An Open-label, Multicenter Study to Assess the Effect of Zigakibart Treatment on Histologic, Circulating, and Excreted Markers of Kidney Disease and Dysfunction in Adult Patients With IgA Nephropathy.

The purpose of the study is to assess the effect of zigakibart on IgA nephropathy (IgAN) disease progression.

开始日期2026-03-26

申办/合作机构

Novartis Pharmaceuticals Canada, Inc.

NCT06858319

/ Recruiting临床3期

A Multicenter Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Zigakibart in Adults With Primary IgA Nephropathy.

The purpose of this study is to determine if zigakibart is safe and effective for long-term use in patients with immunoglobulin A nephropathy (IgAN). This is an extension study for patients who have already completed an another zigakibart study.

开始日期2025-07-28

申办/合作机构

Novartis Pharmaceuticals Canada, Inc.

ChiCTR2500096892

/ Recruiting临床3期IIT

A Phase 3, Randomized, Double-blind, Placebo-controlled Study of BION-1301 in Adults with IgA Nephropathy(The BEYOND Study)

开始日期2024-09-25

申办/合作机构-

100 项与泽戈奇拜单抗相关的临床结果

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100 项与泽戈奇拜单抗相关的转化医学

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100 项与泽戈奇拜单抗相关的专利（医药）

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项与泽戈奇拜单抗相关的文献（医药）

2026-06-01·Kidney International Reports

Zigakibart Potently Inhibits A Proliferation-Inducing Ligand-Mediated IgA Production, Addressing IgAN Pathogenesis Root Causes

Article

作者: Bakker, Jeroen ; Kreijtz, Joost ; van Eenennaam, Hans ; van Zandvoort, Peter ; Van Elsas, Andrea ; Dulos, John ; Kuo, Jay J ; Warncke, Max ; Cotton, Victoria ; Medema, Jan Paul ; Guadagnoli, Marco ; Barratt, Jonathan ; Jansen, Wout ; Driessen, Lilian ; Vink, Paul ; Lo, Jeannette

Introduction:

Zigakibart is a humanized IgG4 monoclonal antibody (mAb) binding A proliferation-inducing ligand (APRIL, TNFSF13), a critical factor in IgA nephropathy (IgAN) pathogenesis. Results from the ongoing phase 1/2 ADU-CL-19 study (NCT03945318) have shown clinically meaningful outcomes in patients with IgAN treated with zigakibart.

Methods:

We conducted a preclinical characterization of zigakibart using in vitro methods, including investigation of its binding to APRIL from various species, blocking of APRIL binding to transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B-cell maturation antigen (BCMA), investigation of the potency of zigakibart on BCMA- and TACI-reporter cells, and the assessment of the effect of APRIL blockade on human plasma cell survival and Ig production. In vivo methods were used to characterize zigakibart in human APRIL transgenic mice (hAPRIL-tg) and nonhuman primates.

Results:

Zigakibart potently blocked APRIL binding to TACI and BCMA and inhibited human plasma cell survival, which are key mediators in IgAN pathogenesis. Zigakibart selectively reduced circulating IgA and IgM to a greater extent than IgG and inhibited T-cell-independent antibody responses and IgA deposition in the kidney in vivo. Importantly, zigakibart inhibited IgA+ and IgM+ to a greater extent than IgG+ human plasma cells in vitro.

Conclusion:

In these preclinical studies, zigakibart demonstrated robust pharmacological activity and, by neutralizing APRIL, inhibited markers associated with the pathogenesis of IgAN. Zigakibart therefore provides a potentially disease-modifying approach for IgAN treatment. Evaluation of the effects of zigakibart on proteinuria and long-term kidney function in adults with IgAN is ongoing in the ADU-CL-19 study and the phase 3 BEYOND study (NCT05852938).

2025-09-01·KIDNEY INTERNATIONAL

Zigakibart demonstrates clinical safety and efficacy in a Phase 1/2 trial of healthy volunteers and patients with IgA nephropathy

Article

作者: Kooienga, Laura ; Dulos, John ; Agha, Irfan ; Smith, William ; van Eenennaam, Hans ; Song, Yuanbo ; Van Elsas, Andrea ; Lo, Jeannette ; Kim, Sung Gyun ; Barratt, Jonathan ; Lee, Eun Young ; Thomas, Hannah ; Workeneh, Biruh

INTRODUCTION:

Zigakibart is a humanized IgG4 monoclonal antibody that binds the cytokine A Proliferation-Inducing Ligand (APRIL, also known as TNFSF13). APRIL is a critical factor in immunoglobulin (Ig) A nephropathy (IgAN) pathogenesis.

METHODS:

Here, we report healthy volunteers (63 overall) and 100-week data from an ongoing Phase 1/2 clinical trial in 40 patients with IgAN (NCT03945318) treated with zigakibart.

RESULTS:

In healthy volunteers, zigakibart was well tolerated following intravenous administration of single doses ranging from 10-1350 mg or multiple doses ranging from 50-450 mg every two weeks. Zigakibart exposure increased in a dose-proportional manner, with corresponding durable reductions in levels of free APRIL, IgA and IgM, and to a lesser extent, IgG. In patients with IgAN, zigakibart 600 mg, administered subcutaneously every two weeks, was well tolerated with no treatment-emergent adverse events leading to study drug discontinuation or death. A 60% reduction in proteinuria and sustained estimated glomerular filtration rate stabilization were observed at week 100. There was a notable decrease in hematuria, as well as rapid and durable reductions in IgA, galactose-deficient IgA (Gd-IgA1), and IgM levels, with a modest reduction in IgG.

