Novo Nordisk drug shows no MACE benefit in ZEUS trial

Novo Nordisk A/S reported headline results from the ZEUS phase 3 cardiovascular outcomes trial of ziltivekimab in more than 6,300 people with atherosclerotic cardiovascular disease, chronic kidney disease and inflammation.

Rhea-AI Filing Summary

Novo Nordisk A/S reported headline results from the ZEUS phase 3 cardiovascular outcomes trial of ziltivekimab in more than 6,300 people with atherosclerotic cardiovascular disease, chronic kidney disease and inflammation. Ziltivekimab reduced free IL‑6 and hsCRP as expected, but did not lower major adverse cardiovascular events versus placebo (hazard ratio 0.99; 95% confidence interval 0.88 to 1.11).

Overall adverse-event rates were similar between groups, although serious infections were more frequent with ziltivekimab; no difference in all-cause mortality was seen. Novo Nordisk plans to continue the HERMES and ARTEMIS cardiovascular trials, with results anticipated in the first half of 2027. The ZEUS outcome will not change the company’s adjusted operating profit outlook for 2026 but will trigger a non-cash impairment charge in Q3 2026.

Positive

• None.

Negative

• ZEUS phase 3 did not reduce MACE risk for ziltivekimab versus placebo, with a hazard ratio of 0.99 (95% CI 0.88–1.11) in people with ASCVD, CKD and inflammation.
• A non-cash impairment charge in Q3 2026 will result from the ZEUS outcome, even though Novo Nordisk’s previously communicated adjusted operating profit outlook for 2026 remains unchanged.

Key Figures

MACE hazard ratio: 0.99 95% CI lower bound: 0.88 95% CI upper bound: 1.11 +5 more

8 metrics

MACE hazard ratio 0.99 Ziltivekimab versus placebo in the ZEUS cardiovascular outcomes trial

95% CI lower bound 0.88 Lower limit of the 95% confidence interval for the ZEUS MACE hazard ratio

95% CI upper bound 1.11 Upper limit of the 95% confidence interval for the ZEUS MACE hazard ratio

Trial enrollment over 6,300 people Participants with ASCVD, CKD and inflammation in the ZEUS phase 3 trial

hsCRP inclusion threshold ≥2 mg/L Inflammation criterion for ZEUS enrollment based on hsCRP level

Ziltivekimab dose 15 mg Once-monthly subcutaneous ziltivekimab dose tested versus placebo in ZEUS

Employees about 68,800 people Novo Nordisk global workforce as described in the company profile

Countries marketed in around 170 countries Number of countries where Novo Nordisk markets its products

Key Terms

major adverse cardiovascular events (MACE), high-sensitivity C-reactive protein (hsCRP), atherosclerotic cardiovascular disease (ASCVD), heart failure with preserved ejection fraction (HFpEF), +1 more

5 terms

major adverse cardiovascular events (MACE) medical

"did not translate into major adverse cardiovascular events (MACE) risk reduction"

Major adverse cardiovascular events (MACE) is a medical shorthand for a group of the most serious heart- and blood-vessel related outcomes—typically heart attack, stroke, and cardiovascular death—used together as a single measure in studies and reports. Investors care because MACE rates summarize a therapy’s or device’s real-world safety and effectiveness for preventing life‑threatening events; like a single report card grade, they influence regulatory approval, prescribing, liability risk, and market adoption.

high-sensitivity C-reactive protein (hsCRP) medical

"reductions in free IL-6 and high-sensitivity C-reactive protein (hsCRP) respectively"

atherosclerotic cardiovascular disease (ASCVD) medical

"people with atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD)"

Atherosclerotic cardiovascular disease (ASCVD) is the long-term narrowing and hardening of arteries caused by buildup of fatty plaques, which can block blood flow and lead to heart attacks, strokes or limb problems—think of arteries as pipes that become clogged over time. It matters to investors because ASCVD drives demand for drugs, medical devices, diagnostic tests and long-term care, influences healthcare costs and regulatory scrutiny, and affects the market potential and revenue forecasts for companies in healthcare and insurance.

heart failure with preserved ejection fraction (HFpEF) medical

"heart failure with preserved ejection fraction (HFpEF)"

Market Abuse Regulation regulatory

"Publication of inside information pursuant to Market Abuse Regulation, Article 17"

Market abuse regulation consists of laws and rules designed to prevent dishonest or manipulative practices in financial markets. It aims to ensure fair and transparent trading, so investors can trust that markets operate honestly, much like rules that keep a game fair. By reducing unfair advantages, it helps protect investor confidence and promotes healthy, efficient markets.

FAQ

AI-generated questions and answers. How Rhea-AI works. Not financial advice.

What did Novo Nordisk (NVO) report about the ZEUS phase 3 trial?

Novo Nordisk reported headline ZEUS results showing that while ziltivekimab reduced markers of inflammation, it did not reduce major adverse cardiovascular events versus placebo (hazard ratio 0.99; 95% CI 0.88–1.11) in people with ASCVD, CKD and inflammation.

Did ziltivekimab lower MACE risk for Novo Nordisk (NVO) in ZEUS?

No. Ziltivekimab did not lower major adverse cardiovascular events (MACE) risk compared with placebo in ZEUS, with a hazard ratio of 0.99 and a 95% confidence interval from 0.88 to 1.11, indicating no meaningful risk reduction.

How many patients were enrolled in Novo Nordisk's (NVO) ZEUS trial and what was studied?

