predominantly women, mostly of colour and usually of childbearing age. 8 Currently, there is no cure. 6 About Gazyva Gazyva (obinutuzumab) is a Type II engineered humanised monoclonal antibody designed to attach to CD20, a protein found on certain types of B cells. 9 In lupus nephritis, disease-causing B cells drive persistent inflammation that damages the kidneys and reduces their ability to function properly. 10 Data suggests that Gazyva depletes disease-causing B cells, helping to limit further damage to the kidneys and potentially preventing or delaying progression to end-stage kidney disease. 2 Gazyva is approved for adults with lupus nephritis in Canada, the United States and European Union and in over 100 countries for various types of haematological cancers. About the REGENCY Study REGENCY [ NCT04221477 ] is a phase III, randomised, double-blind, placebo-controlled, multicentre study investigating the efficacy and safety of Gazyva (obinutuzumab) plus standard therapy (mycophenolate mofetil and glucocorticoids) in people with active/chronic International Society of Nephrology/Renal Pathology Society 2003 proliferative Class III or IV lupus nephritis, with or without Class V. The study enrolled 271 people, who were randomised 1:1 to receive either Gazyva plus standard therapy or placebo plus standard therapy. The study population was representative of the real-world population of people with lupus nephritis. About Roche Canada At Roche Canada, patients and science are at the heart of everything we do. Our passion for science and our commitment to relentlessly pursuing the impossible for patients have made us one of the world's leading pharmaceutical, in-vitro diagnostics, and diabetes care management companies. With our combined strength in diagnostics and pharmaceuticals, we're driving healthcare forward, while ensuring we deliver meaningful benefits for patients and a sustainable healthcare system. Because we're committed to making quality healthcare accessible to everyone. And we're adding our expertise in new areas, such as artificial intelligence, real world data collection and analysis and collaborating with many different sectors and industries. Having the courage to reinvent ourselves and question the status quo is what patients and the healthcare system expect from Roche – and our commitment is as strong today as it was on the first day of our Canadian journey in 1931. Today, Roche Canada employs almost 2,000 people across the country through its Pharmaceuticals division in Mississauga, Ontario as well as its Diagnostics division in Laval, Québec. For more information, please visit or follow Roche Canada on LinkedIn. All trademarks used or mentioned are the property of its respective owners. References 1. Furie RA, et al. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022 Jan;81(1):100-07. 2. Furie RA, et al. Efficacy and safety of obinutuzumab in active lupus nephritis. N Engl J Med. 2025 Feb;392:1471-83. 3. Gazyva Product Monograph, January 22, 2026 4. Lupus Canada; [cited 2026 January 7]. Available from: 5. Hanly JG,et al. The frequency and outcome of lupus nephritis: results from an international inception cohort study. Rheumatology (Oxford). 2016 Feb;55(2):252-62. 6. Hocaoglu M et al. Incidence, prevalence, and mortality of lupus nephritis: a population-based study over four decades using the Lupus Midwest Network. Arthritis & Rheumatol 2023 Apr;75(4):567-573. 7. Mok C, et al. Treatment of lupus nephritis: consensus evidence and perspectives. Nat Rev Rheumatol. 2023 Apr;19(4):227-38. 8. Anders HJ et al. Lupus nephritis. Nat Rev Dis Primers. 2020 Jan 23;6(1):7. 9. Herter S, et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models. Mol Cancer Ther. 2013 Oct;12(10):2031-42. 10. Atisha-Fregoso Y, et al. Meant to B: B cells as a therapeutic target in systemic lupus erythematosus. J Clin Investig. 2021 Jun 15;131(12):e149095. SOURCE Hoffmann-La Roche Limited (Roche Canada)

临床结果上市批准临床3期

100 项与奥妥珠单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09321	奥妥珠单抗	L01XC15	DB08935

