The research study is being done to see if ziltivekimab can be used to treat people who were admitted to hospital because of a heart attack. Ziltivekimab might reduce development of heart disease, thereby preventing new heart attacks or strokes. Participants will either get ziltivekimab (active medicine) or placebo (a dummy medicine which has no effect on the body). Which treatment participants get is decided by chance. The chance of getting ziltivekimab or placebo is the same. The participant will need to inject the study medicine into a flat skin surface in there stomach, thigh, or upper arm once every month. Ziltivekimab is not yet approved in any country or region in the world. It is a new medicine that doctors cannot prescribe. The study will last for about 2 years.

开始日期2024-06-25

申办/合作机构

Novo Nordisk A/S

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100 项与 Ziltivekimab 相关的临床结果

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100 项与 Ziltivekimab 相关的转化医学

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100 项与 Ziltivekimab 相关的专利（医药）

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项与 Ziltivekimab 相关的文献（医药）

2024-12-01·Current Atherosclerosis Reports

“Anti-inflammatory Therapies in Atherosclerosis – Where are we going?”

Review

作者: Budoff, Matthew ; Iskander, Beshoy ; Kambalapalli, Soumya ; Roy, Sion K ; Krishnan, Srikanth ; Lakshmanan, Suvasini ; Ichikawa, Keishi ; Punnanithinont, Natdanai

PURPOSE OF REVIEW:

Inflammation has been commonly known for the past decade as a part of the pathophysiology of atherosclerosis, along with lipid accumulation. However, some patients with optimized lipid-lowering therapy still have elevated inflammatory biomarkers. Anti-inflammation therapies were developed to eradicate this residual risk. We summarized the primary inflammatory pathway and recent clinical trials in anti-inflammation therapies.

RECENT FINDINGS:

Colchicine Cardiovascular Outcomes Trial (COLCOT) and LoDoCo2 (Colchicine Reduces Risk of Major Cardiovascular Events in Chronic Coronary Disease) found that low-dose colchicine significantly reduced cardiovascular death, myocardial infarction (MI), ischemic stroke and coronary revascularization in patients with recent MI within 30 days and chronic coronary disease respectively. The US Food and Drug Administration approved low-dose colchicine in 2023 for patients with established atherosclerotic cardiovascular disease (ASCVD). However, its use was limited for chronic kidney disease (CKD) patients. Reduction in Inflammation in Patients with Advanced Chronic Renal Disease Utilizing Antibody Mediated Interleukin-6 Inhibition (RESCUE) was conducted using Ziltivekimab, an IL-6 ligand monoclonal antibody and found that it significantly reduced high-sensitivity C-reactive protein, an inflammatory surrogate marker. There is an ongoing phase-3 clinical trial, Ziltivekimab Versus Placebo Cardiovascular Outcomes in Participants with Atherosclerotic Cardiovascular Disease, Chronic Kidney Disease, and Systemic Inflammation trial (ZEUS), which will be essential for further anti-inflammation therapy for patients with CKD. Numerous clinical trials have investigated anti-inflammation therapies. Colchicine is by far the only one that has the potential to be widely used due to its cost-effectiveness. Further research is needed on other novel anti-inflammation therapies and their real-world implementation.

2024-06-01·Current opinion in lipidology

C-reactive protein, pharmacological treatments and diet: how to target your inflammatory burden

Review

作者: Bay, Benjamin ; Arnold, Natalie ; Waldeyer, Christoph

Purpose of review:

This article focuses on pharmacological agents as well as dietary changes aimed at the reduction of the inflammatory burden measured by circulating C-reactive protein concentrations.

Recent findings:

Over the last years, repurposed as well as new anti-inflammatory agents have been investigated in outcome trials in the cardiovascular field. Currently, a specific inhibition of the inflammatory cascade via the interleukin-6 ligand antibody ziltivekimab is being explored in large-scale outcome trials, after the efficacy of this agent with regard to the reduction of inflammatory biomarkers was proven recently. Next to the investigated pharmacological agents, specific dietary patterns possess the ability to improve the inflammatory burden. This enables patients themselves to unlock a potential health benefit ahead of the initiation of a specific medication targeting the inflammatory pathway.

Summary:

Both pharmacological agents as well as diet provide the opportunity to improve the inflammatory profile and thereby lower C-reactive protein concentrations. Whilst advances in the field of specific anti-inflammatory treatments have been made over the last years, their broad implementation is currently limited. Therefore, optimization of diet (and other lifestyle factors) could provide a cost effective and side-effect free intervention to target low-grade vascular inflammation.

2024-04-01·JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

Impacts of pro‐inflammatory cytokines variant on cardiometabolic profile and premature coronary artery disease: A systematic review and meta‐analysis

Review

作者: Luo, Zhi ; Wei, Baozhu ; Lin, Yi ; Chen, Yuan ; Liu, Yang

Abstract:

Interleukin‐6 (IL‐6), a pivotal pro‐inflammatory cytokine, is closely linked to vascular wall thickening and atherosclerotic lesion. Since serum IL‐6 levels are largely determined by the genetic variant in IL‐6, this study was conducted to investigate whether the IL‐6 variant impacts cardiometabolic profile and the risk of premature coronary artery disease (PCAD). PubMed, Cochrane Library, Central, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ClinicalTrials.gov were searched from May 13, 2022 to June 28, 2023. In total, 40 studies (26,543 individuals) were included for the analysis. The rs1800795 (a function variant in the IL‐6 gene) C allele was linked to higher levels of low‐density lipoprotein cholesterol (LDL‐C), total cholesterol (TC), fasting plasma glucose (FPG), body mass index (BMI), and waist circumference (WC), and a lower levels of high‐density lipoprotein cholesterol (HDL‐C). However, no significant association was observed of rs1800795 with triglycerides (TG), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Interestingly, a significant association was detected between rs1800795 and PCAD. Subgroup analyses indicted that the impacts of rs1800795 on cardiometabolic risk factors were significant in Caucasians but stronger in obese patients. In contrast, the impact of rs1800795 on PCAD was significant in brown race population. In summary, rs1800795 had a slight but significant impact on cardiometabolic risk factors and PCAD. IL‐6 inhibition with ziltivekimab or canakinumab may benefit high‐risk populations (e.g. brown race population, Caucasians, obese patients, etc.) with rs1800795 to prevent PCAD.