CONCLUSIONS:

Overall, zigakibart demonstrated robust pharmacological activity, and clinical evidence shows an acceptable safety profile with clinically meaningful proteinuria reduction and sustained estimated glomerular filtration rate stabilization in patients with IgAN, providing a potentially disease-modifying approach for the treatment of IgAN. The effects of zigakibart on proteinuria and long-term kidney function in adults with IgAN are being evaluated in the ongoing phase 3 BEYOND study (NCT05852938).

2023-12-01·Clinical rheumatology

A narrative review of potential drug treatments for nephritis in children with IgA vasculitis (HSP)

Review

作者: Lamond, Megan ; Marro, Julien ; Chetwynd, Andrew J ; Oni, Louise ; Williams, Chloe E C

Abstract:

Immunoglobulin A (IgA) vasculitis (IgAV, also known as Henoch-Schoenlein purpura, HSP) is the most common vasculitis of childhood. It usually presents with a simple, self-limiting disease course; however, a small subset of patients may develop kidney involvement (IgAV-N) which occurs 4–12 weeks after disease onset and is the biggest contributor to long-term morbidity. Treatment currently targets patients with established kidney involvement; however; there is a desire to work towards early prevention of inflammation during the window of opportunity between disease presentation and onset of significant nephritis. There are no clinical trials evaluating drugs which may prevent or halt the progression of nephritis in children with IgAV apart from the early use of corticosteroids which have no benefit. This article summarises the latest scientific evidence and clinical trials that support potential therapeutic targets for IgAV-N that are currently being developed based on the evolving understanding of the pathophysiology of IgAV-N. These span the mucosal immunity, B-cell and T-cell modulation, RAAS inhibition, and regulation of complement pathways, amongst others. Novel drugs that may be considered for use in early nephritis include TRF-budesonide; B-cell inhibiting agents including belimumab, telitacicept, blisibimod, VIS649, and BION-1301; B-cell depleting agents such as rituximab, ofatumumab, and bortezomib; sparsentan; angiotensin converting enzyme inhibitors (ACE-Is); and complement pathway inhibitors including avacopan, iptacopan, and narsoplimab. Further clinical trials, as well as pre-clinical scientific studies, are needed to identify mechanistic pathways as there may be an opportunity to prevent nephritis in this condition.Key Points• Kidney involvement is the main cause of long-term morbidity and mortality in IgA vasculitis despite the current treatment recommendations.• The evolving understanding of the pathophysiology of IgA vasculitis is allowing exploration of novel treatment options which target underlying immune pathways.• Novel treatments currently being trialled in IgA nephropathy may have benefit in IgA vasculitis due to the similarities in the underlying pathophysiology, such as TRF-budesonide, B-cell modulators, and complement inhibitors.• Further studies, including clinical trials of novel drugs, are urgently needed to improve the long-term outcomes for children with IgA vasculitis nephritis.

267

项与泽戈奇拜单抗相关的新闻（医药）

2026-06-05

·allsci.com

Otsuka’s Voyxact on course for full approval in IgA nephropathy after positive Phase III

Twelve-month eGFR data from the Phase III VISIONARY trial of sibeprenlimab (Voyxact) in IgA nephropathy show that Otsuka’s anti-APRIL monoclonal antibody stabilized kidney function compared to placebo. The result is likely to support sibeprenlimab‘s conversion of its existing accelerated approval based on proteinuria reduction, since demonstrating eGFR preservation is the confirmatory evidence needed for full FDA approval in IgA nephropathy. The pre-specified interim analysis enrolled 320 adults with primary IgAN at risk of disease progression. At 12 months, sibeprenlimab-treated patients showed a mean eGFR change from baseline of +0.7 mL/min/1.73 m² (95% CI, –0.9 to 2.3), compared with –4.8 mL/min/1.73 m² (95% CI, –6.3 to –3.3) in the placebo arm — a treatment effect of 5.5 mL/min/1.73 m² (95% CI, 3.4 to 7.6). The annualized eGFR slope showed –3.0 mL/min/1.73 m²/year with sibeprenlimab versus –7.6 mL/min/1.73 m²/year with placebo, a treatment effect of 4.6 mL/min/1.73 m²/year. The sibeprenlimab eGFR change from baseline met the KDIGO treatment goal of limiting annual kidney function decline to below 1 mL/min/1.73 m²/year. Safety was consistent with prior data; infections (49% vs. 45%) and injection site reactions (24% vs. 23%) were the most common adverse events, with the majority mild or moderate. Otsuka has initiated a rolling supplemental Biologics License Application (sBLA) submission to the US FDA for traditional approval based on the 24-month eGFR endpoint data, which remain pending. Sibeprenlimab selectively inhibits APRIL, blocking upstream B-cell-driven production of pathogenic galactose-deficient IgA1 without depleting B cells. The IgAN landscape now includes multiple approved agents with distinct mechanisms: Novartis’ Fabhalta (iptacopan), an oral complement factor B inhibitor, reported a 49.3% slowing of eGFR slope decline over two years in the APPLAUSE-IgAN Phase III trial and has a priority review filing pending traditional approval; Vera Therapeutics’ atacicept, a dual BAFF/APRIL inhibitor, has a PDUFA date of July 7, 2026 for accelerated approval. Vertex Pharmaceuticals’ povetacicept, a dual BAFF/APRIL TACI-Fc fusion protein, also has a BLA under rolling review. Cross-trial comparisons are limited by differences in patient populations, background therapy, and follow-up duration. The VISIONARY 24-month final analysis, which serves as the primary confirmatory endpoint for Otsuka’s traditional approval submission, will be the next key data readout. This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/ Your email address will not be published. Required fields are marked * Comment * Name * Email * Website Privacy Terms About Us Copyright © 2026. AllSci Corp. All rights reserved.

