Novo Nordisk has announced headline results from the ZEUS cardiovascular outcomes phase 3 trial.

While ziltivekimab demonstrated target engagement and inhibition of the IL-6 pathway, as reflected by expected reductions in free IL-6 and high-sensitivity C-reactive protein (hsCRP) respectively, this did not translate into Major Adverse Cardiovascular Events (MACE) risk reduction versus placebo in people with atherosclerotic cardiovascular disease (ASCVD), Chronic Kidney Disease (CKD) and inflammation (hazard ratio, 0.99; 95 percent Confidence Interval (CI), 0.88 to 1.11).

ZEUS was a double-blind, placebo-controlled trial enrolling more than 6,300 people with ASCVD, CKD, and inflammation, as measured by hsCRP levels ≥2 mg/L. The trial evaluated once-monthly ziltivekimab 15 mg versus placebo for reducing the risk of MACE, defined as cardiovascular (CV) death, non-fatal heart attack or non-fatal stroke.

Martin Holst Lange, Executive Vice President (EVP), Chief Scientific Officer (CSO) and Head of Research and Development (R&D), Novo Nordisk, said, “ZEUS was designed to test whether inhibition of the IL-6 pathway could translate reductions in cardiovascular inflammation into fewer major cardiovascular events. Although ziltivekimab produced the expected biological effect, this did not result in MACE benefits in this population. 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.”

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. No difference in all-cause mortality was observed.

The 2 additional ongoing cardiovascular outcomes trials investigating ziltivekimab in people with heart failure (HERMES) and in people following an acute heart attack (ARTEMIS) are planned to continue and are anticipated to read out in the first half of 2027.

The outcome of ZEUS will not impact Novo Nordisk’s previously communicated adjusted operating profit outlook for 2026 but 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.