项与 Ziltivekimab 相关的新闻（医药）

2025-01-22

·PRNewswire

Chronic Heart Failure Market to Observe Stunning Growth at a CAGR of 10% by 2034 Owing to Strong Uptake of Entresto and approved SGLT2 Inhibitors along with Emergence of New Class of Therapies | DelveInsight

Several leading classes of therapies are exploring diverse mechanisms of action to treat CHF, including SGLT2 inhibitors, cardiac myosin activators, myeloperoxidase inhibitors, mineralocorticoid receptor antagonists, GLP-1 receptor agonists, cell therapies, and more. This growing focus is expected to drive the chronic heart failure market forward. In summary, the existing blockbuster therapies such as Entresto, recently approved SGLT2 inhibitors, and Soluble guanylate cyclase (sGC) stimulators, along with emerging cell therapies, peptides, monoclonal antibodies, and small molecules, together have the potential to drive the existing market along with securing a significant market share upon introduction of new entrants to the CHF treatment landscape. LAS VEGAS, Jan. 22, 2025 /PRNewswire/ -- DelveInsight's Chronic Heart Failure Market Insights report includes a comprehensive understanding of current treatment practices, chronic heart failure emerging drugs, market share of individual therapies, and current and forecasted market size from 2020 to 2034, segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan]. Key Takeaways from the Chronic Heart Failure Market Report According to DelveInsight's analysis, the market size for chronic heart failure was found to be approximately USD 5.5 billion in the US in 2023. Among the 7MM, the US contributed the largest market share of the total CHF market size and will continue to experience a steep rise in the market size throughout the forecast period. As per DelveInsight's estimate, the total diagnosed prevalent cases of CHF in the 7MM were approximately 20 million in 2023. Heart failure with preserved ejection fraction (HFpEF) contributed to most of the cases. Within class-specific diagnosed prevalence of Heart failure, NYHA class II and class III contribute the maximum. Established chronic heart failure companies with approved therapies in the market are Novartis, Otsuka, Boehringer Ingelheim/Eli Lilly, Bayer/Merck, Amgen/Servier, scPharmaceuticals, and Lexicon Pharmaceuticals/Viatris. In addition, Daiichi Sankyo and American Regent are targeting adult patients with heart failure who are iron deficient. Among all the approved therapies, Novartis and Otsuka's Entresto, approved since 2015 in the US, is still the leading therapy generating more than USD 4 billion in the 7MM in 2023. Among, Eli Lilly's Jardiance and AstraZeneca's Farxiga, both SGLT2 inhibitors, Farxiga is the leading prescribed SGLT2 inhibitor globally by volume Leading chronic heart failure companies developing emerging therapies, such as Cytokinetics, Bayer, Eli Lilly, BioCardia, Mesoblast, Tenax Therapeutics, Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Intra-Cellular Therapies, Cardurion Pharmaceuticals, Rivus Pharmaceuticals, and others are developing novel chronic heart failure drugs that can be available in the chronic heart failure market in the coming years. The promising chronic heart failure therapies in the pipeline include Omecamtiv Mecarbil, KERENDIA (finerenone), Tirzepatide (LY3298176), CardiAMP Cell Therapy, Ziltivekimab (NN6018), REVASCOR (rexlemestrocel-L), Levosimendan (TNX-103), Semaglutide, Balcinrenone (AZD9977) + dapagliflozin, Mitiperstat (AZD4831), Vicadrostat (BI 690517) + Empagliflozin, Cimlanod (CXL-1427/BMS-986231), Lenrispodun (ITI - 214), CRD-740, HU6, and others. In October 2024, Viatris entered into an exclusive licensing agreement with Lexicon Pharmaceuticals for INPEFA (sotagliflozin) in all markets outside of the US and EU. In September 2024, Bayer presented the late-breaking data of Phase III FINE-HEART findings of KERENDIA (finerenone) during a Hot Line session at the European Society of Cardiology (ESC) Congress 2024. In May 2024, Eli Lilly and Company committed an additional USD 5.3 billion manufacturing investment in the company's newest Indiana site to boost API production for tirzepatide and pipeline medicines. AstraZeneca expects the data of the Phase III BalanceD-HF trial of balcinrenone (AZD9977) + dapagliflozin for heart failure in 2025. Discover which therapies are expected to grab the major chronic heart failure market share @ Chronic Heart Failure Market Report Chronic Heart Failure Overview Chronic heart failure is a long-term condition in which the heart's ability to pump blood efficiently is reduced, leading to inadequate circulation of oxygen and nutrients to meet the body's needs. The primary causes of CHF include coronary artery disease, high blood pressure, diabetes, cardiomyopathy, valvular heart disease, and previous heart attacks. Lifestyle factors like obesity, smoking, excessive alcohol consumption, and a sedentary lifestyle can also contribute to its development. The symptoms of CHF vary in severity and may include persistent fatigue, shortness of breath, swelling in the legs, ankles, or abdomen, rapid or irregular heartbeat, and difficulty exercising. Advanced cases can lead to severe fluid retention, wheezing, and an inability to carry out daily activities. Diagnosis typically involves a comprehensive medical history review and a physical examination, followed by tests like an ECG to assess heart rhythm, echocardiography to evaluate heart structure and function, blood tests, chest X-rays, and stress tests. Early diagnosis and management are crucial to improving quality of life and preventing complications. Chronic Heart Failure Epidemiology Segmentation The chronic heart failure epidemiology section provides insights into the historical and current chronic heart failure patient pool and forecasted trends for the 7MM. It helps recognize the causes of current and forecasted patient trends by exploring numerous studies and views of key opinion leaders. The chronic heart failure market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Diagnosed Prevalent Cases of Heart Failure Gender-specific Cases of Heart Failure Ejection Fraction-specific Cases of Heart Failure New York Heart Association (NYHA) Class-specific Cases of Heart Failure Type-specific Cases of Heart Failure Age-specific Cases of Heart Failure Chronic Heart Failure Treatment Market Current treatments for heart failure primarily rely on angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and diuretics. Additional therapies, such as aldosterone antagonists, amiodarone, antiplatelets, anticoagulants, calcium channel blockers, and nitrates, are also utilized in managing the condition. Most treatment regimens involve a combination