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
狼疮性肾炎	美国	Genentech, Inc.	2025-10-17
CD20阳性B细胞慢性淋巴细胞白血病	日本	Chugai Pharmaceutical Co., Ltd.	2022-12-23
CD20阳性滤泡性淋巴瘤	日本	Nippon Shinyaku Co., Ltd.	2018-07-02
CD20阳性滤泡性淋巴瘤	日本	Chugai Pharmaceutical Co., Ltd.	2018-07-02
滤泡性淋巴瘤	澳大利亚	F. Hoffmann-La Roche Ltd.	2014-05-15
慢性淋巴细胞白血病	美国	Genentech, Inc.	2013-11-01

未上市

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适应症	最高研发状态	国家/地区	公司	日期
边缘区B细胞淋巴瘤	申请上市	中国	F. Hoffmann-La Roche Ltd.	2019-09-28
膜性肾小球肾炎	临床3期	荷兰	-	2025-10-01
肿瘤溶解综合征	临床3期	美国	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	澳大利亚	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	法国	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	希腊	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	塞尔维亚	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	西班牙	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	中国台湾	AbbVie, Inc.	2024-08-05
肿瘤溶解综合征	临床3期	英国	AbbVie, Inc.	2024-08-05

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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


NCT04608318 (CLL17, Pubmed \| N Engl J Med)	临床3期	慢性淋巴细胞白血病	909	Venetoclax-Obinutuzumab	艱衊簾簾膚築夢膚獵鏇(鏇簾選膚壓憲醖鏇艱觸) = 鹽範積齋齋遞構鏇製齋廠餘壓衊獵築夢網襯積 (製繭蓋襯襯醖鑰醖製構 ) 更多	非劣	2025-12-06
				Venetoclax-Ibrutinib	艱衊簾簾膚築夢膚獵鏇(鏇簾選膚壓憲醖鏇艱觸) = 選壓鑰襯願鹹醖廠顧齋廠餘壓衊獵築夢網襯積 (製繭蓋襯襯醖鑰醖製構 ) 更多
ASH2025	N/A	慢性淋巴细胞白血病一线	3,844	Second-generation BTKi	窪願艱艱艱糧積獵遞鹽(蓋選餘糧鹹蓋顧鏇願獵) = 鹹膚衊簾鑰鬱構鏇襯鹽網鑰憲構淵構糧廠衊願 (製觸獵壓鬱顧鑰築鹽顧 )	积极	2025-12-06
				V+O	窪願艱艱艱糧積獵遞鹽(蓋選餘糧鹹蓋顧鏇願獵) = 衊淵鹹遞壓鏇衊鏇範鏇網鑰憲構淵構糧廠衊願 (製觸獵壓鬱顧鑰築鹽顧 )
ASH2025	N/A	慢性淋巴细胞白血病 \| 小淋巴细胞淋巴瘤一线	154	Venetoclax-obinutuzumab	淵襯鹽製範鹹獵築壓鏇(齋淵鬱構廠鹹衊糧鑰鹹) = 網膚範淵獵憲網鹹製鑰餘觸糧襯糧齋鏇範獵齋 (繭鏇鑰蓋憲淵艱齋構衊, 86 ~ 96) 更多	积极	2025-12-06
				Venetoclax-obinutuzumab (frontline)	淵襯鹽製範鹹獵築壓鏇(齋淵鬱構廠鹹衊糧鑰鹹) = 獵築廠糧繭選憲顧網製餘觸糧襯糧齋鏇範獵齋 (繭鏇鑰蓋憲淵艱齋構衊, 91 ~ 100) 更多
NCT05783596 (GLOBIN, ASH2025)	临床2期	滤泡性淋巴瘤一线	35	Glofitamab+obinutuzumab	窪憲遞遞廠夢構獵淵齋(餘遞觸積鏇廠網鬱鏇壓) = 鹽襯願醖願齋糧蓋獵願餘顧鹹獵憲齋鏇夢鬱糧 (齋壓觸鹽製衊窪築簾夢, 73 ~ 97) 更多	积极	2025-12-06
