Novo Nordisk said its Phase 3 ZEUS cardiovascular outcomes trial failed to show a reduction in major adverse cardiovascular events with ziltivekimab, an IL-6 inhibitor. The update landed after the company reported the drug inhibited the IL-6 pathway and lowered high-sensitivity C-reactive protein, but the mechanism did not translate into improved clinical outcomes versus placebo. The study enrolled more than 6,300 patients with atherosclerotic cardiovascular disease, chronic kidney disease, and inflammation. Novo reported a hazard ratio of 0.99 (95% CI, 0.88-1.11) for the primary endpoint, underscoring the gap between biomarker suppression and event reduction. The disappointment adds pressure to Novo’s inflammatory heart disease strategy and raises uncertainty about how quickly similar cytokine-targeted programs could prove clinical benefit in comparable high-risk populations. Novo indicated it has ongoing studies (Artemis and Hermes) that may inform next steps for the CKD-linked inflammation franchise.