临床3期临床结果优先审批加速审批上市批准

2026-06-04

·自免药研社

自免肾病第一大病 IgAN：溯源、病程、靶点与全球新药研发全盘点

自免肾病临床缺口凸显：云顶新耀 (1952.HK) 与 Travere (TVTX) 落地 EVER001 全球权益出海合作一、IgA 肾病（Immunoglobulin A Nephropathy，IgAN） 1. 疾病溯源与流行病学由来：1968 年法国病理学家 Jean Berger 凭借肾活检免疫荧光特征，首次发现肾小球系膜区 IgA 优势沉积的特殊肾炎，命名Berger 病；1970 年后全球统一标准学名：IgA 肾病（Immunoglobulin A Nephropathy，IgAN）。流行病学特征：全球高发原发性肾小球肾炎，亚洲患病率领先，我国占全部原发性肾小球肾炎 40%~45%，欧美人群发病率偏低；高发人群集中在 15～40 岁青壮年，男性发病占比更高；全球年新发约 25/100 万人口，未经规范干预下，30% 左右患者在 10～20 年病程中进展至终末期肾病（ESRD），是中青年尿毒症首位原发肾病诱因。发病诱因：\\ 遗传易感缺陷 + 呼吸道 / 肠道黏膜免疫紊乱 + 环境刺激（反复感染、肠道菌群紊乱、外源致敏饮食）\\ 三大要素协同触发自身免疫异常。 2. 分类 •原发性 IgAN：遗传易感人群黏膜相关淋巴组织（MALT）稳态失衡，B 细胞异常合成半乳糖缺陷型 IgA1（Gd-IgA1，内源性自身抗原），机体针对性生成抗 Gd-IgA1 自身抗体，二者形成循环致病性免疫复合物，特异性沉积于肾小球系膜区，激活补体与局部炎症反应，以系膜增生为核心病理损伤的器官特异性自身免疫性肾小球病；确诊金标准：肾活检免疫荧光提示肾小球系膜区 IgA 为主的免疫复合物沉积，可伴少量 IgG/IgM 共沉积。 •继发性 IgAN：继发于过敏性紫癜、系统性红斑狼疮、银屑病、强直性脊柱炎等全身性自身免疫病，属于系统性自身免疫病累及肾脏的靶器官并发症。二、疾病发展过程阶段 1：隐匿前驱期（HIT0，肠肾轴前置损伤）先天携带 C1GALT1、ST6GALNAC2 等糖基化酶易感基因突变人群，受扁桃体慢性炎症、肠道菌群失调、反复呼吸道 / 消化道感染影响，肠道派尔集合淋巴结（Peyer 结）B 细胞生理调控紊乱，为后续异常 Gd-IgA1 大量合成奠定病理基础（2025 年国际肾病学会在经典四重打击基础上新增 HIT0 前置环节）。阶段 2：无症状免疫启动期黏膜 B 细胞在促炎因子刺激下大量合成 Gd-IgA1（HIT1），机体免疫系统将自身异常 IgA1 识别为异物，诱导 IgG/IgA 型自身抗体产生（HIT2），外周血形成微量免疫复合物；尿常规无异常、无任何临床症状，仅血清 Gd-IgA1 指标升高。阶段 3：急性临床发作期上呼吸道 / 消化道感染后 1～3 天，体内大量免疫复合物组装完成（HIT3）并靶向定植肾小球系膜（HIT4），典型临床表现为一过性发作性肉眼血尿，多数患者残留持续性镜下血尿，可伴随轻度蛋白尿；感染诱发血尿是 IgAN 标志性临床特征。阶段 4：慢性进展期（数年至数十年慢性迁延）免疫复合物反复沉积持续激活系膜炎症与补体旁路通路，病理演变顺序：系膜细胞增殖→系膜基质蓄积→肾小球节段硬化→肾小管萎缩 + 肾间质纤维化；临床逐步出现持续性蛋白尿（UPCR＞0.5g/g 为肾病进展高危阈值，KDIGO2025）、难治性高血压、估算肾小球滤过率（eGFR）进行性下降。阶段 5：终末期肾病（ESRD）大量肾单位不可逆毁损、肾小球广泛全球硬化，进展为尿毒症，依赖长期透析或肾移植替代治疗；临床数据显示约 25%～30% 确诊 IgAN 患者远期步入该阶段。三、核心自身免疫致病机制：HIT0 前置 + 经典四重打击学说 HIT0：肠 - 肾轴源头损伤（发病始动环节）肠道菌群失衡、TLR 模式识别受体过度活化、扁桃体持续性慢性炎症，造成 MALT 内 B 细胞转录调控异常，糖基化酶C1GALT1 表达下调、ST6GALNAC2 上调，IgA1 分子铰链区 O - 糖基化缺失，生成异常 Gd-IgA1 自身抗原，构成全病程自免损伤起源。 HIT1（第一重打击）：致病性自身抗原异常合成 BAFF、APRIL 细胞因子持续刺激黏膜 B 细胞，诱导 B 细胞大量分化增殖，过量合成 Gd-IgA1；该分子因糖链缺失暴露全新抗原表位，成为 IgAN 特征性自体抗原。 HIT2（第二重打击）：机体产生特异性自身抗体机体免疫系统针对自体 Gd-IgA1 产生 IgG/IgA 亚型自身抗体，是 IgAN 典型自身免疫特征（自身抗原诱导自身抗体生成），也是 III 型超敏反应的分子基础。 HIT3（第三重打击）：致病性循环免疫复合物生成 Gd-IgA1 与抗 Gd-IgA1 自身抗体在血液循环中组装＞700kDa 大分子免疫复合物，复合物结合 sCD89、CD71 受体获得肾脏靶向亲和力，具备肾小球系膜定植能力。 HIT4（第四重打击）：肾小球局部免疫损伤 1.免疫复合物锚定肾小球系膜区； 2.异常激活补体旁路途径、凝集素途径（B 因子、C3、MASP 为关键靶点），释放补体源性促炎毒素； 3.系膜细胞活化增殖，大量分泌 TNF-α、IL-6 等促炎因子，足细胞受损、肾小球滤过屏障破损，诱发蛋白尿； 4.慢性持续性炎症逐级诱导肾小球硬化、肾小管间质纤维化，肾功能进行性丢失。补充遗传背景：全基因组关联研究（GWAS）证实 IGAN1~IGAN6 多个疾病易感位点，分别调控 B 细胞糖基化修饰、补体活化、黏膜免疫应答，决定个体 IgAN 发病遗传易感性。四、IgAN 靶向药物靶点汇总靶点大类对应致病环节靶点分子开发机理黏膜靶向糖皮质激素 HIT0/HIT1（抑制肠道 B 细胞）肠道糖皮质激素受体回肠局部缓释，抑制派尔淋巴结 B 细胞增殖，源头减少 Gd-IgA1 合成 BAFF/APRIL 通路 HIT1（B 细胞活化） BAFF、APRIL、TACI、BCMA 阻断细胞因子，抑制 B 细胞分化、IgA 类别转换，下调 Gd-IgA1 与自身抗体生成（IgAN 源头自免靶点，当前管线最热） BTK/JAK 激酶 HIT1/B 细胞胞内信号 BTK、JAK1/2 抑制 B 细胞胞内活化信号，减少致病性 IgA 合成补体通路 HIT4（肾脏局部损伤） B 因子、C3、C5、MASP 阻断补体旁路 / 凝集素通路活化，抑制系膜局部补体介导炎症损伤内皮素 / AT1 双受体 HIT4（肾小球纤维化、血流损伤） ETAR、AT1 改善肾小球高滤过、抑制系膜纤维化，非直接免疫抑制、靶器官保护 CD89/CD71 受体 HIT3（免疫复合物沉积） sCD89、CD71 阻断免疫复合物与系膜细胞结合，阻止复合物肾脏定植（临床前阶段为主） SGLT2 辅助进展管控 SGLT2 肾脏代谢保护、抗纤维化，基础治疗辅助靶点五、全球已上市 IgAN 靶向药物类别 1：肠道局部靶向糖皮质激素（作用 HIT0/HIT1，源头控抗原）布地奈德肠溶缓释胶囊（Nefecon/Tarpeyo，国内商品名：耐赋康）原研：Calliditas Therapeutics，国内商业化权益：云顶新耀；FDA：2021 加速批准、2023 全适应症获批；NMPA：2022 年国内获批上市。