of therapies, with beta-blockers being among the most commonly prescribed. Among the approved treatments, Novartis' ENTRESTO has emerged as a leading drug in the congestive heart failure market. Initially slow to gain traction, ENTRESTO has become one of Novartis' key growth drivers, with revenue expected to increase in the coming years. Following its approval for use in patients with preserved ejection fraction, ENTRESTO's market presence has grown significantly. However, ENTRESTO faces growing competition. The entry of new drugs, including SGLT2 inhibitors (such as FARXIGA and JARDIANCE) and VERQUVO, poses a challenge to ENTRESTO's dominance. Additionally, Novartis is set to lose ENTRESTO's exclusivity in the United States in 2025, raising the risk of generic competition. The company is actively engaged in several patent lawsuits to protect its position. SGLT2 inhibitors have also gained a foothold in the CHF market. Although FARXIGA and JARDIANCE are established drugs, they are relatively new in this therapeutic area. The outlook for SGLT2 inhibitors in heart failure is promising, but AstraZeneca and Lilly/Boehringer will have limited time to solidify their positions, as FARXIGA's US patent expires in 2025 and JARDIANCE's in 2028. The recently approved SGLT2 inhibitor sotagliflozin may face challenges in capturing market share from these established treatments. To know more about chronic heart failure treatment guidelines, visit @ Chronic Heart Failure Management Chronic Heart Failure Pipeline Therapies and Key Companies Omecamtiv Mecarbil: Cytokinetics KERENDIA (finerenone): Bayer Tirzepatide (LY3298176): Eli Lilly and Company CardiAMP Cell Therapy: BioCardia Ziltivekimab (NN6018): Novo Nordisk REVASCOR (rexlemestrocel-L): Mesoblast Levosimendan (TNX-103): Tenax Therapeutics Semaglutide: Novo Nordisk Balcinrenone (AZD9977) + dapagliflozin: AstraZeneca Mitiperstat (AZD4831): AstraZeneca Vicadrostat (BI 690517) + Empagliflozin: Boehringer Ingelheim Cimlanod (CXL-1427/BMS-986231): Bristol Myers Squibb Lenrispodun (ITI - 214): Intra-Cellular Therapies CRD-740: Cardurion Pharmaceuticals HU6: Rivus Pharmaceuticals Discover more about chronic heart failure drugs in development @ Chronic Heart Failure Clinical Trials Chronic Heart Failure Market Dynamics The chronic heart failure market dynamics are expected to change in the coming years. An increasing prevalence of cardiovascular diseases, fueled by aging populations and lifestyle-related risk factors such as obesity, hypertension, and diabetes, has significantly raised the demand for effective CHF treatments. Advances in medical technology, including innovative drug therapies, cardiac devices, and regenerative medicine, are expanding treatment options and improving patient outcomes. Growing awareness about heart health and early diagnosis, supported by government and non-government initiatives, is also boosting market expansion. Additionally, the rising focus on personalized medicine and the development of therapies targeting the underlying molecular mechanisms of CHF are creating lucrative opportunities. The increasing healthcare expenditure and the availability of reimbursement policies in developed and emerging economies further bolster the market's growth trajectory. Furthermore, potential therapies are being investigated for the treatment of chronic heart failure, and it is safe to predict that the treatment space will significantly impact the chronic heart failure market during the forecast period. Moreover, the anticipated introduction of emerging therapies with improved efficacy and a further improvement in the diagnosis rate are expected to drive the growth of the chronic heart failure market in the 7MM. However several factors may impede the growth of the chronic heart failure market. A key challenge is the underdiagnosis and delayed recognition of CHF due to overlapping symptoms with other conditions and the lack of widespread access to advanced diagnostic tools in many regions. Economic constraints, particularly in low- and middle-income countries, limit patient access to costly therapies, including advanced drugs and devices. Additionally, adherence to treatment regimens remains low due to the complexity of management protocols and the long-term nature of care, leading to suboptimal outcomes. Regulatory hurdles and lengthy approval processes for novel therapies further impede the introduction of innovative treatments. Finally, a limited understanding among general practitioners about newer guidelines and therapies reduces the referral rates to specialists, creating gaps in patient care. Addressing these barriers requires concerted efforts in education, affordability, and healthcare infrastructure. Scope of the Chronic Heart Failure Market Report Therapeutic Assessment: Chronic Heart Failure current marketed and emerging therapies Chronic Heart Failure Market Dynamics: Key Market Forecast Assumptions of Emerging Chronic Heart Failure Drugs and Market Outlook Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's views, Analyst's views, Chronic Heart Failure Market Access and Reimbursement Download the report to understand which factors are driving chronic heart failure market trends @ Chronic Heart Failure Market Trends Table of Contents Related Reports Chronic Heart Failure Epidemiology Forecast Chronic Heart Failure Epidemiology Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology as well as the chronic heart failure epidemiology trends. Chronic Heart Failure Pipeline Chronic Heart Failure Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key CHF companies, including Zensun (Shanghai) Sci & Tech, Cytokinetics, Mesoblast, Shanghai Hongyitang Biopharmaceutical Technology, Tasly Pharmaceuticals, Ionis Pharmaceuticals, Berlin Cures, CardioCell, Help Therapeutics, Eli Lilly and Company, Chong Kun Dang Pharmaceutical, Antlia Biosciences, Cardiol Therapeutics, among others. Acute Coronary Syndrome Market Acute Coronary Syndrome Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key ACS companies, including Novartis, Boehringer Idorsia Pharmaceuticals, Viatris, Recardio, AstraZeneca, Faraday Pharmaceuticals, DalCor Pharmaceuticals, Roche, Jiangsu Vcare PharmaTech, CeleCor Therapeutics, Novo Nordisk, Bristol Myers Squibb, Johnson & Johnson Innovative Medicine, CellProthera, BioCardia, Kancera, Amgen, Arrowhead Pharmaceuticals, Abcentra , among others. Acute Coronary Syndrome Pipeline Acute Coronary Syndrome Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key acute coronary syndrome companies, including Janssen Research & Development, LLC, DalCor Pharmaceuticals, Hyloris Pharmaceuticals, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期上市批准引进/卖出

