ziltivekimab (COR-001) / Novo Nordisk - LARVOL DELTA

Seeking and treating inflammation in ischaemic heart disease: are we ready? (PubMed, Eur Heart J Suppl) - "However, the evidence of colchicine's efficacy in this context remains conflicting and inconclusive. In addition, using new systemic markers (IL-6) and modern non-invasive CT or CT-PET imaging techniques will lead to better accuracy in the diagnosis of inflammation, not only systemic but also organ- and lesion-specific."

Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Heart Failure • Inflammation • CRP • IL6

ZEUS - A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With Cardiovascular Disease, Chronic Kidney Disease and Inflammation (clinicaltrials.gov) - P3 | N=6200 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Recruiting ➔ Active, not recruiting | Trial completion date: Jan 2026 ➔ Oct 2026

Enrollment closed • Trial completion date • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Inflammation • Nephrology • Renal Disease • CRP

Inflammation in atherosclerotic cardiovascular disease: From diagnosis to treatment. (PubMed, Eur J Clin Invest) - "Thus, the integration of interventions aimed at lowering the inflammatory burden in combination with aggressive lipid-modifying therapy in secondary prevention may hold the potential to further reduce the still substantial burden of ASCVD."

Journal • Review • Atherosclerosis • Cardiovascular • Inflammation • CRP • IL6

A Research Study of How the Medicine Ziltivekimab Works in the Body of Chinese Men and Women With Kidney Disease and Inflammation (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed | Trial completion date: May 2024 ➔ Sep 2024

Trial completion • Trial completion date • Chronic Kidney Disease • Inflammation • Nephrology • Renal Disease • CRP

Design of the ZEUS Trial: Interleukin-6 Inhibition With Ziltivekimab for Cardiovascular Protection in Chronic Kidney Disease (ISN-WCN 2025) - No abstract available

Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease • IL6

DESIGN OF THE ZEUS TRIAL: INTERLEUKIN 6 INHIBITION WITH ZILTIVEKIMAB FOR CARDIOVASCULAR PROTECTION IN CHRONIC KIDNEY DISEASE (ISN-WCN 2025) - P3 | "Although colchicine is effective at preventing CV events in patients with atherosclerotic CV disease (ASCVD), more targeted therapies are required, particularly for people with chronic kidney disease (CKD) who are at very high CV risk and for whom colchicine is contraindicated. Interim analyses for efficacy have been prespecified. Conclusions ZEUS will evaluate the effect of ziltivekimab on MACE and kidney outcomes in participants with CKD, ASCVD, and elevated hsCRP levels, as well as additional efficacy and safety endpoints, and is expected to be completed in 2026."

Late-breaking abstract • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Inflammation • Myocardial Infarction • Nephrology • Renal Disease • CRP • IL6

ATHENA: A Research Study Looking Into How Ziltivekimab Works Compared to Placebo in Participants With Heart Failure and Inflammation (clinicaltrials.gov) - P3 | N=680 | Recruiting | Sponsor: Novo Nordisk A/S | Trial completion date: Sep 2026 ➔ Jan 2027 | Trial primary completion date: Jun 2026 ➔ Oct 2026

Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure • Inflammation

"Anti-inflammatory Therapies in Atherosclerosis - Where are we going?". (PubMed, Curr Atheroscler Rep) - "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. 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."

