Novo Nordisk today presented results from RESCUE, a phase 2 randomized, double-blind, placebo-controlled clinical trial assessing the effect of once-monthly, investigational ziltivekimab, an interleukin-6 (IL-6) inhibitor, on biomarkers of inflammation. The trial showed a significant reduction of multiple inflammatory biomarkers associated with atherosclerosis in people with advanced chronic kidney disease (CKD) and elevated high-sensitivity C-reactive protein (hsCRP), representing high cardiovascular risk. The data were announced today at the virtual American College of Cardiology's (ACC) 70th Annual Scientific Session1 and simultaneously published in The Lancet2.
Atherosclerosis is the major cause of cardiovascular disease (CVD), including heart attack and stroke3. Atherosclerosis is characterized by the build-up of fats, cholesterol, and other substances in the artery walls that results in vessel narrowing and reduced blood flow3. Chronic inflammation contributes to the development and progression of atherosclerosis4, and biomarkers for inflammation, such as hsCRP, can be used to predict cardiovascular risk5.
The RESCUE trial met its primary endpoint, showing that after 12 weeks, median levels of hsCRP were significantly reduced with ziltivekimab compared with placebo (77%, 88%, and 92% reduction in those receiving 7.5 mg, 15 mg, and 30 mg of ziltivekimab, respectively, compared to 4% for placebo). The proportion of people achieving both a greater than 50% reduction in hsCRP and hsCRP levels of less than 2 mg/L, a secondary endpoint, was also significantly higher with ziltivekimab than placebo (66%, 80%, and 93% in those receiving 7.5 mg, 15 mg and 30 mg of ziltivekimab, respectively, compared to 4% for placebo). Dose-dependent reductions were also observed for four additional inflammatory biomarkers (fibrinogen, serum amyloid A, haptoglobin, and secretory phospholipase A2). Treatment emergent adverse events were considered to be mild, moderate, or severe and were similar between the placebo and ziltivekimab groups. Ziltivekimab was generally well tolerated, with no unexpected side effects2.
"In the RESCUE trial, ziltivekimab showed significant reductions in inflammatory biomarkers associated with atherosclerosis, including hsCRP," said Paul M. Ridker, director of the Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, US. "Chronic inflammation is common in people with chronic kidney disease and puts them at increased risk of cardiovascular events, such as heart attack and stroke."
CVD is the number one cause of morbidity and mortality globally6. It is responsible for one-third of all deaths worldwide, 85% of which are caused by heart attack and stroke3. Furthermore, approximately half of all deaths in people with CKD are due to CVD-related complications7, meaning those with CKD are more likely to die from CVD than progress to end-stage renal disease8.
"We are very encouraged by these promising phase 2 data, which is an important step towards a new potential anti-inflammatory treatment approach for people living with atherosclerotic CVD and CKD," said Martin Holst Lange, executive vice president for Development at Novo Nordisk. "Based on these results, we are planning to progress ziltivekimab to a large-scale phase 3 cardiovascular outcomes trial to further assess its potential, as we continue to advance our commitment in cardiovascular disease."