Novo Nordisk halts two more heart failure trials of ziltivekimab

Novo Nordisk has halted two more Phase 3 trials of ziltivekimab, an experimental anti-inflammatory medicine the company had been testing against heart disease ^[1].

The two studies, HERMES and ATHENA, were both in heart failure. HERMES had signed up close to 5,000 people whose hearts pumped only mildly below the normal range and who also showed signs of systemic inflammation. ATHENA enrolled 680 people with the same form of heart failure ^[1].

A company spokesperson told BioSpace the stop decision followed a recommendation from the trials' Data Monitoring Committee, which weighed "the totality of the data (including the low likelihood of a different outcome from ZEUS)" ^[1].

ZEUS is the study that set this in motion. Reported July 31, 2026, it covered more than 6,300 patients with atherosclerotic cardiovascular disease, chronic kidney disease and elevated inflammation. Ziltivekimab did not significantly reduce major adverse cardiovascular events compared with placebo ^[2]. Novo shares fell close to 9% that day, erasing roughly $30 billion in market value ^[2]. The company said its 2026 adjusted operating profit outlook was unchanged and that a non-cash impairment charge would be booked in the third quarter ^[2].

Some observers had suggested the ZEUS result might reflect the particular mix of patients in that study rather than the drug's mechanism. Ending HERMES and ATHENA undercuts that argument. "IL-6 now looks like an invalid target in chronic cardiovascular disease," analysts at Oppenheimer wrote on Sept. 8. The two new terminations "remove the population-selection defense," they said ^[1].

Oppenheimer counted six high-profile cardiovascular setbacks in nine weeks. Alongside Novo's three ziltivekimab trials, the firm listed Wainua, from AstraZeneca and Ionis Pharmaceuticals, which did not significantly help patients with transthyretin-mediated amyloid cardiomyopathy; Novartis' pelacarsen, which showed no significant benefit on cardiovascular risk in a late-stage study; and Tenax Therapeutics' oral levosimendan in pulmonary hypertension caused by heart failure with preserved ejection fraction ^[1]. The run has fed a narrative that cardiovascular outcome trials "are becoming unwinnable," the analysts wrote, though they noted the studies tested different conditions in different groups of people ^[1].

Novo's stock was down 2% at $45.59 a share after the market opened Tuesday ^[1].

Why it matters for patients

Ziltivekimab is not approved for any use, so it was only available to people who joined a research study ^[1]. There was never a prescription to fill or a dose to adjust, and nothing announced this week changes a medicine patients already take.

What the news does signal is a narrowing of Novo's pipeline beyond weight loss and diabetes. Ziltivekimab was the company's clearest route to a heart-and-metabolism business that did not rest on GLP-1 drugs, and that diversification is now a year or more further off ^[2]. Novo had already absorbed a 2026 disappointment when CagriSema, its once-weekly GLP-1 and amylin combination for weight management, produced about 22.7% weight loss against expectations of roughly 25% ^[2].

People enrolled in HERMES and ATHENA have not been told publicly what comes next. Whether participants will keep receiving the drug, be switched to another therapy, or stop treatment altogether has not been disclosed.

What happens next

A third Phase 3 trial, ARTEMIS, is still active. It tests ziltivekimab in the period right after a heart attack, and results are expected in the first half of next year ^[1]. BMO analysts wrote that "ARTEMIS remains active with lower expectations for success" ^[1].

BMO flagged Novo's Capital Markets Day on Sept. 21 as the next event investors will watch ^[1]. Separately, a US regulatory decision on CagriSema is expected in the second half of 2026 ^[2], and it now stands as one of the company's nearer-term pipeline milestones.