Ziltivekimab is an

investigational new drug The United States Food and Drug Administration's Investigational New Drug (IND) program is the means by which a pharmaceutical industry, pharmaceutical company obtains permission to start human clinical trials and to ship an experimental drug inte ...

being developed by

Novo Nordisk Novo Nordisk A/S is a Danish multinational pharmaceutical company headquartered in Bagsværd, with production facilities in nine countries and affiliates or offices in five. Novo Nordisk is controlled by majority shareholder Novo Holdings A/S ...

for the treatment of various

inflammatory disease Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants. The five cardinal signs are heat, pain, redness, swelling, and Functio laesa, loss of funct ...

s. It is a fully human

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

that targets

interleukin 6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smoo ...

(IL-6). Ziltivekimab is under investigation for its potential to reduce inflammation in conditions such as

cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...

chronic kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

(CKD),

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

with preserved or mildly reduced

ejection fraction An ejection fraction (EF) is the volumetric fraction (or portion of the total) of fluid (usually blood) ejected from a chamber (usually the heart) with each contraction (or heartbeat). It can refer to the cardiac atrium, cardiac ventricle, gall ...

(HFpEF/HFmrEF), and anemia of inflammation. Administered

subcutaneously The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, or superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and m ...

intravenously Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

, ziltivekimab has demonstrated potential in clinical trials by lowering inflammatory

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

s such as high-sensitivity

C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin ...

(hsCRP) and improving anemia-related parameters in CKD patients. 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.

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 Chronic systemic inflammation is the result of release of pro-inflammatory cytokines from immune-related cells and the chronic activation of the innate immune system. It can contribute to the development or progression of certain conditions such ...

, as measured by biomarkers like hsCRP, serum amyloid A, and

fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...

, which are linked to adverse outcomes in these conditions. In CKD, ailtivekimab has shown potential to improve anemia by reducing IL-6-mediated

hepcidin Hepcidin is a protein that in humans is encoded by the ''HAMP'' gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals. During conditions in which the hepcidin level is abnormally high, such as inflammation, se ...

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 A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

or with

atherosclerotic Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by elev ...

disease. As of May 2025, it is not approved for any indication and is limited to clinical trial settings.

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. By neutralizing IL-6, it reduces the production of acute-phase reactants like hsCRP, serum amyloid A, and fibrinogen, which contribute to systemic inflammation. In CKD, Ziltivekimab lowers hepcidin levels, improving iron metabolism and alleviating anemia of inflammation. Its targeted IL-6 inhibition distinguishes it from IL-6 receptor blockers like tocilizumab, potentially offering a different safety profile with fewer immunosuppressive effects.

Clinical trials

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.

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. 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.

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. 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. 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. Both trials are ongoing , and results have not yet been published.

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.

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.

References

{{reflist Experimental monoclonal antibodies Anti-interleukin monoclonal antibodies