Zigakibart

Fabhalta lowered likelihood of progression to kidney failure by 43% in APPLAUSE-IgAN study1 40.7% of patients on Fabhalta demonstrated sustained reduction of protein in urine over two years1 Fabhalta granted priority review by FDA for traditional approval Basel, March 29, 2026 – Novartis today announced final two-year results from the Phase III APPLAUSE‑IgAN study of Fabhalta® (iptacopan) in IgA nephropathy (IgAN). Fabhalta demonstrated a statistically significant, clinically meaningful improvement in estimated glomerular filtration rate (eGFR) slope, a key marker of kidney function, compared with placebo1. Fabhalta consistently outperformed placebo across key kidney outcomes over two years, demonstrating a slowing of disease progression and the potential to preserve kidney function in IgAN1.The results were published in the New England Journal of Medicine and simultaneously presented as late‑breaking data at the 2026 World Congress of Nephrology (WCN). “Persistent kidney inflammation is a hallmark of IgAN, and a key driver of disease progression, leading to ongoing kidney damage and loss of function over time,” said Vlado Perkovic, MD, Professor of Medicine and Provost, University of New South Wales, and Steering Committee Co‑Chair of the APPLAUSE‑IgAN study. “These results are important because they show that Fabhalta can reduce the risk of disease progression, help preserve kidney health, and address outcomes associated with long-term disease burden.” Key efficacy results over two years1 Endpoint Fabhalta Placebo Effect vs. placebo Kidney function (eGFR slope) –3.10 mL/min/1.73 m²/yr –6.12 mL/min/1.73 m²/yr 3.02 mL/min/1.73 m2/yr (49.3% slower decline) Composite kidney failure events*† 21.4% 33.5% HR 0.57 (43% lower likelihood) Proteinuria† (24-hour UPCR <1g/g) 40.7% achieved target 23.7% achieved target — *Composite kidney failure endpoint: reaching either sustained ≥30% decline in eGFR relative to baseline, sustained eGFR <15 mL/min/1.73 m², initiation of maintenance dialysis, kidney transplant, or death from kidney failure†As measured by percentage of patients“The two-year results demonstrate that Fabhalta consistently and meaningfully slows kidney function decline in high-risk patients with IgAN,” said Ruchira Glaser, MD, MS, Global Head, Cardiovascular, Renal and Metabolic Development, Novartis. “This progress reflects years of focused research and supports our efforts to advance more targeted treatment options to help preserve kidney health in people living with IgAN.”The safety profile of Fabhalta over two years was consistent with previous findings. Rates of adverse events and treatment discontinuation were low and similar between Fabhalta and placebo1,2.Fabhalta received accelerated approval in the U.S. and China for proteinuria reduction in adults with IgAN based on data from a prespecified interim analysis of the APPLAUSE-IgAN study2,3. The two-year data were submitted to the U.S. Food and Drug Administration for traditional approval. Fabhalta was granted priority review based on the novel mode of action and the strength of the data. Alongside Fabhalta, Novartis continues to advance its multi-asset IgAN portfolio, which also includes Vanrafia® (atrasentan) and investigational compound zigakibart.About IgANIgAN is a progressive autoimmune kidney disease, with approximately 25 people per million worldwide newly diagnosed each year4,5. 