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Novo Nordisk says phase 3 ZEUS trial misses cardiovascular endpoint

Novo Nordisk says phase 3 ZEUS trial misses cardiovascular endpoint

Shares fell about 9.5% to 10%, erasing about $30.7 billion in market value, after ziltivekimab failed to reduce major adverse cardiovascular events versus placebo; 2026 adjusted operating profit guidance is unchanged.

Fact Check
Novo Nordisk's own press release (GlobeNewswire) confirms ziltivekimab failed to reduce MACE versus placebo in the ZEUS phase 3 trial, missing the primary cardiovascular endpoint. CNBC independently confirms shares fell as much as 10% on the news, consistent with the claimed ~9.5-10% drop. The guidance-unchanged element is plausible given the company only flagged a non-cash impairment charge. Multiple authoritative primary sources support the claim.
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Summary

Novo Nordisk said its phase 3 ZEUS cardiovascular outcomes trial failed to show that ziltivekimab reduced major adverse cardiovascular events in people with atherosclerotic cardiovascular disease, chronic kidney disease and inflammation, reporting a hazard ratio of 0.99 with a 95% confidence interval of 0.88 to 1.11. The investigational monoclonal antibody showed target engagement and IL-6 pathway inhibition, including reductions in free IL-6 and high-sensitivity C-reactive protein, but that did not translate into lower MACE risk versus placebo. Novo Nordisk shares fell sharply, by as much as 10% and around 9.5% in European afternoon trading, wiping out about $30.7 billion in market value and reducing the company’s market capitalization to about $198.5 billion from $229.2 billion. The company said safety was broadly similar to placebo overall, though serious infections were more frequent with ziltivekimab, all-cause mortality showed no difference, 2026 adjusted operating profit guidance is unchanged, and a non-cash impairment charge will be recorded in the third quarter. HERMES and ARTEMIS, two other ziltivekimab cardiovascular outcomes trials, are continuing and are expected to report in the first half of 2027.

Terms & Concepts
  • MACE: Major adverse cardiovascular events such as cardiovascular death, non-fatal heart attack or non-fatal stroke.
  • IL-6 pathway: Inflammation signaling route involving interleukin-6.
  • hsCRP: High-sensitivity C-reactive protein, a blood marker used to measure inflammation.