Novo Nordisk's ziltivekimab fails ZEUS heart trial, erasing $30 billion in market value

Novo Nordisk said on July 31 that ziltivekimab, an experimental anti-inflammatory antibody, failed to reduce heart attacks, strokes and cardiovascular deaths in a large phase 3 trial. The company's shares fell sharply the same day, erasing more than $30 billion in market value ^[1][2].

ZEUS enrolled more than 6,300 people with atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD) and inflammation, measured as high-sensitivity C-reactive protein (hsCRP) of at least 2 mg/L ^[1]. Participants in the double-blind, placebo-controlled trial received once-monthly injections of ziltivekimab 15 mg or a placebo on top of standard care ^[1]. The main endpoint was the combined risk of cardiovascular death, non-fatal heart attack or non-fatal stroke ^[1].

The hazard ratio was 0.99, with a 95% confidence interval of 0.88 to 1.11 ^[1][3]. A hazard ratio of 1.00 means no difference between the drug and placebo. Ziltivekimab did produce the biological effects Novo Nordisk expected, lowering free IL-6 and hsCRP, but the company said that did not translate into fewer cardiovascular events ^[1]. The size of the hsCRP reduction was not disclosed ^[2]. Full results will be presented at an upcoming scientific meeting in 2026 ^[1][3].

"ZEUS was designed to test whether inhibition of the IL-6 pathway could translate reductions in cardiovascular inflammation into fewer major cardiovascular events," said Martin Holst Lange, Novo Nordisk's executive vice president and chief scientific officer. "Although ziltivekimab produced the expected biological effect, this did not result in MACE benefits in this population" ^[1].

Overall rates of adverse events and serious adverse events were similar to those seen with placebo, and there was no difference in all-cause mortality ^[1]. A higher proportion of people taking ziltivekimab had serious infections, which the company said was consistent with blocking the IL-6 pathway ^[1][3].

Shares fell 9.3% to about $46.70 by Friday morning, the stock's largest intraday loss since February and a 10.6% decline for the year ^[2]. Market value dropped from $229.2 billion to $198.5 billion, a loss of $30.7 billion, and is down nearly 69% from an all-time high of $635.7 billion in June 2024 ^[2]. Jefferies analysts wrote that the drug would have needed to show at least a 20% reduction in risk and called the result "strategically negative," saying it erased a growth opportunity that could have been worth more than $10 billion a year ^[2]. Goldman Sachs analysts had praised the drug's potential before the results ^[2].

Novo Nordisk said the outcome will not change its adjusted operating profit outlook for 2026 but will result in a non-cash impairment charge in the third quarter of 2026 ^[1].

Why it matters for patients

Ziltivekimab is not approved for any use. It is an investigational monoclonal antibody being developed for cardiovascular disease, acute heart attack and heart failure with preserved ejection fraction ^[1]. The failure does not remove a treatment that patients currently have. Novo Nordisk is the maker of Ozempic and Wegovy ^[2], but ziltivekimab is a separate experimental product and not a GLP-1 drug ^[1].

For the group studied in ZEUS — people with ASCVD, CKD and elevated hsCRP — the trial leaves no new inflammation-targeting option from this program. Whether the result weakens the broader idea that treating inflammation prevents cardiovascular events is now under debate. TCTMD reported that cardiologists took to social media to discuss whether the outcome ends the inflammatory hypothesis. One physician wrote that a neutral result should not be read as disproving the link between hsCRP and cardiovascular events, while noting that a hazard ratio of 0.99 despite clear target engagement "should prompt" further discussion ^[3].

Other anti-inflammatory approaches remain in use. The FDA approved colchicine in 2023 as the first anti-inflammatory drug to prevent cardiovascular events in people with established ASCVD, based on the LoDoCo2 trial, and a 2019 US primary prevention guideline lists persistently elevated inflammatory markers as a risk-enhancing factor ^[3]. An American College of Cardiology scientific statement published before the ZEUS results said clinicians should take inflammation into account in cardiovascular risk, while acknowledging uncertainties ^[3].

What happens next

Two other ziltivekimab trials are continuing: HERMES, in people with heart failure, and ARTEMIS, in people who have had an acute heart attack. Both are expected to report results in the first half of 2027 ^[1][3]. Full ZEUS results will be presented at a scientific meeting in 2026; a date has not been announced ^[1][3]. Novo Nordisk expects to record the impairment charge in the third quarter of 2026 ^[1].