Ziltivekimab: Why Were Two Heart Failure Trials Stopped?

Why is Novo Nordisk stopping the ziltivekimab heart failure trials?

Novo Nordisk confirmed that it is stopping two studies testing ziltivekimab in people with heart failure and inflammation. A company spokeswoman told Dow Jones that the decision followed a monitoring committee recommendation: the available evidence suggested a low likelihood of an outcome different from the unsuccessful ZEUS study. This is an assessment of the treatment's prospects, rather than a published numerical account of the two trials' final results. [Company explanation reported by Dow Jones](https://www.marketscreener.com/news/novo-nordisk-halts-two-heart-failure-studies-due-to-lack-of-efficacy-ce785bdbde8ff424).

The heart failure studies, HERMES and ATHENA, addressed different patient priorities. HERMES evaluated cardiovascular death, hospital admission for heart failure, or an urgent heart failure visit. ATHENA focused on changes in symptoms and physical limitations using a validated patient questionnaire. Both compared monthly ziltivekimab injections with placebo alongside standard care in adults with inflammation and preserved or mildly reduced heart pumping function. [Published HERMES and ATHENA designs](https://doi.org/10.1093/ejhf/xuag153).

How does ziltivekimab work, and what did the ZEUS trial show?

Ziltivekimab is a monoclonal antibody directed against interleukin-6, or IL-6. In July, Novo Nordisk reported that ZEUS, which enrolled more than 6,300 people with atherosclerotic cardiovascular disease, chronic kidney disease and inflammation, did not demonstrate a reduction in cardiovascular death, nonfatal heart attack or nonfatal stroke. The drug produced the expected changes in IL-6 and high-sensitivity C-reactive protein, an inflammation marker. [Novo Nordisk's ZEUS announcement](https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916587).

The distinction matters clinically: a blood test can show that a medicine affects its intended pathway without establishing that patients live longer or avoid serious illness. ZEUS also found more serious infections among ziltivekimab recipients, although overall adverse-event rates were similar between groups and all-cause mortality did not differ. Those findings concern ZEUS; they should not be presented as the final safety results of HERMES or ATHENA. The cited heart failure announcement attributes the stopping decision to the low likelihood of benefit. [ZEUS safety findings](https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916587).

Does this setback mean anti-inflammatory heart treatments cannot work?

Earlier research demonstrated that selectively targeting inflammation can reduce cardiovascular events in some circumstances. In the CANTOS randomized trial, published in The New England Journal of Medicine in 2017, canakinumab at the successful 150-mg dose reduced recurrent cardiovascular events in patients with a previous heart attack and elevated inflammation. However, canakinumab was associated with more fatal infections, and the trial did not demonstrate a significant reduction in overall mortality. Canakinumab targets interleukin-1 beta, a different inflammatory messenger from ziltivekimab's target. [CANTOS trial publication](https://doi.org/10.1056/NEJMoa1707914).

The reasonable interpretation is that targeting inflammation remains a specific therapeutic hypothesis requiring direct testing. Evidence from patients with previous heart attacks cannot establish benefit in people with chronic heart failure. Novo Nordisk says the separate ARTEMIS study, evaluating ziltivekimab in the acute period after a heart attack, will continue, with results expected in the first half of 2027. Its continuation leaves that question open; it does not predict a positive result. [Novo Nordisk's update reported by Dow Jones](https://www.marketscreener.com/news/novo-nordisk-halts-two-heart-failure-studies-due-to-lack-of-efficacy-ce785bdbde8ff424).