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Ziltivekimab
Antibody against interleukin 6 From Wikipedia, the free encyclopedia
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Ziltivekimab is an investigational new drug being developed by Novo Nordisk for the treatment of various inflammatory diseases. It is a fully human monoclonal antibody that targets interleukin 6 (IL-6). Ziltivekimab is under investigation for its potential to reduce inflammation in conditions such as cardiovascular disease,[1] chronic kidney disease (CKD),[2] heart failure[3] with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF),[1] and anemia of inflammation.[3]
Administered subcutaneously or intravenously, ziltivekimab has demonstrated potential in clinical trials by lowering inflammatory biomarkers such as high-sensitivity C-reactive protein (hsCRP) and improving anemia-related parameters in CKD patients.[4][5]
As of May 2025, ziltivekimab remains investigational and has not been approved for clinical use. It is currently being evaluated in ongoing phase 2 and phase 3 clinical trials.[6]
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Medical use
Ziltivekimab is being developed to manage inflammatory conditions associated with elevated IL-6 levels, including cardiovascular disease, CKD, heart failure (HFpEF/HFmrEF), and anemia of inflammation. It aims to reduce systemic inflammation, as measured by biomarkers like hsCRP, serum amyloid A, and fibrinogen, which are linked to adverse outcomes in these conditions.[7][8]
In CKD, ailtivekimab has shown potential to improve anemia by reducing IL-6-mediated hepcidin expression, decreasing reliance on erythropoiesis-stimulating agents (ESAs). It is also under investigation for reducing cardiovascular events in high-risk patients, such as those post-myocardial infarction or with atherosclerotic disease. As of May 2025, it is not approved for any indication and is limited to clinical trial settings.[7]
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Mechanism of action
Ziltivekimab is a human IgG1, κ monoclonal antibody that binds to the IL-6 ligand, preventing its interaction with the IL-6 receptor and inhibiting downstream inflammatory signaling.[9][10] By neutralizing IL-6, it reduces the production of acute-phase reactants like hsCRP, serum amyloid A, and fibrinogen, which contribute to systemic inflammation.[11]
In CKD, Ziltivekimab lowers hepcidin levels, improving iron metabolism and alleviating anemia of inflammation.[12] Its targeted IL-6 inhibition distinguishes it from IL-6 receptor blockers like tocilizumab, potentially offering a different safety profile with fewer immunosuppressive effects.[11]
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Clinical trials
Summarize
Perspective
Phase 1/2 trial in hemodialysis Ppatients
A phase 1/2, randomized, double-blind, placebo-controlled trial (NCT02868229) evaluated Ziltivekimab in 61 hemodialysis patients with chronic kidney disease (CKD), elevated interleukin-6 (≥4 pg/mL), and a TMPRSS6 gene polymorphism (rs855791) associated with IL-6–mediated inflammation. Patients received placebo or Ziltivekimab (2, 6, or 20 mg) intravenously every two weeks for 12 weeks. The trial assessed safety, pharmacokinetics, and pharmacodynamic endpoints, including inflammatory markers, iron parameters, and erythropoiesis-stimulating agent (ESA) usage.[13]
RESCUE trial
The phase 2 RESCUE trial (NCT03926117) was a double-blind, randomized, placebo-controlled study that enrolled 264 patients with CKD stage 3–5 and high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L.[14] Patients received placebo or subcutaneous Ziltivekimab (7.5, 15, or 30 mg) every four weeks for up to 24 weeks. The trial evaluated changes in hsCRP, hemoglobin levels, iron metabolism biomarkers, and safety outcomes.[15]
RESCUE-2 trial
The RESCUE-2 trial (NCT04626505), a phase 2, randomized, double-blind study in Japan, enrolled 36 adults with CKD stage 3–5 and hsCRP ≥2 mg/L.[16] Participants received placebo or Ziltivekimab (15 or 30 mg) subcutaneously at weeks 0, 4, and 8. The study assessed changes in hsCRP, serum amyloid A, fibrinogen, lipid profiles, and treatment-emergent adverse events.
HERMES and ZEUS Trrials
The ongoing HERMES trial (NCT05636176) is evaluating monthly subcutaneous Ziltivekimab (15 mg) versus placebo in patients with heart failure with preserved or mildly reduced ejection fraction (HFpEF or HFmrEF). The primary endpoints include cardiovascular death, heart failure hospitalization, and urgent visits.[7][17]
The ZEUS trial (NCT05021835), a phase 3 study, is assessing Ziltivekimab's effects on cardiovascular outcomes—including myocardial infarction and stroke—in patients with established cardiovascular disease, CKD, and hsCRP ≥2 mg/L.[18] Both trials are ongoing as of May 2025[update], and results have not yet been published.
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Safety and side effects
Ziltivekimab has been well-tolerated in trials, with no dose-limiting toxicities reported. In the phase 1/2 hemodialysis trial, four treatment-emergent deaths occurred, but no clear causal link to Ziltivekimab was established. The RESCUE and RESCUE-2 trials reported no significant increases in thrombocytopenia, neutropenia, or infections compared to placebo, unlike other IL-6 inhibitors like tocilizumab. A small, statistically significant increase in triglycerides was noted in RESCUE-2, but cholesterol profiles remained unaffected.[citation needed]
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History and legal status
Ziltivekimab was initially developed by Corvidia Therapeutics and later acquired by Novo Nordisk, and is in phase 2 and 3 trials for cardiovascular disease, CKD, and heart failure.[citation needed]
See also
References
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