NVO stock was hit after Novo Nordisk said ziltivekimab missed its cardiovascular goal in the ZEUS cardiovascular outcomes phase 3 trial. The drug posted a hazard ratio of 0.99 for major adverse cardiovascular events, with a 95% confidence interval of 0.88 to 1.11. That left investors with a clean read: the biological signal was there, but the event data were not.
Martin Holst Lange on ZEUS
31 July 2026 brought the headline from Bagsværd, Denmark, where Novo Nordisk disclosed that ZEUS did not reduce MACE versus placebo in people with ASCVD, CKD, and inflammation. Martin Holst Lange said, “ZEUS was designed to test whether inhibition of the IL-6 pathway could translate reductions in cardiovascular inflammation into fewer major cardiovascular events.”
Over 6,300 people were enrolled, all with hsCRP levels of at least 2 mg/L, and the trial used once-monthly ziltivekimab 15 mg against placebo. The endpoint tracked cardiovascular death, non-fatal heart attack, and non-fatal stroke, so the 0.99 hazard ratio means the treatment arm was essentially flat against placebo on the study’s core measure.
IL-6 pathway, no MACE gain
Ziltivekimab did what it was built to do on biology: it showed target engagement and inhibition of the IL-6 pathway. Martin Holst Lange put the split plainly: “Although ziltivekimab produced the expected biological effect, this did not result in MACE benefits in this population.”
The result also came with a mixed safety readout. Overall adverse events and serious adverse events were similar in the two groups, but a higher proportion of people treated with ziltivekimab had serious infections than those on placebo. No difference in all-cause mortality was observed.
Q3 2026 charge, 2027 readouts
The commercial hit is limited for 2026 profit guidance, because Novo Nordisk said the ZEUS outcome will not affect its previously communicated adjusted operating profit outlook for the year. The accounting hit will still show up: the company said the result will lead to a non-cash impairment charge in Q3 2026.
HERMES and ARTEMIS are planned to continue, and both are anticipated to read out in the first half of 2027. Full ZEUS results will be presented at an upcoming scientific meeting in 2026, leaving the central scientific question in view: why IL-6 pathway inhibition did not convert into fewer cardiovascular events in this population.