ZEUS enrolled over 6,300 people with atherosclerotic cardiovascular disease, chronic kidney disease and inflammation, defined by hsCRP ≥2 mg/L. It tested once-monthly subcutaneous ziltivekimab 15 mg versus placebo for reducing MACE, including cardiovascular death, non-fatal heart attack and non-fatal stroke.

What were the key safety findings from the ZEUS trial for Novo Nordisk (NVO)?

Overall rates of adverse events and serious adverse events were similar between ziltivekimab and placebo. However, in line with IL‑6 inhibition, a higher proportion of serious infections occurred with ziltivekimab, while no difference in all-cause mortality was observed.

Will the ZEUS trial outcome affect Novo Nordisk's (NVO) 2026 financial outlook?

Novo Nordisk stated that ZEUS will not impact its previously communicated adjusted operating profit outlook for 2026. The company does, however, expect to record a non-cash impairment charge in Q3 2026 related to the trial outcome.

What are the next steps for ziltivekimab in Novo Nordisk's (NVO) cardiovascular program?

Novo Nordisk will continue two ongoing cardiovascular outcomes trials with ziltivekimab: HERMES in heart failure and ARTEMIS after acute heart attack. These studies are planned to continue and are anticipated to read out in the first half of 2027.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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Available on EDGAR 07/31/2026 - 08:55 AM Accepted by SEC EDGAR 07/31/2026 - 08:54 AM Learn about SEC filing dates

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

________________

FORM 6-K

________________

REPORT OF FOREIGN PRIVATE ISSUER

Pursuant to Rule 13a-16 or 15d-16

of the Securities Exchange Act of 1934

July 31, 2026

________________

NOVO NORDISK A/S

 (Exact name of Registrant as specified in its charter)

Novo Allé 1

DK- 2880, Bagsvaerd

Denmark

(Address of principal executive offices)

________________

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F

Form 20-F ☒           Form 40-F ☐

 

 

Novo Nordisk provides update on the ZEUS phase 3 trial in people with ASCVD, CKD and inflammation

Bagsværd, Denmark, 31 July 2026 – Novo Nordisk today announced headline results from the ZEUS cardiovascular outcomes 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)1.

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.

“ZEUS was designed to test whether inhibition of the IL-6 pathway could translate reductions in cardiovascular inflammation into fewer major cardiovascular events. Although ziltivekimab produced the expected biological effect, this did not result in MACE benefits in this population,” said Martin Holst Lange, executive vice president, chief scientific officer and head of Research and Development at Novo Nordisk. “While ziltivekimab did not achieve the MACE benefit we had hoped for, this does not change our strategic commitment to cardiovascular disease. The study provides important scientific evidence that will inform our ongoing cardiovascular research and the development of treatments for patients who continue to face substantial unmet need.”

Overall rates of adverse events (AEs) and serious AEs 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.

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The two additional ongoing cardiovascular outcomes trials investigating ziltivekimab in people with heart failure (HERMES) and in people following an acute heart attack (ARTEMIS) are planned to continue and are anticipated to read out in the first half of 2027.

The outcome of ZEUS will not impact Novo Nordisk’s previously communicated adjusted operating profit outlook for 2026 but will result in a non-cash impairment charge in Q3 2026.

Full results of the ZEUS trial will be presented at an upcoming scientific meeting in 2026.

About ziltivekimab

Ziltivekimab is an investigational, fully human monoclonal antibody that targets the IL-6 ligand, a pro-inflammatory cytokine, to reduce cardiovascular inflammation and improve cardiovascular outcomes. It is being developed by Novo Nordisk for conditions such as cardiovascular disease, acute myocardial infarction (AMI) and heart failure with preserved ejection fraction (HFpEF).

About ZEUS

ZEUS – an event-driven cardiovascular outcomes trial investigating efficacy and safety with once-monthly subcutaneous ziltivekimab 15 mg versus placebo on top of standard of care in people with atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and CV inflammation (hsCRP ≥ 2 mg/L).

Novo Nordisk is a leading global healthcare company founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines and working to prevent and ultimately cure disease. Novo Nordisk employs about 68,800 people in 80 countries and markets its products in around 170 countries. Novo Nordisk's B shares are listed on Nasdaq Copenhagen (Novo-B). Its ADRs are listed on the New York Stock Exchange (NVO). For more information, visit novonordisk.com, Facebook, Instagram, X, LinkedIn and YouTube.

Publication of inside information pursuant to Market Abuse Regulation, Article 17.

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Contacts for further information
Novo Nordisk Media:
Ambre James-Brown	Liz Skrbkova (US)
+45 3079 9289	+1 609 917 0632
globalmedia@novonordisk.com	lzsk@novonordisk.com
Novo Nordisk Investors:
Michael Novod	Sina Meyer
+45 3075 6050	+45 3079 6656
nvno@novonordisk.com	azey@novonordisk.com
Ida Schaap Melvold	Christoffer Togo Solgaard-Tullin
+45 3077 5649	+45 3079 1471
idmg@novonordisk.com	cftu@novonordisk.com
Alex Bruce	Mads Berner Bruun
+45 3444 2613	+45 3075 2936
axeu@novonordisk.com	mbbz@novonordisk.com
Frederik Taylor Pitter (US)
+1 609 613 0568
fptr@novonordisk.com

Novo Nordisk A/S Investor Relations	Novo Allé 1 2880 Bagsværd Denmark	Telephone: +45 4444 8888	www.novonordisk.com CVR no: 24 25 67 90
			Company announcement No 45 / 2026

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf of the undersigned, thereunto duly authorized.

Date: July 31, 2026   NOVO NORDISK A/S   Maziar Mike Doustdar Chief Executive Officer