Journal • Review • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Inflammation • Ischemic stroke • Myocardial Infarction • Nephrology • Renal Disease • CRP • IL6

What additional/alternative agents are in the pipeline (NsMRA, Ziltivekimab, ASI, Cagrisema, dual/triple Incretins, etc…)? (CVCT USA 2024) - No abstract available

Diabetes • Metabolic Disorders

Anti-inflammatory Agents and their Effect on Cardiovascular Disease: A Comprehensive Review of Literature (AHA 2024) - "Two RCT's evaluated immunomodulating agents, including the CANTOS trial which assessed canakinumab, an IL-1β inhibitor and the RESCUE trial which assessed ziltivekimab, an IL-6 inhibitor. The COLCOT and LoDoCo2 trials assessed colchicine while CIRT assessed methotrexate...The advancements in targeted immune therapies offer promising new avenues in cardiovascular medicine. Our systematic review of RCTs suggests that anti-inflammatory agents have a beneficial role in the reduction of cardiovascular events and the progression of CVD in patients with atherosclerotic disease. While the majority of the included RCTs support the use of these agents, the heterogeneity in the individual studies emphasize the need for further research to investigate the role of immunomodulating agents on CVD outcomes."

Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Inflammation • IL1B

ARTEMIS - A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With a Heart Attack (clinicaltrials.gov) - P3 | N=10000 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Myocardial Infarction

Effect of IL-6 Inhibition on Lipoprotein(a) Levels: A Systematic Review and Meta-Analysis (CMHC 2024) - "The analyses included ten studies with 1,201 total participants (876 rheumatoid arthritis, 325 chronic kidney disease) receiving either an anti-IL-6/IL-6R mAb (311 tocilizumab, 153 sarilumab, 247 ziltivekimab) or comparator (78 placebo, 412 TNFi). This meta-analysis indicates significant reductions in Lp(a) levels with anti-IL-6/IL-6R mAbs compared to controls. The potential clinical relevance for ASCVD prevention warrants further investigation in outcome trials"

Retrospective data • Review • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Immunology • Inflammatory Arthritis • Nephrology • Oncology • Renal Disease • Rheumatoid Arthritis • Rheumatology • IL6R

Ziltivekimab for anemia and atherosclerosis in chronic kidney disease: a new hope? (PubMed, J Nephrol) - "These trials have shown that ziltivekimab does not increase the risk for cytopenia or infectious complications as has been described for other interleukin-6-targeting monoclonal antibodies, like tocilizumab. In addition, ziltivekimab has shown efficacy in improving anemia parameters, including hemoglobin levels and iron studies. Ziltivekimab deserves full scale clinical development, and to this aim, large-scale clinical trials are under way."

Journal • Review • Anemia • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Dyslipidemia • Epilepsy • Hematological Disorders • Hypertension • Inflammation • Nephrology • Oncology • Renal Disease • Solid Tumor • IL6

Direct IL-6 inhibition prevents arterial thrombosis by reducing collagen-mediated platelets activation (ESC 2024) - "The recent phase 2 RESCUE trial reported that direct inhibition of IL-6 ligand by the monoclonal antibody (mAb) Ziltivekimab is safe in patients with elevated cardiovascular risk... The direct inhibition of IL-6 reduces platelets reactivity to collagen, thereby blunting arterial thrombosis upon endothelial damage. These results provide a potential mechanism to explain the reduction of cardiovascular risk associated to direct IL-6 inhibition."

Cardiovascular • Coronary Artery Disease • Thrombosis

Recent Advances in Targeted Management of Inflammation In Atherosclerosis: A Narrative Review. (PubMed, Cardiol Ther) - "Evidence suggests that high-sensitivity C-reactive protein (hsCRP), and potentially other inflammatory biomarkers, can be used to identify the inflammatory residual ASCVD risk phenotype and may serve as future targets for the development of more efficacious therapeutic approaches. We review the biological basis for the association of inflammation with ASCVD, propose new therapeutic strategies for the use of inflammation-targeted treatments, and discuss current challenges in the implementation of this new treatment paradigm for ASCVD."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Inflammation • CRP

ATHENA: A Research Study Looking Into How Ziltivekimab Works Compared to Placebo in Participants With Heart Failure and Inflammation (clinicaltrials.gov) - P3 | N=680 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Heart Failure • Inflammation

Impacts of pro-inflammatory cytokines variant on cardiometabolic profile and premature coronary artery disease: A systematic review and meta-analysis. (PubMed, J Cell Mol Med) - "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."

