Atrasentan Hydrochloride

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

IgA肾病是我国最常见的原发性肾小球疾病，但这个病的脾气很不一样——有的人一辈子没什么大事，有的人十来年就到了尿毒症。 差别在哪？除了病本身，治疗用没用药、用没用到点上，非常关键。 目前公认的发病机制叫“四重打击”：先产生不正常的IgA，身体把它当敌人，产生抗体，抗体和敌人抱团形成复合物，最后这些复合物沉积在肾小球里，把肾脏搞坏了。 针对这几个环节，药物也分成四大类：基础支持药、免疫调节药、靶向新药，以及中医中药和辅助治疗。 基础支持治疗(12种) 1. 贝那普利(普利类) 这药主要干两件事：降血压、降肾小球里面的压力。肾小球压力降下来，蛋白漏得就少。不管你有没有高血压，只要尿蛋白高，我都建议用。 起始一天5毫克，慢慢往上加，最大可以到一天40毫克，分一两次吃。肾不好的人要从更小剂量开始。注意：吃了之后肌酐涨一点(30%以内)是好事，说明药起效了，别自己停药。普利和沙坦不能一起吃。 2. 厄贝沙坦(沙坦类) 沙坦和普利作用差不多，但沙坦一般不引起干咳。如果你吃普利咳得厉害，换这个。 起始75到150毫克，一天一次。目标是找到你能承受的最大剂量，不是光看血压正常不正常。常用量75到300毫克每天。要定期查血钾和肾功能。 3. 缬沙坦(沙坦类) 跟厄贝沙坦是同类，效果也类似。起始40到80毫克，一天一次，可以加到320毫克。 4. 氯沙坦(沙坦类) 沙坦里资格最老的一个。它有个小优点——轻微降尿酸，适合合并尿酸高的患者。起始25到50毫克，维持量50到100毫克。 5. 雷米普利(普利类) 长效，一天吃一次就行，方便。起始1.25到2.5毫克，可加到10毫克。 6. 培哚普利(普利类) 组织穿透力强，对心肾保护作用不错。起始2毫克每天，维持4到8毫克。肾功能差的人要减量。 7. 赖诺普利(普利类) 不经过肝脏代谢，肝功能不好的人也能用。起始2.5到5毫克每天。主要从肾排，肾不好要减量。 8. 达格列净(列净类) 本来是个降糖药，后来发现不降糖的人吃也能保护肾脏。它能降低肾小球的工作负荷，相当于让肾脏“省着点用”。一般用在普利/沙坦效果还不够的患者身上。一天10毫克，生病时(拉肚子、感染、脱水)要暂停。注意多喝水，防止尿路感染。 9. 恩格列净(列净类) 跟达格列净差不多，心血管保护证据更强一些。一天10毫克，可加到25毫克。 10. 非奈利酮 比较新的药，抗炎抗纤维化。目前主要用在糖尿病肾病，但IgA肾病也在研究。起始10或20毫克每天，要看肾功能和血钾水平。用的时候必须盯着血钾。 11. 鱼油(ω-3脂肪酸) 它不是药，是保健品。研究说长期吃鱼油能让IgA肾病进展慢一点，但效果不算大。一天2到4克，空腹吃。不能代替普利/沙坦。 12. 碳酸氢钠(小苏打) 肾功能差的人容易酸中毒，酸中毒会加速肾纤维化。吃小苏打把酸纠过来，肾功能能掉得慢些。根据血碳酸氢根水平调整，一般一天1到3克。别吃多，吃多碱中毒。 靶向治疗(11种) 13. 布地奈德肠溶胶囊(耐赋康) 全球第一个针对IgA肾病病因的药。它靶向肠道里的免疫细胞，减少异常IgA的产生。一天16毫克，早上空腹吃，整粒吞。疗程9个月，最后两周减到8毫克。副作用有痤疮、血压高。别吃葡萄柚。这是目前最有代表性的靶向药。 14. 斯帕森坦(司帕生坦) 一个药管两条路：同时阻断内皮素和血管紧张素受体。适用于尿蛋白比较多的患者。起始200毫克一天，两周后加到400毫克。可能引起水肿和贫血。 15. 