Novo Nordisk ZEUS trial misses MACE endpoint

Novo Nordisk announced headline results from the ZEUS phase 3 cardiovascular outcomes trial, which evaluated ziltivekimab, an investigational IL-6 ligand inhibitor, in over 6,300 patients with atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and inflammation. The trial failed to show a reduction in major adverse cardiovascular events (MACE) versus placebo, with a hazard ratio of 0.99 (95% CI 0.88-1.11). Although ziltivekimab demonstrated expected reductions in free IL-6 and high-sensitivity C-reactive protein, this did not translate into clinical benefit. Safety was generally consistent with placebo, though serious infections were more common with ziltivekimab. The outcome will not affect Novo Nordisk's 2026 adjusted operating profit outlook but will result in a non-cash impairment charge in Q3 2026. Two other trials, HERMES and ARTEMIS, are continuing and expected to read out in the first half of 2027.