Novo Nordisk provides update on the ZEUS phase 3 trial in people with ASCVD, CKD and inflammation
Rhea-AI Summary
Novo Nordisk (NYSE:NVO) reported headline results from the phase 3 ZEUS cardiovascular outcomes trial of once‑monthly ziltivekimab 15 mg in over 6,300 people with ASCVD, CKD and inflammation (hsCRP ≥2 mg/L). Ziltivekimab showed IL‑6 pathway target engagement, with expected reductions in free IL‑6 and hsCRP, but did not reduce major adverse cardiovascular events (MACE) versus placebo (hazard ratio 0.99; 95% CI 0.88–1.11).
Overall adverse event and serious adverse event rates were similar between ziltivekimab and placebo, though serious infections were more frequent with ziltivekimab, and no difference in all‑cause mortality was observed. The outcome will trigger a non‑cash impairment charge in Q3 2026 but will not affect the company’s adjusted operating profit outlook for 2026. Ongoing cardiovascular outcomes trials HERMES (heart failure) and ARTEMIS (post‑acute heart attack) are planned to continue, with readouts expected in the first half of 2027.
Positive
- Overall AE and serious AE rates similar between ziltivekimab and placebo
- 2026 adjusted operating profit outlook unchanged despite ZEUS outcome
- Two additional ziltivekimab CVOTs (HERMES, ARTEMIS) continue with readouts expected H1 2027
Negative
- Primary endpoint missed: no MACE risk reduction vs placebo (HR 0.99; 95% CI 0.88–1.11)
- Higher serious infection rate in ziltivekimab group vs placebo
- Non‑cash impairment charge expected in Q3 2026 related to ZEUS outcome
Key Figures
Historical Context
| Date | Event | Sentiment | 24h Move | Catalyst |
|---|---|---|---|---|
| Mar 19 | FDA approval | Positive | -1.0% | FDA approved Wegovy HD after reported weight-loss results and expanded obesity treatment options. |
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
The available prior event showed a negative reaction to favorable FDA approval news, indicating divergence from the announcement's positive fundamentals.
Key Terms
hazard ratio medical
confidence interval medical
mace medical
monoclonal antibody medical
AI-generated analysis. How Rhea-AI works. Not financial advice.
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;
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.
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.
Contacts for further information
| Novo Nordisk Media: | |
| Ambre James-Brown +45 3079 9289 globalmedia@novonordisk.com | Liz Skrbkova (US) +1 609 917 0632 lzsk@novonordisk.com |
| Novo Nordisk Investors: | |
| Michael Novod +45 3075 6050 nvno@novonordisk.com | Sina Meyer +45 3079 6656 azey@novonordisk.com |
| Ida Schaap Melvold +45 3077 5649 idmg@novonordisk.com | Christoffer Togo Solgaard-Tullin +45 3079 1471 cftu@novonordisk.com |
| Alex Bruce +45 3444 2613 axeu@novonordisk.com | Mads Berner Bruun +45 3075 2936 mbbz@novonordisk.com |
| Frederik Taylor Pitter (US) +1 609 613 0568 fptr@novonordisk.com |
Company announcement No 45 / 2026
1 Time to first occurrence of 3-point MACE – primary endpoint analysis – Cox regression – in-study – full analysis set
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