作用机制：pH 依赖性肠溶剂型，精准在回肠末端释放药物，靶向肠道 Peyer 结 B 淋巴细胞，从源头降低 Gd-IgA1 生成；肠道局部高浓度、全身激素暴露极低，规避传统全身激素不良反应。适应症：肾活检确诊、存在疾病进展风险的成人 IgAN（基线 UPCR≥1g/g）。类别 2：抗 APRIL 单克隆抗体（生物制剂，阻断 HIT1 B 细胞异常活化） Sibeprenlimab（斯贝利单抗，Voyxact，大冢 / Visterra） FDA：2025.11 全球首个 APRIL 单抗获批 IgAN 适应症；NMPA：2025 年 7 月递交 BLA 并纳入优先审评，预计 2026 年国内获批上市。机制：全人源抗 APRIL 单抗，阻断 APRIL-TACI/BCMA 信号通路，抑制 B 细胞 IgA 类别转换，临床数据证实血清 Gd-IgA1 降幅＞45%，尿蛋白（UPCR）平均下降 47%；给药方案：每月静脉输注 1 次。类别 3：口服补体 B 因子小分子抑制剂（靶向 HIT4 肾脏局部补体损伤） Iptacopan（伊普可泮，Fabhalta，诺华） FDA：2024.8 加速获批 IgAN；NMPA：2025 年国内获批 IgAN 适应症；2026 年 NEJM 刊发 APPLAUSE-IgAN 两年 III 期长期数据：可使 IgAN 患者肾功能年下降风险降低 49.3%，是全球首个经大型 III 期证实可延缓 eGFR 衰退的补体靶向口服药。机制：选择性抑制补体 B 因子，特异性阻断异常活化的补体旁路通路，减轻肾小球系膜区补体介导炎症损伤，每日口服给药。类别 4：内皮素受体拮抗剂（靶器官保护、抗纤维化，HIT4） 1.Sparsentan（司帕生坦，Filspari，Travere/BMS）：FDA2023 加速获批，NMPA 国内申报阶段；ETAR+AT1 双重拮抗，强效降尿蛋白、抑制肾小球间质纤维化，无全身性免疫抑制副作用。 2.Atrasentan（阿曲生坦，Vanrafia，诺华）：FDA2025 新增 IgAN 适应症，选择性 ETAR 拮抗剂，改善肾小球高滤过状态、延缓肾间质纤维化，每日口服。类别 5：传统基础治疗药物（KDIGO 指南一线通用方案） 1.RAS 抑制剂（ACEI/ARB：贝那普利、缬沙坦等）：KDIGO 指南基石用药，全病程管控血压、减少尿蛋白； 2.SGLT2 抑制剂（达格列净、恩格列净）：2025 版 KDIGO 正式纳入 IgAN 标准辅助用药，肾脏靶向保护、抑制肾纤维化； 3.全身糖皮质激素、吗替麦考酚酯：仅用于高进展风险患者短期选择性治疗，广谱非特异性免疫抑制，非精准靶向药。六、全球 IgAN 在研新药管线（一）NDA/BLA 申报阶段（审评中，近 1~2 年有望获批） 1.Atacicept（BAFF/APRIL 双靶点融合蛋白，Vera Therapeutics）：获 FDA 突破性疗法认定；III 期 ORIGIN 研究 2025 年完成入组并公布阳性顶线结果，2025 年末递交 FDA BLA，国内同步申报；同时阻断 BAFF、APRIL 双通路，抑制 B 细胞活化与抗 Gd-IgA1 自身抗体生成。 2.Zigakibart（抗 APRIL 单抗，诺华，原 Chinook）：关键性 III 期注册临床收尾，规划 2026 年中美同步申报；II 期临床 Gd-IgA1 最大降幅 74.4%，数据优于已上市 Sibeprenlimab。（二）III 期关键性注册临床（3 年内大概率递交上市申请） 1.Ravulizumab（长效 C5 单抗，阿斯利康 Ultomiris）：全球多中心 ICAN III 期研究，靶向补体终末通路 C5，阻断膜攻击复合物 MAC 形成，每 8 周静脉给药； 2.Iptacopan 常规全适应症：诺华 2026 年向 FDA 递交正式全适应症批准申请，补充 2 年长期肾功能终点数据； 3.多款口服 BTK 抑制剂（GS-4059、ARQ531）：全球同步 III 期，靶向 B 细胞胞内 BTK 信号，下调致病性 IgA 合成。（三）II 期临床（概念验证成功，剂量扩展研究阶段） 1.JAK 选择性抑制剂（GSK、荣昌生物 JAK1/2 抑制剂）：II 期临床可显著下调血清 Gd-IgA1，尿蛋白降幅 35%~42%； 2.口服 C3 补体抑制剂（Pegcetacoplan 口服剂型）：II 期探索 IgAN 适应症，同时阻断补体旁路、凝集素双通路； 3.肠肾轴益生菌 / 后生元制剂：II 期探索肠道菌群调控，通过改善肠道微生态间接减少黏膜异常 IgA 分泌。（四）I 期 / 临床前（分子验证、动物药效阶段） 1.抗 CD89/CD71 单克隆抗体：阻断免疫复合物与系膜细胞结合，动物模型显著减少肾小球 IgA 沉积； 2.Gd-IgA1 特异性中和抗体：直接靶向清除循环中致病性自身抗原 Gd-IgA1，目前进入 I 期人体试验； 3.C1GALT1 糖基化酶激动剂：修复 B 细胞糖基化先天缺陷，从源头纠正异常 Gd-IgA1 生成，处于临床前分子筛选。管线信息：本文全部临床数据、药品获批信息、管线进度均来源于 FDA 药品数据库、NMPA 审评公示、KDIGO 临床指南及药企官网公开临床试验结果。参考文献 [1] Wyatt RJ, Julian BA. IgA nephropathy. N Engl J Med, 2013;368 (25):2402-2414[2] Lafayette RA, et al. Iptacopan for IgA Nephropathy over 2 Years. N Engl J Med, 2026;394 (13):1229-1240[3] Wyatt RJ, et al. Pathogenesis of IgA nephropathy: update on multi-hit hypothesis. Kidney Int, 2024;105 (3):521-534[4] Park SJ, et al. Sibeprenlimab in Immunoglobulin A Nephropathy. N Engl J Med, 2025;393 (19):1819-1831 [5] Wyatt RJ, Novak J. Galactose-deficient IgA1 as autoantigen in IgAN: an update. Semin Nephrol,2023;43 (4):151389[6] Floege J, et al. Atacicept for IgA nephropathy: Phase3 ORIGIN topline analysis. J Am Soc Nephrol,2025;36 (9):1987-2001 [7] 中华医学会肾脏病学分会. IgA 肾病诊治指南（2024 修订版）, 中华肾脏病杂志，2025,41 (2):171-189 [8] 王菲菲，李冰. IgA 肾病发病机制研究进展，临床肾脏病杂志，2024,24 (11):938-943 免责声明：本文仅作信息分享，不代表自免药研社立场和观点，也不作治疗方案推荐和介绍，仅作学术研究参考，不构成任何临床应用建议。如有需求，请咨询和联系正规医疗机构。任何人依据本文内容作出决策而产生的相关风险，由行为人自行承担。

