Novo Nordisk shares headline results from the ZEUS Phase 3 trial in people with ASCVD, CKD, and inflammation

Although ziltivekimab achieved the expected biological effects, including reductions in free IL-6 and high-sensitivity C-reactive protein consistent with IL-6 pathway inhibition and target engagement, these changes did not translate into a reduction in major adverse cardiovascular events against placebo in people living with atherosclerotic cardiovascular disease, chronic kidney disease, and elevated inflammatory markers.

ZEUS was a double-blind, placebo-controlled trial recruiting more than 6,300 people with atherosclerotic cardiovascular disease, chronic kidney disease, and inflammation as measured by high-sensitivity C-reactive protein levels of 2 mg/L or above. The trial examined once-monthly ziltivekimab at 15 mg versus placebo for its ability to reduce the risk of major adverse cardiovascular events, defined as cardiovascular death, non-fatal heart attack, or non-fatal stroke.

“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,” said Martin Holst Lange, Executive Vice President, Chief Scientific Officer and Head of Research and Development, Novo Nordisk. “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.”

Rates of adverse events and serious adverse events among those receiving ziltivekimab were comparable to those seen with placebo throughout the trial. In keeping with the mechanism of IL-6 inhibition, a greater proportion of participants on ziltivekimab experienced serious infections relative to those on placebo. No difference in all-cause mortality was recorded between the two groups.

The two further cardiovascular outcomes trials examining ziltivekimab, one in people with heart failure through the HERMES study and another in people recovering from an acute heart attack through the ARTEMIS study, are both continuing as planned, with results anticipated in the first half of 2027.

The ZEUS outcome will have no bearing on Novo Nordisk’s previously communicated adjusted operating profit guidance for 2026, though a non-cash impairment charge will be recognised in the third quarter of 2026.

---

---

Related Topics and Keywords

ASCVD, ckd, Novo Nordisk, ZEUS Phase 3 trial