Novo Nordisk has reported that the Phase III ZEUS trial of ziltivekimab, an IL-6 monoclonal antibody (mAb) acquired via Corvidia Therapeutics, did not meet its primary endpoint of reducing three-point major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) in patients with atherosclerotic cardiovascular disease, chronic kidney disease (CKD), and systemic inflammation.

The study enrolled over 6,300 participants receiving 15 mg subcutaneous monthly dosing versus placebo. Although ziltivekimab lowered free IL-6 and high-sensitivity C-reactive protein, the MACE hazard ratio was 0.99. Infection-related serious adverse events (SAEs) were numerically higher in the active arm, consistent with IL-6 pathway suppression.

Two additional Phase III cardiovascular outcome trials – HERMES in heart failure and ARTEMIS in acute myocardial infarction – remain ongoing, with readouts expected in the first half of 2027. The ZEUS miss tempers enthusiasm for IL-6 inhibition as a broad cardiorenal protective strategy, contrasting with the validated success of IL-1 and SGLT2 mechanisms in similar populations, and narrows Novo's inflammation-based cardiovascular ambitions to the remaining datasets before any repositioning decision.