2026-06-04

·BioSpace

Novartis IgAN data in The Lancet show clinically meaningful slowing of kidney function decline with Vanrafia® over 2.5 years

Phase III ALIGN study results showed reduced rate of kidney function decline by ~34% with Vanrafia vs placebo, based on supportive eGFR slope analysis 1 Vanrafia reduced protein in urine by 38.3% vs placebo at 9 months, with reductions sustained through end of treatment 1 ,2 Patients additionally receiving background SGLT2 inhibitors also consistently showed slower kidney function decline with Vanrafia vs placebo 1 ,2 Basel, June 4, 2026 – Novartis reported final 2.5-year Phase III ALIGN results showing slower kidney function decline with Vanrafia ® (atrasentan) versus placebo in adults with IgA nephropathy (IgAN) 1 ,2 . Results were published in The Lancet and presented at the European Renal Association (ERA) Congress. Estimated glomerular filtration rate (eGFR) change from baseline favored Vanrafia, alongside sustained reductions of protein in the urine through end of treatment. Benefits were consistent across different measures of kidney function and in patients additionally receiving sodium-glucose co-transporter-2 (SGLT2) inhibitors 1,2 . “These results provide robust evidence of clinically meaningful slowing of kidney function decline over more than two years of treatment, reinforcing findings from the earlier analysis of proteinuria reduction,” said Richard Lafayette, MD, FACP, Professor of Medicine, Nephrology, Director of the Glomerular Disease Center at Stanford University Medical Center, and ALIGN Study Investigator and Steering Committee Member. “They highlight the role of a highly selective endothelin A receptor antagonist as part of an evolving treatment approach for IgAN.” Key efficacy results 1 ,2 Endpoint Vanrafia Placebo Effect vs placebo Main cohort Change from baseline in eGFR at end of study * (Week 136) -7.5 -9.9 2.4 (p=0.057) Change from baseline in eGFR at end of treatment (Week 132) -6.9 -9.5 2.6 (p=0.039) Annualized total eGFR slope (Weeks 0-136) -2.7 -4.1 1.4 (~34% slower decline; p=0.003) Change from baseline in urine protein-to-creatinine ratio (UPCR) at 9 months (Week 36 ) † -39.5% -1.9% 38.3% relative reduction Change from baseline in UPCR at end of treatment (Week 132 ) † -28.8% -0.6% 28.4% relative reduction SGLT2 inhibitor cohort Change from baseline in eGFR at end of study * (Week 136) -1.5 -10.6 9.1 (p=0.004) * Week 132 plus a 4-week off - treatment follow-up † UPCR at Week 36 assessed using 24-hour urine collection ; UPCR at Week 132 assessed using first - morning void samples . All p values are nominal except for the change from baseline in eGFR at the end of study in the main cohort ; all p values are two-sided ; eGFR change from baseline is expressed in mL/min/1.73 m²; annualized eGFR slope is expressed in mL/min/1.73 m²/year “ALIGN reinforces Vanrafia’s potential as a foundational IgAN therapy and our commitment to advancing long-term kidney protection through continued innovation,” said Ruchira Glaser, MD, MS, Global Head, Cardiovascular, Renal and Metabolic Development, Novartis. “Together with our broader portfolio, these data strengthen confidence in an evidence-based approach to managing this progressive disease.” Safety was consistent with prior studies, with adverse events similar to placebo and no new signals observed 1- 4 . Vanrafia received accelerated approval in the U.S. and China for reduction of proteinuria in adults with IgAN in 2025 5 , 6 . Novartis intends to use these data to support submission for traditional approval in 2026. About IgAN IgAN is a progressive autoimmune kidney disease, with approximately 25 people per million worldwide newly diagnosed each year 7 ,8 . IgAN is highly debilitating as it leads to inflammation in the small filters of the kidneys, excess protein in urine, and a gradual decline in eGFR 9 . Up to 50% of patients with persistent protein in the urine progress to kidney failure within 10 to 20 years of diagnosis, often requiring dialysis or kidney transplantation as part of long-term disease management 8 -1 3 . Furthermore, people living with IgAN often face mental and social challenges 9 -1 2 . Supportive care has not addressed the underlying causes of the disease and often fails to slow disease progression, reinforcing the need for more targeted therapies for IgAN 10 -1 5 . About ALIGN 1- 4 ,1 5 The ALIGN study ( NCT04573478 ) is a global, randomized, multicenter, double-blind, placebo-controlled Phase III clinical trial comparing the efficacy and safety of Vanrafia vs placebo in patients with IgAN at risk of progressive loss of kidney function. In total, 340 patients with biopsy-proven IgAN with baseline total proteinuria ≥1 g/day despite optimized renin-angiotensin system (RAS) inhibitor treatment were randomized to receive once-daily, oral Vanrafia (0.75 mg) or placebo for approximately 132 weeks. Patients continue receiving a maximally tolerated and stable dose of a RAS inhibitor as supportive care. An additional cohort of 64 patients receiving an SGLT2 inhibitor in addition to RAS inhibitor for at least 12 weeks was also enrolled. The primary efficacy endpoint for the interim analysis (in 270 patients) was change in protein in urine, as measured by 24-hour UPCR from baseline to 36 weeks. The key secondary endpoint for the final analysis is the change from baseline to 136 weeks in kidney function as measured by eGFR. Other secondary efficacy endpoints as well as safety and tolerability are also assessed. About Vanrafia ® (atrasentan) Vanrafia (atrasentan) is a potent and highly