Novo Nordisk halts two more ziltivekimab heart failure trials after futility finding

Novo Nordisk has ended two more late-stage trials of ziltivekimab, an experimental heart drug, after an independent data monitoring committee recommended stopping them. The company told investigators on September 4 that the HERMES and ATHENA trials would close early, and the decision became public on September 7 ^[1]. The thousands of heart failure patients enrolled in the two studies will stop receiving the monthly injection they signed up for, according to the company's notice to investigators ^[1]. Exact enrollment numbers for HERMES and ATHENA have not been reported.

The halt came about five weeks after Novo Nordisk said a separate ziltivekimab trial, ZEUS, had missed its main goal. ZEUS enrolled more than 6,300 people with atherosclerotic cardiovascular disease, chronic kidney disease and inflammation, defined as a high-sensitivity C-reactive protein (hsCRP) level of 2 mg/L or higher. Participants received a 15 mg subcutaneous injection of ziltivekimab or a placebo once a month, on top of standard care ^[2].

The main measure was the time to a first major adverse cardiovascular event, or MACE: cardiovascular death, a non-fatal heart attack or a non-fatal stroke. Ziltivekimab did not reduce that risk compared with placebo. The hazard ratio was 0.99, with a 95% confidence interval of 0.88 to 1.11 ^[2].

The drug did have the biological effect researchers expected. It lowered free IL-6 and hsCRP, which Novo Nordisk described as evidence the drug reached its target ^[2]. In an earlier phase 2 study called RESCUE, ziltivekimab cut hsCRP by up to 92%, compared with 4% for placebo, in patients with moderate to severe kidney disease and elevated hsCRP ^[2].

"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, executive vice president, chief scientific officer and head of research and development at Novo Nordisk. "Although ziltivekimab produced the expected biological effect, this did not result in MACE benefits in this population" ^[2].

On safety, overall adverse events and serious adverse events were similar between the two arms of ZEUS, but a higher proportion of people taking ziltivekimab had serious infections. All-cause mortality did not differ between the arms ^[2]. Novo Nordisk said the safety description is based on topline data, and more detail is expected when full results are presented ^[2].

Financially, Novo Nordisk has said the ZEUS result will not change its previously communicated adjusted operating profit outlook for 2026, because the company will record the cost as a non-cash impairment charge in the third quarter of 2026 ^[2]. The size of that charge has not been disclosed. Full ZEUS results are scheduled for presentation at a scientific meeting in 2026 ^[2].

Why it matters for patients

Ziltivekimab is not an approved medicine. Both accounts describe it as experimental and in phase 3 testing, given as a monthly injection in trials ^[1][2]. Nothing in these results changes the approval status, labeling or supply of Novo Nordisk's GLP-1 medicines: Ozempic, Wegovy and Rybelsus are semaglutide, a different drug for different uses, and ziltivekimab is not part of those products.

People who joined HERMES or ATHENA will stop receiving the study injection ^[1]. What follow-up or transition care those participants will receive has not been reported.

The findings also test a research idea rather than a single product. Lowering inflammation through the IL-6 pathway did not produce fewer heart attacks, strokes or cardiovascular deaths in the ZEUS population, even though the drug measurably reduced inflammatory markers ^[2]. Whether that pattern holds in other groups of patients is the question the remaining trial is meant to answer.

Because the third-quarter charge is non-cash and sits outside the profit measure Novo Nordisk reports as adjusted, it does not represent cash leaving the business in that quarter, and the company has said its adjusted outlook for the year is unchanged ^[2]. What the setback means for the company's future spending on cardiovascular research has not been disclosed.

What happens next

• Full ZEUS results are expected at a scientific meeting in 2026 ^[2].
• ARTEMIS, which is testing ziltivekimab in people after an acute myocardial infarction, is the remaining trial in the program. It is expected to read out in the first half of 2027 ^[2]. HERMES had been listed for the same window before it was halted in September ^[2][1].
• The third-quarter 2026 impairment charge has been flagged but not sized ^[2].
• Whether Novo Nordisk will start further trials of ziltivekimab beyond ARTEMIS has not been reported.