Why did Novo Nordisk’s heart drug fail? A major Phase 3 trial found the anti-inflammatory therapy lowered inflammation but not cardiovascular risk.
Novo Nordisk, the maker of blockbuster diabetes and weight-loss drugs Ozempic and Wegovy, has suffered a major setback after its experimental anti-inflammatory heart drug ziltivekimab failed to reduce the risk of major cardiovascular events in a large late-stage clinical trial.
The disappointing results have cast doubt on the company’s efforts to expand beyond obesity and diabetes into cardiovascular disease, sending its shares sharply lower. ()
The Phase 3 ZEUS trial enrolled more than 6,300 patients with atherosclerotic cardiovascular disease, chronic kidney disease, and persistent inflammation. Researchers hoped the once-monthly injection would reduce the risk of cardiovascular death, heart attack, and stroke by targeting chronic inflammation, a factor increasingly recognized as a driver of heart disease.
Heart Drug Failed to Cut Heart Attack and Stroke Risk
The trial produced a mixed outcome. Ziltivekimab successfully lowered inflammatory markers, including interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP), confirming that the drug was hitting its intended biological target. However, those improvements did not translate into fewer heart attacks, strokes, or cardiovascular deaths.
The study reported a hazard ratio of 0.99, showing virtually no difference between patients receiving the drug and those given a placebo. Researchers also observed a higher rate of serious infections among patients taking ziltivekimab, although overall mortality remained similar between the two groups.
Novo Nordisk’s Chief Scientific Officer Martin Holst Lange said the study achieved the expected biological effect but failed to deliver the clinical benefit researchers had hoped for. The company said the findings would help guide future cardiovascular research.
Failed Trial Deals Blow to Novo Nordisk’s Expansion Plans
The failed trial represents more than just the loss of a promising drug candidate. Novo Nordisk has been working to diversify beyond its highly successful GLP-1 medicines by investing heavily in cardiovascular and metabolic diseases. The company acquired ziltivekimab through its $725 million purchase of Corvidia Therapeutics in 2020, viewing the drug as a potential growth opportunity outside diabetes and obesity.
Following the announcement, Novo Nordisk’s shares fell by around 7–10%, reflecting investor concerns about the company’s broader research pipeline. Analysts say the setback could increase pressure on Novo Nordisk to strengthen its portfolio through acquisitions or partnerships in cardiovascular medicine and other therapeutic areas.
The study was also seen as an important test of a broader scientific theory—that reducing inflammation could lower the risk of future cardiovascular events.
Novo Nordisk Presses Ahead Despite Trial Setback
Although earlier studies had shown encouraging reductions in inflammatory biomarkers, the ZEUS trial suggests that lowering those markers alone may not be enough to improve long-term cardiovascular outcomes in this patient population. The findings are expected to influence future research into anti-inflammatory therapies for heart disease and how scientists evaluate potential treatments.
Novo Nordisk says it is not abandoning ziltivekimab. Two ongoing Phase 3 studies—HERMES, involving patients with heart failure, and ARTEMIS, involving patients recovering from acute heart attacks—will continue as planned. Results from both trials are expected in the first half of 2027.
The company also said the failed ZEUS trial will not affect its financial guidance for 2026, although it expects to record a non-cash impairment charge in the third quarter related to the drug’s value.
While the setback is significant, Novo Nordisk maintains that cardiovascular disease remains a strategic priority. Whether future trials can deliver the clinical benefits that ZEUS could not will now be closely watched by investors, physicians, and the pharmaceutical industry alike.
References:
- Novo Nordisk provides update on the ZEUS phase 3 trial in people with ASCVD, CKD and inflammation – (https://www.globenewswire.com/news-release/2026/07/31/3336733/0/en/novo-nordisk-provides-update-on-the-zeus-phase-3-trial-in-people-with-ascvd-ckd-and-inflammation.html)
Source-Medindia