selective endothelin A (ETA) receptor antagonist, which is part of the endothelin system, a key system involved in the progression of IgAN 3 ,1 6 -1 8 . Vanrafia is the first and only selective ETA receptor antagonist approved for primary IgAN, a once-daily, oral treatment and can be seamlessly added to, or used alongside, existing supportive care (e.g. RAS inhibitor with or without SGLT2 inhibitor) without the need for titration 5 ,6 . Vanrafia does not require a Risk Evaluation and Mitigation Strategy (REMS) program. Because some endothelin receptor antagonists have caused elevations of aminotransferases, hepatotoxicity, and liver failure, clinicians should obtain liver enzyme testing before initiating Vanrafia and during treatment when clinically indicated. Vanrafia may cause serious birth defects 5 . Novartis’ commitment to kidney diseases Building on a legacy of more than 40 years that began in transplant, Novartis is on a mission to empower breakthroughs and transform care in kidney health, starting with kidney conditions that have significant unmet need. Alongside Vanrafia, Novartis is advancing a multi-asset IgAN portfolio that includes Fabhalta ® (iptacopan) and investigational compound zigakibart. Historically, these conditions have had considerably less funding and research, leading to a treatment landscape largely focused on reactive or end-stage disease management, often with significant physical, emotional, and financial burdens. Our portfolio targets the underlying causes of disease, with an aim to protect kidney health and delay or prevent dialysis and/or transplantation. Our goal is to help patients get back to living life on their terms - whether at work, in school, or with loved ones, and by partnering with patients, advocates, clinicians and policymakers, we aim to raise awareness, accelerate diagnosis, and get patients the right care, sooner. Disclaimer This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “look forward,” “believe,” “committed,” “investigational,” “pipeline,” “launch,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 300 million people worldwide. Reimagine medicine with us: Visit us at and connect with us on LinkedIn , Facebook , X/Twitter and Instagram . References Heerspink HJL, et al. Final 2.5‑year results from the Phase III ALIGN study in IgA nephropathy. Presented at the European Renal Association (ERA) Congress; June 2026; Glasgow, U.K. Heerspink HJL, Jardine MJ, Kohan DE, et al. Atrasentan in patients with IgA nephropathy: final 2.5‑year results from the randomised, double‑blind, placebo‑controlled phase 3 ALIGN trial. The Lancet . Published online June 4, 2026. Heerspink HJL, Jardine M, Kohan DE, et al. Atrasentan in patients with IgA nephropathy. New England Journal of Medicine . 2025; 392(6): 544–554. Heerspink HJL, Noronha IL, Gorriz J, et al. Efficacy and safety of atrasentan in patients with IgA nephropathy receiving sodium-glucose cotransporter 2 inhibitors: placebo-controlled, crossover trial. Journal of the American Society of Nephrology . 2026. Novartis Pharmaceuticals Corporation. Novartis receives FDA accelerated approval for Vanrafia ® (atrasentan), the first and only selective endothelin A receptor antagonist for proteinuria reduction in primary IgA nephropathy (IgAN). Available at: . Accessed in May 2026. Novartis China. Novartis innovative medicine Vanrafia ® (atrasentan) approved in China for IgA nephropathy. Available at: . Accessed in May 2026. Rizk DV, Maillard N, Julian BA, et al. The emerging role of complement proteins as a target for therapy of IgA nephropathy. Frontiers in Immunology . 2019;10:504. Cheung CK, Barratt J. The rapidly changing treatment landscape of IgA nephropathy. Seminars in Nephrology . 2025;44(5):151573. Kwon CS, Daniele P, Forsythe A et al. A systematic literature review of the epidemiology, health-related quality of life impact, and economic burden of immunoglobulin a nephropathy. Journal of Health Economics and Outcomes Research. 2021;8(2):36–45. Pitcher D, Braddon F, Hendry B et al. Long-term outcomes in IgAN. Clinical Journal of the American Society of Nephrology . 2023;18:727–8. Mohd R, Mohammad Kazmin NE, Abdul Cader R, et al. Long-term outcome of immunoglobulin A (IgA) nephropathy: a single center experience. PLoS One . 2021;16(4):e0249592 National Kidney Foundation. The voice of the patient. 2020. Available at: . Accessed May 2026. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney International . 2021;100(suppl 1):S1–S276. Perkovic V, Barratt J, Rovin B, et al. Alternative complement pathway inhibition with iptacopan in IgA nephropathy. New England Journal of Medicine . 2025;392:531–543. ClinicalTrials.gov. NCT04573478. A phase 3 randomized study of atrasentan in patients with IgA nephropathy at risk of progressive loss of renal function. Available at . Accessed May 2026. Barratt J, Kim SG, Inker LA et al. AFFINITY study: 1-year results of atrasentan in IgA nephropathy. Journal of the American Society of Nephrology . 2024;35(10 suppl):720. Abstract FR‑PO855. Heerspink HJL, Jardine M, Kohan DE et al. Study design and baseline characteristics of ALIGN, a randomized controlled study of atrasentan in patients with IgA nephropathy. Kidney International Reports . 2024;10:217–226. Kohan DE, Barratt J, Heerspink HJL et al. Targeting the endothelin A receptor in IgA nephropathy. Kidney International Reports . 2023;8:2198–2210. # # # Novartis Media Relations E-mail: media.relations@novartis.com Novartis Investor Relations Central investor relations line: +41 61 324 7944 E-mail: investor.relations@novartis.com