2024-10-18

·BiG生物创新社

盘点｜自免重磅靶点及研发进展

作者｜小麦目前自免是仅次于肿瘤的第二大市场领域，2022年全球自免药物市场规模约达1323亿美元，据弗若斯特沙利文预测，到2030年，全球自免药物市场规模有望达到1760亿美元，2022~2030年复合年增长率为3.6%。国内在自免领域远远落后于国外，但近几年国内自免药物发展迅速，今年迪哲医药的JAK抑制剂戈利昔替尼、康诺亚生物的IL-4Rα抗体药物司普奇拜单抗、恒瑞医药的靶向IL-17A生物制剂夫那奇珠单抗和智翔金泰的靶向IL-17A生物制剂赛立奇单抗等相继获批上市，有望打破进口药的垄断地位，给患者提供更多的选择。 01 JAK靶向制剂 JAK激酶属于细胞内非受体酪氨酸激酶家族，包括JAK1、JAK2、JAK3、TYK2四个成员，介导细胞因子产生的信号，并通过JAK-STAT信号通路传递下去，参与了免疫、细胞分裂、细胞死亡和肿瘤形成等过程。该通路异常可能导致各种疾病，如皮肤病、癌症和影响免疫系统的疾病等（图1）[1]。图1. JAK家族介导信号通路全球已有十多款JAK抑制剂获批上市，包括第一代的托法替布、芦可替尼、巴瑞替尼、培非替尼和迪高替尼；第二代的菲达替尼、乌帕替尼、非戈替尼、阿布昔替尼和帕瑞替尼以及第三代的氘可来昔替尼等，这些抑制剂大多用于关节炎、特应性皮炎等自免疾病（图2）。图2. 获批和部分在研的JAK抑制剂为了提高竞争力，很多药企开始探索JAK抑制剂的新用途，如辉瑞的利特昔替尼、礼来巴瑞替尼和Concert Pharmaceuticals/Sun Pharmaceuticals的氘代芦可替尼获批斑秃新适应症，迪哲医药的戈利昔替尼获批用于治疗既往至少接受过一线系统性治疗的复发或难治的外周T细胞淋巴瘤（r/r PTCL）成人患者，成为全球首个且唯一获批用于治疗PTCL的JAK1抑制剂。除此之外，还有很多临床在研的JAK抑制剂，如泽璟制药的杰克替尼、恒瑞医药的艾玛昔替尼、辉瑞/Priovant Therapeutics的brepocitinib和再极医药的MAX-40070等，其中杰克替尼和艾玛昔替尼都处于申报上市阶段。 02 IL-4靶向制剂白细胞介素4（IL-4）主要是由T细胞、自然T细胞、肥大细胞和嗜酸性粒细胞产生的一种糖基化的I型细胞因子。 IL-4和IL-13是2型免疫反应中的关键细胞因子，作用于1型 IL-4Rα/γ和/或2型IL-4Rα/IL-13Rα复合物引发其信号传导作用，从而激活JAK-STAT信号通路（图3）。图3. IL-4和IL-13介导的信号通路目前为止全球范围内有5款靶向IL-4R药物获批上市，分别是甲磺司特、度普利尤单抗、吡美莫司、Actimmune以及司普奇拜单抗，其中度普利尤单抗是全球首款获批的IL-4R单抗药物，司普奇拜单抗是国内首个、全球范围第二个申报并获批上市的IL-4Rα抗体药物。图4. 获批和部分在研的靶向IL-4的药物度普利尤单抗是赛诺菲的当家花旦，在自免领域尤其是特应性皮炎适应症上取得巨大成功，撑起特药板块半边天，2023年销售额达到107.15亿欧元（115.7亿美元）。今年7月和9月，度普利尤单抗相继在欧盟、美国和中国获批慢性阻塞性肺病（COPD）新适应症，扩大其适应人群。除此之外，临床上还有很多在研的IL-4/IL-4R抑制剂，如康乃德的CBP-201、康方生物的AK120以及智翔医药的GR-1802等。 03 IL-17靶向制剂白细胞介素17（IL-17）是由CD4+ T细胞分泌，能够诱导上皮细胞、内皮细胞、成纤维细胞合成分泌IL-6、IL-8、G-CSF、PGE2，促进ICAM-1的表达的促炎因子。 IL-17有 IL-17A、IL-17B、IL-17C、IL-17D、IL-17E（也被称为IL-25）和IL-17F 6个家族成员。白介素IL-17受体（IL-17R）有IL-17RA、IL-17RB、IL-17RC、IL-17RD、IL-17RE 5个家族成员（图5）[2]。图5. IL-17介导的信号通路全球范围内共上市7款靶向IL-17A/IL-17RA药物，分别是司库奇尤单抗、依奇珠单抗、尼塔奇单抗、比吉利珠单抗、布罗利尤单抗、夫那奇珠单抗和赛立奇单抗（图6）。图6. 获批和部分在研的靶向IL-17药物目前，司库奇尤单抗和依奇珠单抗是全球最畅销的两款IL-17靶向生物制剂，司库奇尤单抗是由诺华研发的首款获批上市的靶向IL-17A单抗，用于治疗银屑病、银屑病关节炎和强直性脊柱炎等自免疾病，2022年销售额达47.88亿美元，2023年销售额达49.8亿美元。依奇珠单抗是由礼来研发的靶向IL-17A单抗，是第一个在银屑病关节炎（PsA）头对头研究中疗效优于阿达木单抗的IL-17A拮抗剂，2022年销售额达到24.82亿美元，2023年销售额达到27.6亿美元。今年8月份，恒瑞医药的夫那奇珠单抗和智翔金泰的赛立奇单抗获批上市，用于治疗适合接受系统治疗或光疗的中重度斑块状银屑病成人患者，成为国产首批获批的本土自主研发重组抗IL-17A人源化单克隆抗体，将打破同类进口药物的长期垄断局面，为银屑病患者提供新的治疗选择。除此之外，还有很多临床在研的靶向IL-17的生物制剂，包括荃信生物的QX-002N，康方生物的AK-111和君实生物的JS005等。 04 IL-6靶向制剂白介素-6（IL-6）是趋化因子家族的一种细胞因子，主要由单核巨噬细胞、 Th2细胞、血管内皮细胞、成纤维细胞产生。 IL-6的受体蛋白，由特异性的IL-6结合受体蛋白（IL-6R），和被称为信号转导蛋白的gp130所组成。按照信号传导方式的差异，IL-6参与的信号途径，可以分为经典信号通路（classical signaling）和转信号通路（Trans-signaling）。在经典信号通路中，IL-6与其膜结合受体mIL-6R、可溶性受体sIL-6R结合后，招募gp130（一种跨膜蛋白，细胞因子受体）结合形成IL-6-IL-6R-gp130六聚体，触发下游JAK-STAT、RAS-RAF等信号通路转导和基因表达。在转信号通路中，IL-6-sIL-6R复合物与gp130结合，启动细胞内信号转导，促进细胞增殖、分化、氧化应激和免疫调节（图7）[3]。图7. IL-6信号转导和IL-6受体系统的模式 IL-6信号通路异常与很多疾病的发病机制有关，包括类风湿性关节炎（RA）、系统性幼年特发性关节炎(sJIA)、Castleman病、巨细胞动脉炎（GCA）、大动脉炎和细胞因子释放综合征（CRS）等。目前全球有4款药物获批上市，包括靶向IL-6R的托珠单抗、Sarilumab、和萨特利珠单抗以及靶向IL-6的司妥昔单抗，其中托珠单抗由于上市时间早应用广泛，销售额遥遥领先，受益于用于新冠治疗的获批，曾在2021年达到销售峰值39.6亿美元。图8. 部分靶向IL-6的药物除此之外，临床上还有很多在研的IL-6或IL-6R拮抗剂药物，为了提高竞争性，很多药企进行差异化布局，开发新的适应症，包括优时比的olokizumab、诺和诺德的ziltivekimab和罗氏的RG6179等（图6）。 Olokizumab最初由优时比公司研发，是一款靶向IL-6的人源化单抗。后来在2013年转让给了俄罗斯药企R-Pharm，目前正在进行RA领域的上市申请。 Ziltivekimab最初是由Corvidia Therapeutics研发的IL-6单抗药物，后于2020年6月，诺和诺德以21亿美元收购Corvidia Therapeutics，接管了其主要候选药物ziltivekimab的开发工作。 Ziltivekimab旨在阻断IL-6通路来降低全身炎症，从而降低动脉粥样硬化性心血管疾病（ASCVD）和慢性肾脏病（CKD）患者的主要心血管不良事件风险，具有延长的半衰期，可以通过每月一次皮下注射给药。 RG6179是由罗氏研发的IgG2类IL-6单抗，可阻断经典和转信号传导，用于糖尿病性黄斑水肿、自身炎症性疾病、黄斑水肿和葡萄膜性黄斑水肿。小结自免是一个很大的疾病领域，有很多疾病靶点，目前全球自身免疫病药物市场中，TNF-α和IL-12/IL-23两个自免领域老靶点抑制剂销售额仍位居前列，而JAK、IL-4R、IL-17A、IL-6、IL-5、URAT1、TSLP、MASP-2、TYK2等靶点，则吸引较多创新药企布局，本文主要介绍JAK、IL-4R、IL-17A和IL-6四个热门自免靶点及其研发进展。参考文献 1.Aikaterini Tsiogka et.al, The JAK/STAT Pathway and Its Selective Inhibition in the Treatment of Atopic Dermatitis: A Systematic Review, J. Clin. Med. 2022, 11, 4431 2.Mandy J. McGeachy, Daniel J. Cua, and Sarah L. Gaffen, The IL-17 Family of Cytokines in Health and Disease, Immunity 50, April 16, 2019 3.Masashi Narazaki and Tadamitsu Kishimoto, The Two-Faced Cytokine IL-6 in Host Defense and Diseases, Int. J. Mol. Sci. 2018, 19, 3528. BiG近期会议 10月26日，第三届生物计算大会保留栏目-第二届吐槽大会即将再度来袭！将围绕投融资、行业心态、年轻人，及AI等热门话题展开策划，通过移幕换景，大咖带新秀，一同探讨AI+Biomed的融合之道！ ▼ 10月31日，BiG联合Citeline，将于10月底，举办自免小规模私董研讨会，聚焦：TCE vs. CAR-T，自身免疫开发策略，线上同步直播，敬请期待！ ▼ 共建Biomedical创新生态圈！如何加入BiG会员？