伊普可泮 补体B因子抑制剂。补体是造成肾脏损伤的直接凶手，把它按住，肾就能少受罪。一天两次，一次200毫克口服。 16. 阿曲生坦 阻断内皮素A受体，减少蛋白尿。一天0.75毫克。已在美国获批。 17. Sibeprenlimab APRIL抑制剂，单抗类。皮下注射，每4周一次。2025年底刚在美国获批。 18. Povetacicept BAFF/APRIL双重阻断剂，已获突破性疗法认定，还在临床试验阶段。 19. Zigakibart 也是靶向APRIL的单抗，在III期试验中。 20. 泰它西普 国产的双靶点生物制剂(BLyS/APRIL)，用于难治性IgA肾病，尤其激素耐药或反复复发的。皮下注射，剂量需遵医嘱。 21. HSK39297 国产补体B因子抑制剂，一天一次。2026年公布的数据显示，12周能降蛋白尿约50%。 22. 羟氯喹 本来是抗疟疾的，对IgA肾病有轻度的免疫调节作用。适合轻症患者，尤其只有血尿、蛋白尿不多的。联合半量激素效果不错，副作用比足量激素小。一天200毫克，分1到2次吃。长期用要查眼底，防视网膜损伤。 23. Ziltivekimab 抗IL-6单抗，还在研究中，通过抑制炎症通路起作用。 免疫抑制剂(8种) 24. 泼尼松(强的松) 最经典的激素。抗炎、抑制免疫。现在指南优先推荐布地奈德，搞不到布地奈德才用全身激素。起始每天0.6到0.8毫克每公斤体重，最多60毫克。足量用2到3个月，然后慢慢减，总疗程6到9个月。不能突然停药。长期用要注意血糖、血压、骨头、感染。 25. 甲泼尼龙 比泼尼松更强。常规口服用法类似，重症时可以用静脉冲击(住院用)。 26. 环磷酰胺 很猛，毒性也大。只在最重的情况下用，比如病理报告写着大量新月体(超过40%)。静脉冲击或口服，必须大量喝水防止出血性膀胱炎。要勤查血常规。 27. 霉酚酸酯(骁悉) 抑制淋巴细胞，副作用比环磷酰胺小一些。用于激素耐药或重症患者。一天1到1.5克，分两次。可和激素联用。需监测血常规和肝功能。 28. 硫唑嘌呤 用于激素依赖或抵抗患者的维持治疗，但证据不够硬。一天1到2毫克每公斤体重。用药前最好查TPMT基因，防止严重骨髓抑制。 29. 环孢素 抑制T细胞，用于难治性病例，不是一线。一天3到5毫克每公斤体重，分两次。要监测血药浓度。最大的顾虑是肾毒性。 30. 他克莫司(FK506) 跟环孢素同类，效果更强。起始0.05到0.1毫克每公斤体重，分两次空腹吃。监测血药浓度。副作用有肾毒性、手抖、血糖高。 31. 来氟米特 超说明书用于IgA肾病。联合泼尼松有一定效果。负荷剂量一天50毫克用3天，然后维持一天20毫克。停药后体内还有残留，换药要小心。副作用有脱发、血压高、转氨酶高。 中医中药与辅助治疗(4种) 32. 黄葵胶囊 黄蜀葵花提取物，清热利湿、活血。能降蛋白、辅助改善血尿。适合轻中度蛋白尿的患者。一天3次，一次2.5克，随餐吃。少数人胃不舒服。 33. 金水宝胶囊 人工虫草菌粉，补肺肾、减轻代谢负担。现代研究认为有抗炎、抗氧化、减轻肾间质损伤的作用。一天3次，一次3粒。一般要连吃3到6个月才见效。 34. 百令胶囊 也是发酵虫草菌丝体，免疫调节辅助。可和羟氯喹联用。一天3次，一次3粒。急性感染期暂停。 35. 中药辨证方剂 IgA肾病在中医里分好几种类型：气阴两虚、阴虚血热、肾精不固、阴虚浊毒等。不同证型用不同方子，比如参芪地黄汤、升降散、金锁固精丸等。一定要找正规中医师辨证开方，一人一方。千万别自己抓“秘方”，有些中药含马兜铃酸，会伤肾。 如果有肾病方面问题，可添加微信，一对一免费指导