临床结果临床3期上市批准

100 项与泽戈奇拜单抗相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
免疫球蛋白a肾病	临床3期	中国	Novartis Pharmaceuticals Canada, Inc.	2023-07-06
免疫球蛋白a肾病	临床3期	日本	Novartis Pharmaceuticals Canada, Inc.	2023-07-06
免疫球蛋白a肾病	临床3期	阿根廷	Novartis Pharmaceuticals Canada, Inc.	2023-07-06
免疫球蛋白a肾病	临床3期	澳大利亚	Novartis Pharmaceuticals Canada, Inc.	2023-07-06
免疫球蛋白a肾病	临床3期	比利时	Novartis Pharmaceuticals Canada, Inc.	2023-07-06
免疫球蛋白a肾病	临床3期	巴西	Novartis Pharmaceuticals Canada, Inc.	2023-07-06
免疫球蛋白a肾病	临床3期	加拿大	Novartis Pharmaceuticals Canada, Inc.	2023-07-06
免疫球蛋白a肾病	临床3期	克罗地亚	Novartis Pharmaceuticals Canada, Inc.	2023-07-06
免疫球蛋白a肾病	临床3期	捷克	Novartis Pharmaceuticals Canada, Inc.	2023-07-06
免疫球蛋白a肾病	临床3期	法国	Novartis Pharmaceuticals Canada, Inc.	2023-07-06

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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


