Novo Nordiskhas announced headline results from the cardiovascular outcomes from a phase 3 trial.
While ziltivekimab demonstrated target engagement and inhibition of the IL-6 pathway, as reflected by expected reductions in free IL-6 and high-sensitivity C-reactive protein (hsCRP) respectively, this did not translate into major adverse cardiovascular events (MACE) risk reduction versus placebo in people with atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD) and inflammation (hazard ratio, 0.99; 95% confidence interval, 0.88 to 1.11).
Zeus was a double-blind, placebo-controlled trial enrolling over 6,300 people with ASCVD, CKD, and inflammation, as measured by hsCRP levels ≥2 mg/L. The trial evaluated once-monthly ziltivekimab 15 mg versus placebo for reducing the risk of MACE, defined as cardiovascular (CV) death, non-fatal heart attack or non-fatal stroke.
Overall rates of adverse events and serious adverse events in people treated with ziltivekimab were similar to those observed with placebo. Consistent with targeting IL-6 inhibition, a higher proportion of people treated with ziltivekimab had serious infections compared to placebo. No difference in all-cause mortality was observed.
The two additional ongoing cardiovascular outcomes trials investigating ziltivekimab in people with heart failure and in people following an acute heart attack are planned to continue and are anticipated to read out in the first half of 2027.
