Novo Nordisk Ziltivekimab ZEUS Phase 3 Fails to Reduce Cardiovascular Events in ASCVD Plus CKD Population; Shares Fall More Than 9%
Novo Nordisk (NYSE: NVO) announced at ESC Congress 2026 that its Phase 3 ZEUS trial of ziltivekimab (an anti-IL-6 monoclonal antibody in development for cardiovascular risk reduction in inflammation-driven disease) failed to reduce major adverse cardiovascular events (MACE) versus placebo in patients with atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and inflammation (hsCRP ≥2 mg/L). The three-component MACE primary endpoint hazard ratio was 0.99 (95% CI 0.88-1.11), despite confirmed IL-6 pathway engagement (reductions in free IL-6 and hsCRP as expected). Safety was broadly similar between arms though serious infections were more frequent on ziltivekimab (consistent with the IL-6 class). NVO shares fell more than 9% on the readout, deepening the widening H1 2026 GLP-1 revenue gap that already sat at $10.2 billion versus Eli Lilly. Novo has committed to continuing the two other cardiovascular outcomes trials (HERMES in heart failure, ARTEMIS post-acute MI) with H1 2027 readouts. The ZEUS miss casts doubt on the broader thesis of anti-inflammatory cardiovascular risk reduction via IL-6 blockade.