Novo Nordisk took another hit as its Phase 3 cardiovascular outcomes program for ziltivekimab failed to reduce major adverse cardiovascular events versus placebo. The Zeus trial enrolled more than 6,300 patients with atherosclerotic cardiovascular disease, chronic kidney disease, and inflammation; despite IL-6 pathway inhibition and CRP reduction, the benefit did not translate into the primary endpoint. Novo said the hazard ratio for MACE risk reduction was 0.99 (95% CI 0.88–1.11), prompting renewed scrutiny of inflammatory-heart-disease strategies that target the IL-6 axis. Shares fell sharply after the update. Novo’s management flagged ongoing “Artemis” and “Hermes” trials as potential salvage routes for the broader inflammation CKD portfolio, but Zeus adds fresh uncertainty to the clinical viability of this mechanism in cardiovascular risk reduction.