Novo Nordisk’s IL-6 inhibitor ziltivekimab has failed to meet its primary cardiovascular endpoint in the phase 3 ZEUS trial, dashing expectations that lowering inflammation would translate into fewer major adverse cardiovascular events. In a late-stage study across atherosclerotic cardiovascular disease, chronic kidney disease, and inflammation populations, ziltivekimab did not reduce the risk of cardiovascular events such as heart attack, stroke, or cardiovascular death compared with control. Novo’s shares fell nearly 9% on the news. Novo said the program’s scientific findings will inform ongoing cardiovascular research, while the asset continues to be evaluated in other studies including HERMES in heart failure and ARTEMIS in acute heart attack. The result raises pressure to show differentiating clinical benefit in a crowded cardiometabolic field while also testing the translational value of IL-6 pathway intervention for hard clinical outcomes.