Novo Nordisk's ziltivekimab fails to reduce heart risk in ZEUS trial
Novo Nordisk (NYSE: NVO) announced that its experimental drug ziltivekimab did not reduce the risk of major adverse cardiovascular events (MACE) in a phase 3 clinical trial, despite producing the expected biological effects.
The ZEUS trial, a double-blind, placebo-controlled study enrolling over 6,300 patients with atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and elevated inflammation markers, compared once-monthly ziltivekimab 15 mg against placebo. The primary endpoint was a reduction in MACE, defined as cardiovascular death, non-fatal heart attack, or non-fatal stroke. The hazard ratio was 0.99 with a 95% confidence interval of 0.88 to 1.11, indicating no meaningful benefit over placebo.
Ziltivekimab did produce reductions in free IL-6 and high-sensitivity C-reactive protein (hsCRP), confirming target engagement, but these biological effects did not translate into fewer 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 and chief scientific officer at Novo Nordisk.
Rates of adverse events and serious adverse events were similar between the ziltivekimab and placebo groups overall, though a higher proportion of patients treated with ziltivekimab experienced serious infections. No difference in all-cause mortality was observed.
Novo Nordisk said the ZEUS outcome will not affect its previously communicated adjusted operating profit outlook for 2026 but will result in a non-cash impairment charge in the third quarter of 2026.
Two additional cardiovascular outcomes trials evaluating ziltivekimab — HERMES in heart failure patients and ARTEMIS in patients following an acute heart attack — are set to continue, with results expected in the first half of 2027.
Full results from the ZEUS trial are expected to be presented at a scientific meeting later in 2026.