Journal • Retrospective data • Review • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Obesity

Status and Prospect of Anti-Inflammatory Therapeutic Pathway for Coronary Heart Disease (ISPOR 2024) - " Evidence from large CVOTs, including CANTOS, COLCOT, and LoDoCo2, suggests that anti-inflammatory drugs targeting the NLRP3 inflammasome/IL-1β pathway, such as Canakinumab and Colchicine, can effectively reduce the incidence of cardiovascular events...The RESCUE trial demonstrated that Ziltivekimab, a fully human monoclonal antibody targeting IL-6 ligand, significantly lowered biomarker levels of inflammation and thrombus formation in patients with moderate to severe chronic kidney disease with elevated hsCRP...conducted a multicenter trial that showed that hydroxychloroquine significantly reduced IL-6 levels, as compared with placebo, in patients with myocardial infarction (p < 0.05), but the impact on cardiovascular endpoints after myocardial infarction remains uncertain and requires a larger randomized clinical trial for verification... The NLRP3 inflammasome/IL-1β pathway is most likely to provide hope for the inclusion of anti-inflammatory therapy in the..."

Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Coronary Artery Disease • Dyslipidemia • Heart Failure • Inflammation • Myocardial Infarction • Nephrology • Renal Disease • Thrombosis • CRP • IL1B • IL6 • NLRP3

ZEUS - A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With Cardiovascular Disease, Chronic Kidney Disease and Inflammation (clinicaltrials.gov) - P3 | N=6200 | Recruiting | Sponsor: Novo Nordisk A/S | Trial completion date: Oct 2025 ➔ Jan 2026

Trial completion date • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Inflammation • Nephrology • Renal Disease • CRP

C-reactive protein, pharmacological treatments and diet: how to target your inflammatory burden. (PubMed, Curr Opin Lipidol) - "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."

Journal • Cardiovascular • Inflammation • CRP • IL6

A Research Study Looking Into Blood Levels of Three Different Formulations of the Study Medicine Ziltivekimab (clinicaltrials.gov) - P1 | N=267 | Completed | Sponsor: Novo Nordisk A/S | Active, not recruiting ➔ Completed

Trial completion

ATHENA: A Research Study Looking Into How Ziltivekimab Works Compared to Placebo in Participants With Heart Failure and Inflammation (clinicaltrials.gov) - P3 | N=680 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P3 trial • Cardiovascular • Congestive Heart Failure • Heart Failure • Inflammation

Effect of Ziltivekimab on Determinants of Hemoglobin in Patients with CKD Stage 3-5: An Analysis of a Randomized Trial (RESCUE). (PubMed, J Am Soc Nephrol) - P2b | "Anti-inflammatory therapy with ziltivekimab improved the markers of anemia and iron homeostasis in people with stage 3-5 CKD and systemic inflammation, suggesting a possible role in anemia management."

Journal • Chronic Kidney Disease • Hematological Disorders • Infectious Disease • Inflammation • Neutropenia • Novel Coronavirus Disease • Respiratory Diseases • Thrombocytopenia • CRP • IL6

An Update on Inflammation in Atherosclerosis: How to Effectively Treat Residual Risk. (PubMed, Clin Ther) - "Based on current evidence and ongoing clinical trials, targeting inflammation alongside optimal lipid lowering is likely to be central to the future treatment of ASCVD. (Clin Ther. 2023;45:XXX-XXX)"

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Hematological Disorders • Inflammation • Thrombosis • CRP • IL1B • IL6

A Research Study of How the Medicine Ziltivekimab Works in the Body of Chinese Men and Women With Kidney Disease and Inflammation (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Novo Nordisk A/S | Trial primary completion date: Jul 2023 ➔ May 2024

Trial primary completion date • Chronic Kidney Disease • Inflammation • Nephrology • Renal Disease • CRP