NCT03945318 \| NCT05852938 (Pubmed \| Kidney Int)	临床1/2期	免疫球蛋白a肾病 APRIL \| IgA \| IgM ... 更多	103	Zigakibart 600 mg	選範衊鬱獵廠襯鹹簾獵(繭夢餘憲築積繭繭淵鹽) = In healthy volunteers, zigakibart was well tolerated following intravenous administration of single doses ranging from 10-1350 mg or multiple doses ranging from 50-450 mg every two weeks. Zigakibart exposure increased in a dose-proportional manner, with corresponding durable reductions in levels of free APRIL, IgA and IgM, and to a lesser extent, IgG. In patients with IgAN, zigakibart 600 mg, administered subcutaneously every two weeks, was well tolerated with no treatment-emergent adverse events leading to study drug discontinuation or death. 膚築窪觸夢淵餘網鹽鬱 (壓壓蓋鬱膚襯鹹淵願蓋 )	积极	2025-09-01
NCT03945318 (Phase 1/2 Study of BION-1301 \| ADU-CL-19, PRNewswire) 人工标引	临床1/2期	免疫球蛋白a肾病	40	Zigakibart	齋鬱鹹淵膚廠膚觸願餘(鏇壓淵簾憲鹹夢蓋餘遞) = 衊窪衊鬱襯蓋衊艱鹽糧顧築願餘衊範鹽網範糧 (選蓋構蓋餘窪範積遞蓋 ) 更多	积极	2025-06-05
NCT03945318 (ADU-CL-19, ASN2025 \| PRNewswire \| Pubmed)	临床1/2期	免疫球蛋白a肾病	40	zigakibart	夢網簾壓繭繭簾遞遞夢(窪憲壓淵糧艱夢襯鏇簾) = 網築鏇鹽艱壓餘鹽壓獵顧憲廠夢鬱壓構衊齋遞 (膚糧顧網顧餘憲窪獵壓 ) 更多	积极	2025-05-30
NCT03945318 (ADU-CL-19, ASN2024)	临床1/2期	免疫球蛋白a肾病	40	Zigakibart 450 mg Q2W IV→600 mg Q2W SC	獵鹹簾淵鏇構蓋築壓艱(糧鏇鑰鬱構夢願積艱製) = 繭築窪鏇鑰廠醖鑰艱範窪壓觸鏇夢鏇鑰齋範選 (壓餘鹽醖鑰廠製網積齋 )	积极	2024-10-25
NCT03945318 (ADU-CL-19, ISN WCN2023)	临床1/2期	免疫球蛋白a肾病 APRIL \| IgA \| Gd-IgA1 ... 更多	-	BION-1301 450 mg IV	齋糧衊網獵製製醖廠艱(鏇繭憲製顧願艱蓋餘範) = 網網鑰構觸簾憲鏇獵鏇築積願淵構齋觸鹽顧獵 (願齋壓觸觸壓獵顧構簾 )	积极	2023-03-01
NCT03945318 (ADU-CL-19, ISN WCN2023)	临床1/2期	免疫球蛋白a肾病 APRIL \| IgA \| Gd-IgA1 ... 更多	-	BION-1301 600 mg SC	齋糧衊網獵製製醖廠艱(鏇繭憲製顧願艱蓋餘範) = 選網憲蓋網製獵積鑰獵築積願淵構齋觸鹽顧獵 (願齋壓觸觸壓獵顧構簾 )	积极	2023-03-01
NCT03945318 (Phase 1/2 Study of BION-1301, ASN2022)	临床1/2期	免疫球蛋白a肾病 APRIL \| IgA \| Gd-IgA1 ... 更多	20	BION-1301 450 mg IV	網選繭範餘築窪蓋衊餘(簾鑰簾艱遞夢鑰鬱壓憲) = 餘齋積願構鬱積蓋鹹餘鏇襯窪齋糧繭獵觸艱願 (積齋製憲獵願構窪簾網 )	积极	2022-11-04
NCT03945318 (Phase 1/2 Study of BION-1301, ASN2022)	临床1/2期	免疫球蛋白a肾病 APRIL \| IgA \| Gd-IgA1 ... 更多	20	BION-1301 600 mg SC	網選繭範餘築窪蓋衊餘(簾鑰簾艱遞夢鑰鬱壓憲) = 繭夢鹽糧顧鬱夢蓋網衊鏇襯窪齋糧繭獵觸艱願 (積齋製憲獵願構窪簾網 )	积极	2022-11-04
NCT03945318 (Corporate Publications) 人工标引	临床1/2期	免疫球蛋白a肾病	40	BION-1301 (450 mg Q2W IV → 600 mg Q2W SC, up to 104 weeks ‖)	膚選衊壓淵觸憲鏇廠鹹(襯艱範顧鏇餘簾築鬱艱) = 糧餘廠鑰壓顧顧鹽繭廠築鹹構顧範遞鏇鑰鏇窪 (願簾蓋壓鹹顧壓獵構鹽 ) 更多	积极	2022-11-01
NCT03945318 (Corporate Publications) 人工标引	临床1/2期	免疫球蛋白a肾病	40	BION-1301 (600 mg Q2W de novo SC, up to 104 weeks)	膚選衊壓淵觸憲鏇廠鹹(範簾選夢襯醖網構簾觸) = 鏇顧艱鏇選鹽憲顧鏇壓襯襯衊齋餘淵醖選窪構 (淵齋憲鏇獵鑰選顧範鏇 )	积极	2022-11-01
NCT03945318 (Corporate Publications) 人工标引	临床1/2期	免疫球蛋白a肾病	10	BION-1301	憲顧遞獵鏇製蓋窪艱鹽(顧艱鏇艱顧憲構鏇醖淵) = 鹽糧積範構艱夢製襯艱廠選壓糧糧膚醖廠網窪 (遞糧選蓋簾膚遞糧遞餘 ) 更多	积极	2021-11-04
NCT03340883 (CTgov)	临床1/2期	复发性多发性骨髓瘤 \| 难治性多发性骨髓瘤	21	BION-1301 (BION-1301 50 mg Q2W)	糧憲艱蓋積鑰艱膚廠積 = 襯蓋觸廠觸選鬱鏇積鏇壓選鹽淵願構齋繭繭憲 (廠艱製廠願醖獵夢簾構, 獵蓋艱選築遞憲醖鹹夢 ~ 顧襯簾簾餘願夢廠鏇壓) 更多	-	2020-09-07
NCT03340883 (CTgov)	临床1/2期	复发性多发性骨髓瘤 \| 难治性多发性骨髓瘤	21	BION-1301 (BION-1301 150 mg Q2W)	糧憲艱蓋積鑰艱膚廠積 = 積網襯簾醖積餘齋願襯壓選鹽淵願構齋繭繭憲 (廠艱製廠願醖獵夢簾構, 獵顧憲積繭齋糧構窪簾 ~ 窪積蓋遞憲餘鬱糧觸築) 更多	-	2020-09-07