上市批准免疫疗法细胞疗法

2024-08-10

·行舟Drug

延缓慢性肾脏病进展药物临床试验的关键设计考虑

点击上方的行舟Drug ▲ 添加关注延缓慢性肾脏病进展药物临床试验的关键设计考虑来源《中国药学杂志》2024年作者李杰静，王娜，唐崇淇，王水强，谢松梅国家药品监督管理局药品审评中心摘要目的：探讨延缓慢性肾脏病进展药物的临床试验设计的关键技术考虑。方法：通过系统调研国内外文献，结合疾病特点、药物研发和审评实践，对延缓慢性肾脏病进展的药物临床试验关键要素的设计提出技术建议。结果：临床试验总体设计建议采用随机、双盲、安慰剂/标准治疗为对照的设计。研究人群应能反映预期试验目标的广泛的人群，入选标准及疗效评价需同时考虑病因、分期、疾病进展风险因素及合并治疗等方面。主要疗效终点推荐临床终点事件的复合终点，早期或进展缓慢的慢性肾脏病可选择肾小球滤过率平均变化率作为主要疗效终点。安全性评价指标除遵循一般共性标准外，需关注并识别与研究药物有关的安全性问题，并与自然病程进展有关的安全性信号加以鉴别，另外还应对原基础疾病设定相应的安全性评价指标。关键词慢性肾脏病；药物临床试验设计 _ 正文 _ 慢性肾脏病（chronic kidney disease，CKD）是指各种原因引起的肾脏结构或功能异常超过3个月或以上，并对健康造成影响的一类疾病，其诊断标准为发生肾损害或肾小球滤过率（glomerular filtration rate，GFR）低于60mL･min-1･1.73m-2，其中肾损害包括蛋白尿、尿沉渣异常、肾小管功能障碍引起的电解质及其他异常、肾脏组织学或影像学检查异常、肾移植病史。依据改善全球肾脏病预后组织临床实践指南，慢性肾脏病根据病因、肾小球滤过率和白蛋白尿程度进行分类和分期。慢性肾脏病的发病率和死亡率逐年升高，已经成为严重影响民众生命健康的公共卫生问题。据统计，中国慢性肾脏病患病率约为10.8%。治疗慢性肾脏病的主要目的是减慢肾小球滤过率下降的速率、延迟终末期肾病和主要的并发症（如心血管并发症等）的发生。近年来国内外虽有多家企业针对慢性肾脏病适应证进行药物研发，但目前仅有达格列净片和非奈利酮片获批用于该适应证，临床仍缺乏安全有效的延缓慢性肾脏病进展的药物。本文参考国外相关药物临床试验技术指导原则和国内慢性肾脏病相关诊治专家共识等，结合审评工作实践、疾病特点和药物研发进展，探讨该领域药物临床试验设计等方面的关注点，以期为国内开展此类新药临床试验设计提供有益参考。 1 我国已上市及在研药物临床试验概况 1.1 已上市药品目前，我国仅有两款药品批准用于治疗慢性肾脏病，分别为达格列净片和非奈利酮片。其中，达格列净片批准的适应证为：用于慢性肾脏病成人患者，降低有进展风险的慢性肾脏病成人患者估算的肾小球滤过率（estimated glomerular filtration rate，eGFR）持续下降、终末期肾病、心血管死亡和因心力衰竭而住院的风险。非奈利酮片批准的适应证为：本品用于与2型糖尿病相关的慢性肾脏病成人患者（伴白蛋白尿），以降低eGFR持续下降、终末期肾病、心血管死亡和因心力衰竭住院的风险。达格列净是一种高效、选择性、可逆的钠-葡萄糖共转运体2（sodium-glucose co-transporter 2，SGLT2）抑制剂，可通过降低肾小球压力、减轻炎症/纤维化等作用，发挥改善CKD患者临床结局的作用。既往批准用于治疗2型糖尿病和心衰，在一项国际、多中心、随机、双盲、安慰剂对照临床试验（DAPA-CKD）中，评价了达格列净对慢性肾脏病患者的肾脏结局和心血管死亡的影响。该项临床试验入选了4304例进展风险较高的相对晚期接受标准治疗的CKD人群，按1: 1随机分配至达格列净组或安慰剂组，研究至末次访视的中位时间为28.5个月。最常见的CKD病因依次是糖尿病肾病、缺血性/高血压肾病和IgA肾病。研究主要目的是明确达格列净是否可降低复合终点，即eGFR持续下降≥50%、进展至终末期肾病（end-stage renal disease，ESRD）（定义为持续eGFR<15mL･min-1･1.73m-2，开始长期透析治疗或肾移植）、心血管或肾病死亡的发生率。非奈利酮是非甾体选择性盐皮质激素受体拮抗剂，其可通过减轻盐皮质激素受体过度激活介导的炎症和纤维化而发挥作用。一项在慢性肾病伴2型糖尿病的患者中进行的随机、双盲、安慰剂对照、多中心临床试验（FIDELIO-DKD）中，共有5674例患者随机接受非奈利酮或安慰剂治疗，非奈利酮组和安慰剂组总观察时间的中位时间分别为31.737和31.704个月。研究旨在确定非奈利酮是否可降低eGFR较基线值持续下降≥40%、肾衰竭（定义为慢性透析、肾移植或eGFR持续降低至<15mL･min-1･1.73m-2）或肾性死亡的发生率。 1.2 在研药物目前丹麦诺和诺德公司研发的ziltivekimab注射液已获准在我国开展慢性肾脏病临床试验。ziltivekimab是一种全人源化单克隆抗体，靶向作用于白细胞介素6（interleukin-6，IL-6），拟通过直接抑制IL-6减少系统性炎症，降低动脉硬化性心血管疾病合并慢性肾脏疾病中残余炎症风险，从而降低心血管事件复发风险。目前其临床试验正在进行中。