Novo Nordisk's ziltivekimab failed to reduce major adverse cardiovascular events in the Phase III ZEUS trial, sending US-listed shares down more than 10 percent in pre-market trading. The drug showed a hazard ratio of 0.99 versus placebo despite demonstrating expected biological effects on inflammation markers.
Novo Nordisk's ziltivekimab failed to cut cardiovascular events in a Phase III trial, sending US-listed shares down more than 10 percent in pre-market trading.
"While ziltivekimab produced the expected biological effect, this did not result in MACE benefits in this population," Martin Holst Lange, executive vice president and chief scientific officer at Novo Nordisk, said.
The ZEUS trial enrolled over 6,300 people with atherosclerotic cardiovascular disease, chronic kidney disease, and inflammation, testing once-monthly ziltivekimab 15 mg against placebo. The drug showed a hazard ratio of 0.99 (95 percent confidence interval 0.88 to 1.11) for major adverse cardiovascular events, defined as cardiovascular death, non-fatal heart attack, or non-fatal stroke. Serious infections were more common with ziltivekimab, consistent with IL-6 pathway inhibition, while all-cause mortality showed no difference between groups.
The failure is the latest setback for the Danish drugmaker as it works to restore investor confidence in its pipeline and execution, particularly in the US market. Copenhagen-listed shares fell 7.4 percent, according to the Wall Street Journal. The company will record a non-cash impairment charge in Q3 2026, and two additional ziltivekimab trials — HERMES in heart failure and ARTEMIS following acute heart attack — are expected to read out in the first half of 2027.
The trial was designed to test whether inhibiting the IL-6 pathway could translate reductions in cardiovascular inflammation into fewer major cardiovascular events. Ziltivekimab demonstrated target engagement with expected reductions in free IL-6 and high-sensitivity C-reactive protein, but these biological effects did not translate into clinical benefit.
Overall adverse event rates were similar between treatment groups, though a higher proportion of ziltivekimab-treated patients experienced serious infections. The company said the outcome will not affect its previously communicated adjusted operating profit outlook for 2026.
The ZEUS failure adds to pressure on Novo Nordisk, whose shares had already fallen 7 percent year-to-date before Friday's announcement. The company has been racing to diversify beyond its GLP-1 franchise — including Wegovy and Ozempic — as competition intensifies from Eli Lilly and other weight-loss drug developers.
Full results of the ZEUS trial will be presented at an upcoming scientific meeting in 2026. The outcome raises questions about the broader IL-6 inhibition approach in cardiovascular disease, though the ongoing HERMES and ARTEMIS trials will provide additional data on ziltivekimab's potential in heart failure and post-heart-attack settings.
The ZEUS failure removes a key pipeline milestone for Novo Nordisk's cardiovascular ambitions, leaving investors to focus on the HERMES and ARTEMIS readouts in the first half of 2027. The company's ability to defend its GLP-1 franchise against Eli Lilly will remain the primary driver of its shares.
This article is for informational purposes only and does not constitute investment advice.
