Detailed findings from the ZEUS clinical trial, presented in Chicago on Saturday, November 7, showed that the experimental anti-inflammatory drug ziltivekimab did not significantly reduce major cardiovascular events in the population studied, according to Mass General Brigham.
The institution said the combined outcome of heart attack, stroke or cardiovascular death occurred in 561 participants receiving the drug and 565 receiving placebo. The findings were presented at the American Heart Association’s Scientific Sessions and published alongside the presentation.
ZEUS tested a monthly 15-milligram injection against placebo on top of standard care. The phase 3 study enrolled more than 6,300 people with atherosclerotic cardiovascular disease, chronic kidney disease and elevated inflammation, according to sponsor Novo Nordisk.
Ziltivekimab targets interleukin-6, an inflammatory molecule. It produced the intended biological changes, but those changes did not translate into a statistically significant reduction in the trial’s main cardiovascular outcome.
The neutral headline result was announced July 31. Saturday’s detailed presentation and publication add to that earlier disclosure; the lack of benefit was not first announced today. The sponsor’s July report put the hazard ratio at 0.99, with a 95% confidence interval of 0.88 to 1.11.
Mass General Brigham said no difference in total mortality was observed, while infections were more frequent in the treatment group. The institution identified Novo Nordisk as the study’s funder.
Lead investigator Paul Ridker and colleagues said the participants’ advanced illness and the particular inflammatory target were possible explanations requiring further research. The findings concern this drug and this trial population; they do not establish that every approach to targeting cardiovascular inflammation is ineffective.
Sources: Mass General Brigham — November 7 detailed ZEUS findings. Novo Nordisk — July 31 headline-results announcement, background. American Heart Association — November 7 late-breaking science program.