其Ⅲ期临床试验为一项在确诊动脉粥样硬化性心血管疾病合并CKD和系统性炎症的患者中进行的干预性、随机、平行组、双盲、安慰剂对照、国际多中心临床试验，患者在标准治疗的基础上接受ziltivekimab或安慰剂治疗，主要疗效终点为从随机到首次出现主要心血管不良事件时间的复合终点，复合终点事件包括：心血管死亡、非致死性心肌梗死或非致死性卒中，预期研究持续时间为首例受试者随机后不超过48个月。文章内容由凡默谷小编查阅文献选取，排版与编辑为原创。如转载，请尊重劳动成果，注明【来源：凡默谷公众号】。 2 临床试验设计 2.1 临床药理学研究应根据慢性肾脏病的不同病因和研究新药的特点，进行包括药物相互作用等方面的临床药理学方案设计。通常需要评价临床实践中可能的合并用药对有效性和安全性的影响。另外，需根据新药的研发目标，参考《肾功能不全患者药代动力学研究技术指导原则》，选择适当的慢性肾脏病分期患者人群，初步了解药物在慢性肾脏病患者中的药动学和安全性特征，阐明药物的剂量-暴露量-效应关系，为后续临床试验中选择合理的给药方案及剂量调整提供依据。如研究新药为生物制品，应关注药物的免疫原性及其对安全性与有效性的影响。鼓励根据慢性肾脏病病因与药物作用机制，采用适宜的生物标志物作为药效学相关标志物，更好地评价药物有效性和安全性。 2.2 探索性临床试验探索性临床试验建议采用在背景治疗基础上的安慰剂对照试验设计，同时应考虑不同慢性肾脏病分期患者药代特征的差异，合理设计量效关系研究。剂量探索研究最好采用平行、固定剂量组设计，应设置足够剂量组以供充分评价。探索性临床试验的主要疗效终点可参考确证性临床试验的主要疗效终点，还可选择其他探索性疗效终点，实测肾小球滤过率（measured glomerular filtration rate，mGFR）或eGFR也适用于探索性试验。其他特定生物标志物，包括显著降低慢性肾脏病患者蛋白尿程度，也是探索性临床试验目的的合理选择，或可作为相对短期临床试验中的支持性疗效终点。 2.3 确证性临床试验 2.3.1 总体设计慢性肾脏病的病因较多，不同病因导致的慢性肾脏病的发病机制、病理生理、组织学变化不同。在开发慢性肾脏病治疗药物时，建议根据新药的作用机制及研发目的，选择特定病因的慢性肾脏病人群进行确证性临床试验。确证性临床试验建议采用多中心、随机、双盲、平行对照试验设计。慢性肾脏病病情和治疗方案较为复杂，应在标准治疗的基础上进行研究。如研究药物可替代延缓慢性肾脏病进展的既定治疗方案中的一种或几种治疗，从而改善有效性、安全性或依从性，可采取优效或非劣效设计；抑或研究药物可作为在标准治疗基础上的叠加治疗，提高既定治疗方案的有效性，则应采取安慰剂对照优效性设计。如果采用非劣效试验设计，非劣效界值应遵循相关指导原则预先确定，并与监管机构达成一致。应在试验设计时即对肾脏疾病的病因等相关因素进行预先定义，考虑适当分层随机，以保证组间基线均衡可比。 2.3.2 研究人群选择慢性肾脏病的病因多种多样，对慢性肾脏病的治疗也应是包括病因治疗在内的综合治疗方案。因此，在临床试验中除考虑纳入能反映预期目标的广泛的目标人群外，还应从患者病因、可能导致疾病进展的风险因素以及合并治疗等多方面，充分考虑各种混杂因素对试验结果评价的影响。引起慢性肾脏病的病因包括糖尿病、高血压、慢性肾小球肾炎、慢性肾小管间质性肾炎、慢性肾盂肾炎或遗传性肾脏病等。可能导致慢性肾脏病疾病进展的风险因素包括：如高龄、家族史等方面的易感因素；直接引发肾损害的疾病或药物的引发因素；导致肾损害恶化的进展因素。合并治疗包括控制血糖、控制血压等在内的对慢性肾脏病的病因治疗等。需通过实验室检查和临床表现来确定慢性肾脏病的诊断及分期等，以确保入选人群可代表目标适应证人群。应详细记录每例患者的肾脏疾病的病因、分期、临床表现、合并症、并发症、合并用药以及与慢性肾脏病进展相关的风险因素等信息。另外，还应聚焦国内慢性肾脏病疾病领域的临床需求，综合考虑试验的科学性和可行性，以及临床试验研究人群对目标适应证的代表性。多中心临床试验中入组受试者可能受不同地区特定政策和临床实践（例如不同地区医生对患者开始肾脏替代治疗的时机存在不同标准）的影响。因此，应充分考虑该研究中心入组患者的代表性和试验设计（例如分层随机）的影响。 2.3.3 疗效指标及评价慢性肾脏病由多种病因引起，是异质性强的一组疾病，具有不同程度的肾功能受损、蛋白尿等临床表现。除终点事件代表慢性肾脏病患者的临床结局外，肾小球滤过率是公认的评价肾脏功能的最重要指标。蛋白尿是衡量部分慢性肾脏病包括IgA肾病等肾脏疾病严重程度的重要指标。因此，在设置终点指标时，应基于新药作用机制、治疗学目标、疾病严重程度等方面进行综合考虑。临床终点事件是反映受试者肾功能变化、存活时间等的特征性变量，故建议首选“至发生临床终点事件的时间”或“临床终点事件的发生率”作为主要疗效终点。如果是晚期或快速进展的疾病，应考虑将全因死亡作为临床终点的一部分。如果预期死亡事件发生率非常低，则可考虑将比较两组死亡率作为关键的次要疗效终点。肾小球滤过率能够客观地测量或评价肾功能，是公认的可代表肾脏功能的最重要的客观测量指标。在以早期慢性肾脏病（例如慢性肾脏病1期或2期）或进展缓慢的慢性肾脏病患者为研究对象的临床试验中，可采用肾小球滤过率平均变化率作为主要疗效终点，通常根据基线至治疗期末肾小球滤过率的平均变化率评估药物疗效。慢性肾脏病进展通常比较缓慢，为了获得足够的终点事件，临床试验往往需要大样本、数年至数十年的随访时间。