Ziltivekimab Significantly Reduces Multiple Inflammatory Biomarkers in High-Risk Atherosclerotic CKD Patients, Phase 2 RESCUE Trial Shows

May 18, 2021 /BIOONBIOON/ -- Novo Nordisk recently announced the results of the Phase 2 RESCUE study. This is a randomized, double-blind, placebo-controlledClinical Trial, conducted in patients with advanced chronic kidney disease (CKD) and elevated high-sensitivity C-reactive protein (hsCRP), evaluated the effect of once-monthly subcutaneous administration of the interleukin-6 (IL-6) inhibitor ziltivekimab on inflammatory biomarkers. The trial demonstrated that, compared with placebo,Ziltivekimab treatment reduces multiple atherosclerosis-related inflammatory pathwaysBiomarkerLevels were significantly reduced, including hsCRP.

These data at the recently held 70th Annual Scientific Session of the American College of CardiologyConferencepresented at (ACC.21) and simultaneously published in the international medical journal *The Lancet*, titled:IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial。

Chronic Kidney Disease and Cardiovascular Disease (Image source: sunlightpharmacy.com)

Cardiovascular disease (CVD) is the leading cause of global morbidity and mortality, accounting for one-third of all deaths worldwide, 85% of which are caused by heart attacks and strokes. Furthermore, approximately half of all deaths among patients with chronic kidney disease (CKD) are due to CVD-related complications, meaning that CKD patients are more likely to die from CVD than to progress to end-stage renal disease.

Atherosclerosis is the primary cause of cardiovascular disease (CVD), including heart attack and stroke. Atherosclerosis is characterized by the accumulation of fats, cholesterol, and other substances in the form of plaques on the arterial walls, leading to arterial narrowing and reduced blood flow. Chronic inflammation promotes the formation and progression of atherosclerosis. Elevated hsCRP levels are a marker of inflammationBiomarker, can be used to predict the risk of cardiovascular events, such as heart attack and stroke. Elevated hsCRP indicates a high risk of cardiovascular disease. Chronic inflammation is common in patients with chronic kidney disease (CKD), placing them at an increased risk of cardiovascular events such as heart attack and stroke.

Pro-inflammatory cytokine IL-6 (Click the image to view a larger version)

Globally, 700 million people are affected by CKD, and this number continues to rise. Kidney damage is associated with chronic inflammation, which is considered a key driver of atherosclerotic cardiovascular disease (ASCVD). Despite adherence to guideline-recommended management of cardiovascular risk factors, the high risk of cardiovascular events in patients with CKD persists.

ziltivekimab is a fully human monoclonal antibody designed to reduce systemic inflammation by inhibiting IL-6, a pro-inflammatory cytokine that plays a causal role in atherosclerosis. Utilizing half-life extension technology, ziltivekimab is designed for once-monthly subcutaneous administration. Following the announced acquisition of Corvidia Therapeutics in June 2020, ziltivekimab is being developed by Novo Nordisk,This drug has the potential to become the first therapy to reduce the risk of major adverse cardiovascular events in CKD patients with ASCVD and inflammation.

RESCUE is a randomized, double-blind, placebo-controlled Phase 2Clinical Trial, is evaluating the effect of once-monthly subcutaneous ziltivekimab on inflammatory biomarkers in patients with advanced CKD and elevated hsCRP. This study enrolled a total of 264 patients and aims to assess whether ziltivekimab can safely and effectively reduce the levels of inflammatory biomarkers associated with atherosclerosis. The pre-specified primary endpoint is the change in hsCRP at 12 weeks of treatment, along with safety and other inflammatory`Biomarker`Additional data on (fibrinogen, serum amyloid A, haptoglobin, and secretory phospholipase A2).

hsCRP data

Data presented at this meeting showed that the RESCUE study met its primary endpoint: after 12 weeks of treatment, compared with the placebo group,Median hs-CRP levels were significantly reduced in patients in the ziltivekimab treatment group.(Patients receiving 7.5 mg, 15 mg, and 30 mg ziltivekimab showed reductions of 77%, 88%, and 92%, respectively, compared with 4% in the placebo group). Regarding secondary endpoints, the proportions of patients achieving a >50% reduction in hsCRP levels and those with hsCRP levels <2 mg/L were also significantly higher in the ziltivekimab treatment groups than in the placebo group (66%, 80%, and 93% in the 7.5 mg, 15 mg, and 30 mg ziltivekimab groups, respectively, versus 4% in the placebo group).

Furthermore,4 Additional Types of InflammationBiomarker(Fibrinogen, serum amyloid A, haptoglobin, and secretory phospholipase A2) also decreased in a dose-dependent manner.In this study, adverse events were similar between the placebo group and the ziltivekimab treatment group. Ziltivekimab was generally well-tolerated, with no unexpected adverse effects.

Martin Holst Lange, Executive Vice President of Development at Novo Nordisk, stated: “We are highly encouraged by these promising Phase 2 data, which mark an important step toward bringing a novel potential anti-inflammatory therapy to patients with atherosclerotic CVD and CKD. Based on these results, we are planning to advance ziltivekimab into a large-scale Phase 3 cardiovascular outcomes trial to further evaluate its potential, while continuing to advance our commitment to cardiovascular disease.” (Bioon.com)

Original Source: Ziltivekimab reduced inflammatory biomarkers associated with atherosclerosis in people with chronic kidney disease in phase 2 trial