MANY MINDEDThe inflammation bet in heart disease returns a null result
Novo Nordisk announced headline results from the ZEUS phase 3 trial on 31 July 2026: ziltivekimab did not reduce major adverse cardiovascular events compared with placebo, missing the trial's primary endpoint.
ZEUS was a double-blind, placebo-controlled trial in more than 6,300 people with atherosclerotic cardiovascular disease, chronic kidney disease and elevated inflammation, testing once-monthly ziltivekimab at 15 mg. The primary endpoint combined cardiovascular death, non-fatal heart attack and non-fatal stroke. The hazard ratio was 0.99, with a 95% confidence interval of 0.88 to 1.11 — an interval centred on no effect. The drug did what it was designed to do biologically: it engaged the interleukin-6 pathway, and free IL-6 and high-sensitivity C-reactive protein fell as expected. That engagement did not translate into fewer cardiovascular events. Serious infections were more common on the drug than on placebo.
This is a setback with unusual informational value. A large body of work has proposed that inflammation is a modifiable driver of cardiovascular risk, and ziltivekimab was among the most direct tests of it — a well-powered trial in exactly the population where the hypothesis should have been strongest. A null result at this size and precision constrains the hypothesis rather than leaving it open, and that is worth something, even though it costs a candidate therapy aimed at the leading cause of death worldwide.
Two trials continue. HERMES, in heart failure, and ARTEMIS, in patients recovering from an acute heart attack, are both proceeding as planned and are expected to report in the first half of 2027. Those populations differ from the ZEUS group, so the programme is not finished — but the headline hypothesis has taken its clearest test and did not pass.
These are topline results announced by the sponsor; the full trial data has not yet been published or peer-reviewed.
Source: Fierce Biotech