为了实施高质量、科学且能够满足临床需求的药物临床试验，将蛋白尿和/或白蛋白尿改变作为肾脏疾病研究中临床终点事件或肾小球滤过率的替代指标可减少研究样本量并缩短研发周期，但其科学性却尚缺乏证据支持。两项荟萃分析提示在伴有蛋白尿的肾病临床研究中，6~24个月内尿白蛋白/肌酐比值（或尿蛋白与肌酐比值）自基线下降30%可作为替代指标。但如果受试者基线蛋白尿水平不同，将蛋白尿的变化百分比作为替代终点则不够科学。此外，残余蛋白尿对肾脏的影响如何等诸多问题仍然需要更多的研究进一步论证。因此，尚缺乏充分证据显示尿蛋白程度与慢性肾脏病预后的相关性，故该指标目前仅作为支持有效性评价的次要疗效指标。另外，由于临床治疗决策的差异（例如医生对开始透析的时间标准不同）可能会对主要疗效终点的评价产生影响，因此应计划进行敏感性分析。试验设计时应计划对试验结果进行额外评价，例如，独立盲态审查员应按照预先定义的规则评估开放性试验的结果。如果独立盲态审查员之间未达成一致，则应由集中盲态小组进行裁定。 2.3.4 对照的选择对照药及其剂量的选择将取决于拟定适应证、慢性肾脏病的病因及病理类型和肾脏病进展的危险因素等。不同临床试验入选人群的基线疾病严重程度以及评价有效性的指标可能不同，应根据药物研发目的选择合理的对照药物。安慰剂对照试验旨在评估试验药物的绝对疗效，阳性对照设计旨在证明试验药物优于或非劣于对照药物。通常，首先选择已批准的相同适应证的药品作为阳性对照，通过试验证明试验药物疗效方面与阳性对照相同，或优于阳性对照。其次，如临床标准治疗方案为包含未获批该适应证的药物的治疗方案时，应选择最佳的标准治疗方案作为阳性对照。 2.3.5 合并治疗由于慢性肾脏病基础病因多种多样，对受试者基础疾病如高血压、糖尿病等的治疗同样重要，因此受试者可能存在多种合并用药，应在临床试验设计时予以充分考虑。应预先在临床试验方案中对合并治疗进行明确规定，合并治疗应尽可能标准化、保持稳定，同时尽可能保持组间均衡，以减少合并治疗对试验药物安全有效性的评价产生的影响。 2.3.6 治疗持续时间临床试验中通常应根据受试者基线慢性肾脏病分期、疾病进展情况、药物作用强度、临床试验目的、主要疗效终点等确定治疗持续时间。因此，在以临床终点事件为主要疗效终点的事件驱动试验中，治疗持续时间取决于预先设定的需要收集的事件数量。对以肾小球滤过率平均变化率为主要疗效终点的临床试验，需根据基线至治疗结束时肾小球滤过率的总斜率变化以评价药物疗效，建议至少治疗并观察24个月以评估肾小球滤过率的下降速率。 2.3.7 安全性评价指标慢性肾脏病需要根据患者疾病进展情况，可能采取长期甚至终身药物治疗。故需要有足够的暴露量和暴露时间进行安全性观察，应符合ICH E1指导原则要求。评价指标原则上遵循安全性评价的共性标准，应常规收集记录治疗中出现的不良事件、临床实验室检查结果和生命体征测量结果以评估安全性。如果受试者在随访期间肾功能突然下降，应通过全面评估明确其发生原因、诱发因素及转归，需慎重分析肾功能突然下降与试验药物的相互关系。应注意收集相关数据，分析治疗过程中肾功能突然下降的发生原因及转归。临床试验中应根据药物作用机制、非临床研究及前期临床试验中发现的潜在安全性问题，需首先关注并识别可能与研究药物有关的肾脏安全性问题。其次，肾脏疾病与基础疾病特别是心血管疾病等可能相关，因此还应对原基础疾病设定相应的安全性评价指标。再次，慢性肾脏病的自然病程和临床试验中使用的药物可能导致出现相同的安全性信号，应针对这些信号加以鉴别。 3 结语近年来，随着人口老龄化程度加剧等，慢性肾脏病的发病率和死亡率逐年升高，已经成为严重影响民众生命健康的公共卫生问题。大多数肾小球疾病进展缓慢，在疾病早期可发现尿液检验异常，较多患者的肾功能在10年内可保持正常，对患者的早期治疗能够推迟终末期肾病的发生。如果早期即对患者进行医学干预，将对患者工作生活、经济负担以及生命质量等方面带来非常大的益处。另外，目前对晚期慢性肾脏病患者的治疗药物仍比较有限。因此，对延缓慢性肾脏病进展的药物，存在迫切的临床需求。目前国内外已有多家企业针对慢性肾脏病开展了药物研发。本文结合已上市新药研发经验、相关指南以及对疾病特点、治疗需求等方面，对慢性肾脏病临床试验总体设计等方面提出一些考虑。由于慢性肾脏病的基础病因复杂多样，因此在研发早期阶段，即应根据药物作用机制特点和最终研发目的，进行探索和验证，进而为确证性临床试验设计提供参考。也正是由于研究人群基础病因、合并治疗等方面的复杂性，如何纳入具有代表性的研究人群并保持组间基线特征及合并治疗的均衡，以尽量降低混杂因素对试验结果评价的影响，同样需要重点关注。另外，疗效终点指标的选择以及治疗持续时间，同样需要基于疾病特点和药物作用机制等，进行合理设置。以上观点可能随着基础研究的不断深入，有效药物研发上市等情况而发生变化。例如是否会有与临床结局相关性更强的替代指标，尚需要进一步发掘、探索和验证。期望本文能够为我国工业界和临床研究者在国内相关领域药物临床研发和评价中提供有益技术参考，进而有助于开发出更多更好的新药满足患者临床需求。参考文献详见《中国药学杂志》2024年文章信息源于公众号凡默谷，登载该文章目的为更广泛的传递行业信息，不代表赞同其观点或对其真实性负责。文章版权归原作者及原出处所有，文章内容仅供参考。本网拥有对此声明的最终解释权，若无意侵犯版权，请联系小编删除。学如逆水行舟，不进则退；心似平原走马，易放难收。行舟Drug 每日更新欢迎订阅+ 医药大数据|行业动态|政策解读