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 eGFR6. Up to 50% of patients with persistent proteinuria progress to kidney failure within 10 to 20 years of diagnosis, often requiring dialysis or kidney transplantation as part of long-term disease management5-10.Furthermore, people living with IgAN often face mental and social challenges6-9. 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 IgAN7-12. About APPLAUSE-IgANAPPLAUSE-IgAN (NCT04578834) is a global, randomized, double-blind, placebo-controlled Phase III study evaluating Fabhalta in adults with biopsy-confirmed IgAN and persistent proteinuria despite optimized supportive care. Patients were randomized 1:1 to receive Fabhalta or placebo and were followed for up to 24 months11. The primary endpoint was the annualized total eGFR slope over 24 months. Key secondary endpoints included time to first composite kidney failure event and changes in proteinuria over 9 months1.The most common adverse events with Fabhalta were mainly mild-to-moderate infections (such as COVID-19 and upper respiratory tract infection), headache, diarrhea, and hyperlipidemia, with overall adverse event rates comparable to placebo1.About Fabhalta® (iptacopan)Fabhalta (iptacopan) is an oral Factor B inhibitor designed to selectively target the alternative complement pathway, one of several key drivers of inflammation and kidney damage in IgAN4,12,13. By inhibiting Factor B, Fabhalta aims to reduce ongoing complement-mediated injury and slow disease progression. Fabhalta has received regulatory approvals in multiple complement-mediated diseases, including IgAN, and is being evaluated across a range of rare kidney conditions.Novartis’ commitment to kidney diseasesBuilding 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.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.DisclaimerThis 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 file with 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 https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram.References Novartis. Data on file Novartis Pharmaceuticals Corporation. Novartis receives FDA accelerated approval for Fabhalta® (iptacopan), the first and only complement inhibitor for the reduction of proteinuria in primary IgA nephropathy (IgAN) (2024). Available at: https://www.novartis.com/news/media-releases/novartis-receives-fda-accelerated-approval-fabhalta-iptacopan-first-and-only-complement-inhibitor-reduction-proteinuria-primary-iga-nephropathy-igan. Accessed March 2026 Novartis China. Novartis’ innovative medicine Fabhalta® (iptacopan) approved in China