Novo Nordisk’s monoclonal antibody (mAb) designed to reduce the risk of major adverse cardiovascular events (MACE) in patients with atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD) and inflammation has failed to meet the primary endpoint in a Phase III trial.
The ZEUS study (NCT05021835) enrolled 6,385 patients with high-sensitivity C-reactive protein (hsCRP) levels measured at ≥2 mg/L. Patients were randomised to receive either once-monthly ziltivekimab 15mg or placebo for reducing the risk of MACE, defined as cardiovascular (CV) death, non-fatal heart attack or non-fatal stroke.
Go deeper with GlobalData
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
Novo said that while ziltivekimab demonstrated target engagement and inhibition of the IL-6 pathway, as reflected by expected reductions in free IL-6 and hsCRP, respectively, this did not translate into MACE reduction.
Martin Holst Lange, executive VP, CSO and head of R&D at Novo Nordisk, said: “While ziltivekimab did not achieve the MACE benefit we had hoped for, this does not change our strategic commitment to cardiovascular disease. The study provides important scientific evidence that will inform our ongoing cardiovascular research and the development of treatments for patients who continue to face substantial unmet need.”
The obesity and type 2 diabetes drug giant added that overall rates of adverse events (AEs) and serious AEs in people treated with ziltivekimab were similar to those observed with placebo. Consistent with targeting IL-6 inhibition, a higher proportion of people treated with ziltivekimab had serious infections compared to placebo.
There are two additional ongoing cardiovascular outcomes trials investigating ziltivekimab in people with heart failure (NCT05636176) and in people who have had an acute heart attack (NCT06118281) that are planned to continue and are anticipated to read out in the first half of 2027.
The company added that while the outcome of ZEUS will not impact Novo Nordisk’s adjusted operating profit outlook for 2026, it will result in a non-cash impairment charge in Q3 2026.
Full results of the ZEUS trial will be presented at an upcoming scientific meeting in 2026.
In the Phase II RESCUE trial, ziltivekimab substantially lowered various inflammatory biomarkers linked to atherosclerosis in advanced CKD patients. Data showed that the trial met its primary endpoint, with the median hsCRP levels substantially lowered in those receiving the treatment as against placebo after 12 weeks.