临床研究

100 项与 Ziltivekimab 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
急性心肌梗塞	临床3期	美国	Novo Nordisk A/S	2024-06-25
急性心肌梗塞	临床3期	中国	Novo Nordisk A/S	2024-06-25
急性心肌梗塞	临床3期	日本	Novo Nordisk A/S	2024-06-25
急性心肌梗塞	临床3期	阿根廷	Novo Nordisk A/S	2024-06-25
急性心肌梗塞	临床3期	澳大利亚	Novo Nordisk A/S	2024-06-25
急性心肌梗塞	临床3期	巴西	Novo Nordisk A/S	2024-06-25
急性心肌梗塞	临床3期	保加利亚	Novo Nordisk A/S	2024-06-25
急性心肌梗塞	临床3期	加拿大	Novo Nordisk A/S	2024-06-25
急性心肌梗塞	临床3期	捷克	Novo Nordisk A/S	2024-06-25
急性心肌梗塞	临床3期	丹麦	Novo Nordisk A/S	2024-06-25

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临床结果

适应症

分期

评价

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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


NCT03926117 (RESCUE, Pubmed) 人工标引	临床2期	炎症 \| 慢性肾病 C-reactive Protein Expression	261	Ziltivekimab 7.5 mg	壓廠願鹽鏇艱顧餘廠顧(蓋鑰選鹽餘繭築鏇醖構) = 廠鑰廠鏇襯選鑰窪觸齋鹽選觸淵觸齋艱鑰製選 (築積鑰範壓壓顧積選遞 )	积极	2024-01-01
				Ziltivekimab 15 mg	壓廠願鹽鏇艱顧餘廠顧(蓋鑰選鹽餘繭築鏇醖構) = 網夢廠選繭遞積積選醖鹽選觸淵觸齋艱鑰製選 (築積鑰範壓壓顧積選遞 )
NCT03926117 (RESCUE \| RESCUE Trial, CTgov)	临床2期	炎症 \| 慢性肾病	264	Ziltivekimab (Placebo)	襯範簾觸糧繭製廠構憲(艱鬱淵選製夢糧繭觸艱) = 糧醖餘鹽繭鑰糧鹹膚壓夢選簾積構壓願艱淵淵 (積獵積齋衊觸鬱構廠顧, 願獵願憲繭遞糧觸築鏇 ~ 選齋襯顧艱壓鑰簾夢蓋) 更多	-	2023-08-09
				Ziltivekimab (Ziltivekimab 7.5 mg)	襯範簾觸糧繭製廠構憲(艱鬱淵選製夢糧繭觸艱) = 餘觸蓋願鏇鬱壓選鹽窪夢選簾積構壓願艱淵淵 (積獵積齋衊觸鬱構廠顧, 鏇鑰襯積壓窪窪廠願衊 ~ 願鹽廠醖壓蓋淵膚蓋糧) 更多
NCT03926117 (RESCUE Trial, ASN2021)	临床2期	慢性肾病 serum hemoglobin \| iron homeostasis \| high-sensitivity C-reactive protein	-	Ziltivekimab 7.5 mg	壓壓鹽醖憲鹹鏇鑰繭鹹(鹽顧壓遞窪艱鹹簾製簾) = 壓獵艱壓糧獵簾遞築襯製鏇網製積廠願願膚淵 (醖膚艱遞鏇蓋鏇膚鬱廠 )	积极	2021-10-27
				Ziltivekimab 15 mg	壓壓鹽醖憲鹹鏇鑰繭鹹(鹽顧壓遞窪艱鹹簾製簾) = 醖遞艱顧遞鑰廠糧顧顧製鏇網製積廠願願膚淵 (醖膚艱遞鏇蓋鏇膚鬱廠 )
NCT02868229 (CTgov)	临床1/2期	贫血	61	Placebo (Placebo)	積齋顧鏇蓋艱繭顧選範 = 艱網壓襯觸積製範膚壓選蓋顧網廠窪醖鹹鑰襯 (範獵構鹹繭簾獵範糧壓, 簾憲膚構範鬱選顧齋構 ~ 夢製餘積廠製廠糧膚鏇) 更多	-	2021-07-30
				COR-001 (COR-001)	醖願窪構範繭構繭選廠(簾遞餘膚積範網鬱獵鏇) = 壓夢齋獵顧鏇鏇獵蓋窪壓構鹽範製窪積製簾簾 (衊製齋簾網鑰範鏇壓鑰, 顧築膚齋衊夢廠顧醖簾 ~ 夢繭餘獵顧艱網構餘築)
NCT03926117 (RESCUE, Pubmed \| Lancet)	临床2期	动脉粥样硬化	264	Placebo	糧鬱鬱艱遞襯積衊顧壓(願願積蓋夢構繭淵夢艱) = 鬱繭淵壓範遞範醖糧窪醖鹽遞醖廠鏇鏇觸範壓 (鏇夢鏇憲鏇膚築鬱窪觸 )	积极	2021-05-14
ASN2019	临床1期	慢性肾病	12	COR-001 5 mg	膚餘膚夢積網艱襯膚鹹(鹽築憲鏇蓋願遞觸醖壓) = 繭淵醖憲網鑰衊選遞膚網獵網憲願築繭膚鏇鬱 (鹹醖簾獵衊齋築餘網蓋 )	积极	2019-11-05
				COR-001 15 mg	膚餘膚夢積網艱襯膚鹹(鹽築憲鏇蓋願遞觸醖壓) = 鏇艱夢獵壓衊願艱鏇構網獵網憲願築繭膚鏇鬱 (鹹醖簾獵衊齋築餘網蓋 )