for a new indication. Novartis China website (in Mandarin). Available at: https://www.novartis.com.cn/news/nuohuazaiyingshenzangjibingzhiliaolingyulichengbeichuangxinyaowufeihedayansuanyipukepanjiaonangigashenbingshiyingzhengzaizhongguohuopi. Accessed March 2026 Rizk DV, Maillard N, Julian BA, et al. The emerging role of complement proteins as a target for therapy of IgA nephropathy. Front Immunol 2019;10:504. Cheung C, Barratt J. The rapidly changing treatment landscape of IgA nephropathy. Semin Nephrol. 2025;44:151573. 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. J Health Econ Outcomes Res. 2021;8:36–45. Pitcher D, Braddon F, Hendry B et al. Long-term outcomes in IgAN. Clin J Am Soc Nephrol. 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. National Kidney Foundation. The voice of the patient (2020). Available at: https://igan.org/wp-content/uploads/2021/01/VOP_IgAN_12-7-20__FNL.pdf. Accessed March 2026. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases. Kidney Int. 2021;100:S1–276. Clinicaltrials.gov. NCT04578834. Study of Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients (APPLAUSE-IgAN). Available at: https://clinicaltrials.gov/study/NCT04578834. Accessed March 2026. Perkovic V, Barratt J, Rovin B, et al. Alternative complement pathway inhibition with iptacopan in IgA nephropathy. N Engl J Med. 2025;392:531–543. Chiu YL, Lin WC, Shu KH, et al. Alternative complement pathway is activated and associated with galactose-deficient IgA(1) antibody in IgA nephropathy patients. Front Immunol 2021;12:638309. # # # 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

☝ 点击上方 一键预约 ☝   最新最热的医药健康新闻政策 摩熵咨询最新发布的《IgA 肾病药物研发全景及已上市药物市场竞争格局报告》，紧扣行业脉搏，以临床需求为锚点、产业视角为纲，系统梳理了IgA肾病从病理机制到市场竞争的全链条逻辑。上篇文章已系统阐述了IgA肾病的病理特征、流行病学及诊疗现状，基于摩熵医药数据库的深度洞察，本文将聚焦药物研发的前沿动态，从研发阶段分布、靶点机制突破到管线布局特点，全方位铺展IgA肾病药物研发的全景图谱，为制药企业研发决策、投资机构赛道布局及临床工作者治疗选择提供了关键决策参考。 01 IgA肾病药物 研发情况概览 全球研发活动集中于临床中后期，跨国药企重视中国市场布局。 摩熵医药数据库显示，截至2025年12月，全球研发活动集中于临床中后期，II期临床产品数量达到19个，III期临床的管线达10个。预计近年该适应症领域将有大量产品上市，且已上市药物也是在近期上市，市场预计将快速从“无药可用”成长至激烈竞争。 数据来源：摩熵医药数据库（统计时间截至2025.12） 中国研发管线与全球趋势基本同步，同时也能发现海外药企对中国市场的重视。如阿曲生坦（中国上市许可持有人：诺华）、伊普可泮（中国上市许可持有人：诺华）在全球首次上市后，都在1年内完成中国上市。此外，处于申请上市阶段的斯贝利单抗，已提前启动上市前医学推广布局。 数据来源：摩熵医药数据库 02 靶点概览 IgA 肾病的发病机制以“四步打击学说”为核心，药物研发靶点的布局也围绕这一核心机制展开。目前，已有多个靶点形成具备一定成熟度的研发管线，核心研发方向集中于阻断 “第一次打击”（异常糖基化 IgA1 生成）与抑制 “第四次打击”（免疫复合物沉积引发的肾脏损伤）两大关键环节，通过精准干预疾病进展的核心通路，实现对肾功能的保护与疾病进展的延缓。 截图来源：《IgA肾病药物研发全景及已上市药物市场竞争格局报告》 第1次打击：抑制异常糖基化 IgA1（Gd-IgA1）的产生 关键靶点：黏膜相关淋巴组织（MALT）功能失调、APRIL、TACI/BCMA、糖皮质激素受体（GCCR）等。 代表药物：靶向释放布地奈德（Budesonide）：阻断异常 Gd-IgA1 产生（Nefecon/耐赋康）。 APRIL 抑制剂：阻断 B 细胞活化（Sibeprenlimab/司帕生坦）。 TACI/BCMA 靶向：调节 B 细胞分化（泰它西普） 第4次打击：抑制免疫复合物沉积与肾脏损伤 关键靶点：补体系统（C3/C5/CFB/MASP-2）、内皮素受体（ET-A）、血管紧张素受体（AT1R）。 代表药物：补体抑制剂：伊普可泮（已上市）等，抑制 C3/C5 介导的炎症。 双重内皮素/血管紧张素受体拮抗剂：Sparsentan、阿曲生坦，改善蛋白尿。 ENT 抑制剂：延缓肾功能进展（Dilazep Hydrochloride） 03 已上市药物靶点解读 1.靶向释放布地奈德（Budesonide）：阻断异常糖基化IgA1（Gd-IgA1）产生 黏膜相关淋巴组织（尤其是肠道相关淋巴组织GALT）是人体IgA合成的主要场所，其中回肠末端的派尔集合淋巴结（Peyer’spatches）作为抗原采样和免疫诱导的关键部位，更是黏膜型IgA1生成的核心来源。 