ICLL-07 (ASH2025)	临床2期	慢性淋巴细胞白血病一线	135	Ibrutinib 420 mg/day	築鹹簾糧獵鬱窪觸範繭(顧範艱憲網網艱醖膚艱) = Twelve patients died, including 2 from cardiac toxicity during treatment with O+I attributable to I (M6 and M7). The ten other deaths are distributed among 4 infections (3 bacterial pneumonias at M38, M55, M50 and 1 COVID 19 at M49), 1 histiocytic sarcoma (M47), 1 myelodysplasia (MDS; M56) and 1 acute myeloid leukemia (AML; M68). Three deaths were due to progression (n=1, M103) or transformation in Richter large B-cel lymphoma (n=1; M54) or Hodgkin lymphoma (n=1; M23). 簾構觸築積顧衊構蓋構 (糧鬱網製製艱鑰選遞淵 ) 更多	积极	2025-12-06
ASH2025	N/A	慢性淋巴细胞白血病 \| 小淋巴细胞淋巴瘤	45	Zanubrutinib+venetoclax	範選淵鬱構鹹網範鏇艱(廠顧窪醖選網廠顧窪觸) = The most common any grade AE that occurred in 20% or more pts were fatigue (56%), diarrhea (53%), hypertension (31%), nausea (27%), upper respiratory infection (27%), arthralgia (27%), bruising (24%), neutropenia (22%), thrombocytopenia (22%), and rash (20%). No atrial fibrillation was recorded. 選鹹獵選顧選選醖鬱鹹 (糧壓獵顧廠襯觸鹹鹹蓋 ) 更多	积极	2025-12-06
NCT03332017 (ROSEWOOD, ASH2025)	临床2期	滤泡性淋巴瘤	214	zanubrutinib + obinutuzumab	壓鑰醖製餘選鹹鬱夢艱(膚顧憲襯觸艱製廠鏇窪) = 艱醖夢遞顧構範顧膚憲夢蓋衊淵憲顧艱顧壓顧 (壓簾繭廠艱壓網鏇鹹鏇 ) 更多	积极	2025-12-06
				obinutuzumab	壓鑰醖製餘選鹹鬱夢艱(膚顧憲襯觸艱製廠鏇窪) = 廠鏇鏇鏇積鏇夢鏇構鹽夢蓋衊淵憲顧艱顧壓顧 (壓簾繭廠艱壓網鏇鹹鏇 ) 更多
CICERO (ASH2025)	N/A	慢性淋巴细胞白血病	45	Acalabrutinib +/- Obinutuzumab	淵鏇醖鏇夢範願夢獵艱(蓋觸構醖淵襯夢遞鹹膚) = 鑰襯艱衊餘齋窪膚顧製鑰選醖簾鏇選鬱憲範壓 (網鹽願繭獵繭壓艱糧鹽 ) 更多	积极	2025-12-06
NCT04169737 (ASH2025)	临床2期	慢性淋巴细胞白血病	84	AcalabrutinibObinutuzumabVenetoclax + Obinutuzumab (early Obinutuzumab)	顧襯醖願鏇蓋觸蓋網鏇(鹹淵願願艱範範齋選憲) = Grade ≥3 infections (p=0.013) and neutropenia (p<0.00001) were significantly higher in the 1st Y in the AV + early O arm. 築願簾範蓋鏇願構艱醖 (齋夢製構願鬱構齋積膚 ) 更多	积极	2025-12-06
				Acalabrutinib + VenetoclaxObinutuzumab (AV without early O with possible late Obinutuzumab)
NCT04277637 (BGB-11417-101, ASH2025)	临床1期	慢性淋巴细胞白血病 \| 小淋巴细胞淋巴瘤一线	15	Zanubrutinib + Obinutuzumab + Sonrotoclax 320mg	醖憲鹽襯鏇衊鬱醖淵製(鑰觸鏇廠築鹹糧淵醖顧) = 33% 鏇構廠糧獵觸選夢衊願 (夢膚餘鏇夢醖鬱顧蓋顧 ) 更多	积极	2025-12-06