截图来源：《IgA肾病药物研发全景及已上市药物市场竞争格局报告》 在IgA肾病病理状态下，GALT功能失调导致血清中半乳糖缺陷型IgA1（Gd-IgA1）水平异常升高，这类致病性IgA1会形成免疫复合物并沉积于肾小球系膜区，最终引发肾脏损伤；此外，肠道菌群失衡、遗传因素（如C1GALT1基因多态性）等也会通过调控黏膜IgA合成与糖基化过程，参与疾病的发生与进展。 靶向释放布地奈德（商品名：耐赋康）是全球首个IgA肾病对因治疗药物，采用独特的肠溶胶囊技术，将活性成分布地奈德靶向递送至回肠末端的派尔集合淋巴结，抑制异常IgA1的产生，从源头阻断“第一次打击”的发生。 2.APRIL抑制剂：阻断异常糖基化IgA1（Gd-IgA1）产生 细胞因子APRIL是肿瘤坏死因子α超家族成员，通过其在4-hit过程中的作用，是IgA肾病发病机制的重要起始和维持因子。通过结合跨膜激活剂和调节钙化的环红蛋白配体互助体，APRIL促进活化B细胞向产生Gd-IgA1的质细胞的类别转换。 截图来源：《IgA肾病药物研发全景及已上市药物市场竞争格局报告》 目前，APRIL抑制剂已成为IgA肾病研发管线中最成熟的靶点之一，全球已有多个药物进入临床后期或获批上市。摩熵医药数据库显示，其中斯贝利单抗（CAS：2382896-07-1）作为该类别的代表药物已在多个国家和地区获批上市，其临床数据显示可显著降低患者血清Gd-IgA1水平和尿蛋白排泄量。此外，处于III期临床阶段的zigakibart（CAS：2642175-46-8）和阿塞西普（CAS：845264-92-8）也展现出良好的疗效前景，有望进一步丰富APRIL靶向治疗的选择。 3.补体抑制剂/MASP-2抑制剂：抑制肾脏沉积与损伤 补体系统作为先天免疫系统的重要组成部分，在IgA肾病的"第3次打击"和"第4次打击"中扮演关键角色。该系统由50多种血浆蛋白和细胞表面受体组成，可通过经典通路（CP）、凝集素通路（LP）和旁路通路（AP）三条相互关联的途径激活，最终均交汇于核心蛋白C3的裂解，产生具有调理作用的C3b和促炎作用的C3a。后续进一步形成C5转化酶并组装膜攻击复合物（MAC），实现对病原体的直接裂解、促进免疫细胞吞噬及放大炎症反应的功能，同时机体存在精密的调控机制避免补体过度活化损伤自身组织。 截图来源：《IgA肾病药物研发全景及已上市药物市场竞争格局报告》 在IgA肾病患者中，沉积于肾小球系膜区的Gd-IgA1免疫复合物可通过凝集素通路（主要依赖MASP-2）和旁路通路激活补体系统，引发局部炎症反应和肾小球损伤。补体抑制剂通过选择性阻断特定补体成分，可有效抑制补体过度活化导致的肾脏损伤，同时保留补体系统的抗感染功能。 伊普可泮是首个获批的补体通路抑制剂。此外，该靶点领域还有多个在研药物处于临床后期阶段，包括HRS-5965（Ⅲ期临床）、sefaxersen sodium（Ⅲ期临床）、瑞利珠单抗（Ⅲ期临床）、lanoracopan（II期临床）、Vemircopan（II期临床）等。（该靶点药物较多，详情请参考本章节附录部分） 4.内皮素受体拮抗剂：抑制肾脏沉积与损伤 内皮素（ET）系统在肾脏生理功能调节和病理损伤过程中发挥核心作用，成为IgA肾病"第4次打击"环节的重要干预靶点。内皮素是一类含21个氨基酸的多肽类血管收缩物质，家族包括ET-1、ET-2、ET-3三种异构体，其中ET-1是肾脏中唯一表达的血管收缩型异构体，通过与ETA和ETB两种受体结合发挥生物学效应。 ETA和ETB受体广泛分布于肾小球足细胞、系膜细胞及肾入球/出球小动脉血管壁。在生理状态下，内皮素系统参与调节肾小球血流动力学和水钠平衡；而在病理状态下，ET-1优先结合ETA受体，既加剧肾小动脉收缩、升高肾小球内压，又损伤足细胞、诱导系膜细胞增殖，还会促进TGF-β等促纤维化因子释放。 该靶点IgAN药物：阿曲生坦（已上市）、sparsentan（已上市）、diosuxentan（Ⅲ期临床）、HS-10390（II期临床）、SAL-0120（I期临床） 5.双重内皮素/血管紧张素受体拮抗剂：抑制肾脏沉积与损伤 内皮素A（ETA）受体是内皮素受体家族的亚型之一，属于G蛋白偶联受体。它的配体是内皮素-1（ET-1），二者结合后会触发血管收缩、细胞增殖与纤维化等生理病理效应。 血管紧张素II亚型1（AT1）受体是肾素-血管紧张素-醛固酮系统（RAAS）的关键效应受体，广泛表达于肾脏的肾小球、肾小管、血管内皮等部位。其配体为血管紧张素II（AngII），结合后会引发肾小球出球小动脉收缩、醛固酮分泌增加等反应。 在IgA肾病中，肾脏局部AngⅡ水平升高，激活AT1受体后会导致入球小动脉收缩，升高肾小球内灌注压，破坏肾小球滤过屏障，促使蛋白尿增加；同时还会诱导促纤维化因子表达。并且肾脏内也会过度分泌ET-1。 该靶点IgAN药物：sparsentan（已上市）、HS-10390（II期临床） 6.ENT抑制剂：延缓肾功能进展 hENT1（编码基因SLC29A1）是人类平衡型核苷转运体（hENTs）家族的核心成员，属于SLC29基因家族编码的整合膜蛋白，是广泛分布于人体组织（包括肾脏、心脏、脑等）的双向易化扩散转运体。可介导细胞外腺苷快速进入细胞内，或促进细胞内腺苷向外释放，通过双向转运精准调节胞外腺苷浓度。 胞外腺苷是嘌呤能信号通路的关键信号分子，其水平变化会直接影响炎症反应、细胞增殖、血管张力等多种生理过程。IgA肾病患者的血液常处于高凝状态，血小板易被免疫复合物等激活，参与肾小球内的微血栓形成和炎症反应。 该靶点IgAN药物：DilazepHydrochlorideHydrate（已上市） 附录：针对“第1次打击”的靶点管线介绍 关键环节：肠道/黏膜处产生异常糖基化IgA1（Gd-IgA1）。 靶点：包括补体通路（如ADAR）、B细胞相关靶点（如BCMA、BLyS）、糖皮质激素受体（GCCR）等，对应IgA肾病的免疫/炎症核心环节。 数据来源：摩熵医药数据库 附录：针对“第4次打击”的靶点管线介绍 关键环节：免疫复合物沉积于肾小球系膜区后，激活补体系统。 靶点：以补体系统分子为主（如C3、C5、CFB、CFD等）。 数据来源：摩熵医药数据库 关键环节：补体激活、足细胞/系膜细胞损伤。 靶点：包含血管活性因子靶点（如AGT、ET-A）、免疫靶点（CD38）、补体通路靶点（CF、MASP2）、炎症通路靶点（IRAK4）等。 数据来源：摩熵医药数据库 近期更多摩熵咨询热门报告，识别下方二维码领取 （来源：摩熵医药） 药闻康策 新媒体矩阵微信公众号 点击下方  一键关注 【免责声明】 1.“药闻康策”部分文章信息来源于网络转载是出于传递更多信息之目的，并不意味着赞同其观点或证实其内容的真实性。如对内容有疑议，请及时与我司联系。2.“药闻康策”致力于提供合理、准确、完整的资讯信息，但不保证信息的合理性、准确性和完整性，且不对因信息的不合理、不准确或遗漏导致的任何损失或损害承担责任。3.“药闻康策”所有信息仅供参考，不做任何商业交易或医疗服务的根据，如自行使用“药闻康策”内容发生偏差，我司不承担任何责任，包括但不限于法律责任，赔偿责任。 欢迎转发分享、点赞、点在看