Novo shuts two more ziltivekimab heart trials, and analysts write off IL-6
Novo Nordisk halted two more Phase 3 heart failure trials of ziltivekimab after its July failure in ZEUS, ending the company's clearest attempt to build a heart-disease franchise outside GLP-1 drugs.
Novo Nordisk is ending two more late-stage trials of ziltivekimab, its experimental interleukin-6 (IL-6) inhibitor, after independent monitors concluded the studies were unlikely to succeed. The company told BioSpace on Sept. 8, 2026 that it is stopping the Phase 3 HERMES and ATHENA heart failure trials early [1].
A Novo spokesperson said the decision was "based on a recommendation from the Data Monitoring Committee on the totality of the data (including the low likelihood of a different outcome from ZEUS)" [1]. HERMES had enrolled nearly 5,000 patients with heart failure with mildly reduced ejection fraction plus systemic inflammation; ATHENA had recruited 680 patients with the same type of heart failure [1].
What ZEUS showed
The trouble started on July 31, 2026, when ziltivekimab missed its primary endpoint in ZEUS, the first of three Phase 3 trials to report. In more than 6,300 patients with atherosclerotic cardiovascular disease, chronic kidney disease and elevated inflammation, the drug did not significantly reduce major adverse cardiovascular events compared with placebo [2]. Novo's shares fell close to 9 percent that day and roughly $30 billion in market value evaporated [2]. The company said its 2026 adjusted operating profit outlook was unchanged, but that a non-cash impairment charge would land in the third quarter [2].
After ZEUS, some in the industry argued the miss might have been about which patients were enrolled rather than the drug's biology. Oppenheimer analysts wrote on Sept. 8 that the futility terminations of HERMES and ATHENA "remove the population-selection defense," and that "IL-6 now looks like an invalid target in chronic cardiovascular disease" [1].
Ziltivekimab's collapse is part of a broader run of setbacks. Oppenheimer counted six high-profile cardiovascular trial failures in nine weeks, including AstraZeneca and Ionis' Wainua in transthyretin-mediated amyloid cardiomyopathy, Novartis' pelacarsen, and Tenax Therapeutics' oral levosimendan [1]. Together the results have fed a narrative that cardiovascular outcome trials "are becoming unwinnable," though Oppenheimer said the trials differed enough in design and population that a deeper framing is needed [1].
One ziltivekimab study is still running. ARTEMIS is testing the drug in the acute setting after a heart attack, and Novo says it will continue as planned with a readout slated for the first half of next year [1]. BMO analysts wrote that "ARTEMIS remains active with lower expectations for success" [1]. Novo's stock dipped 2 percent to $45.59 on Sept. 8 [1].
Why it matters for patients
Ziltivekimab is not a weight-loss or diabetes drug. It was designed to lower cardiovascular risk by calming inflammation, a completely different route than GLP-1 medicines like semaglutide. For people with obesity, diabetes, kidney disease or heart failure who were hoping for a new non-GLP-1 option aimed at heart events, that option now looks much further away — and, based on the analyst reading of the data, may not arrive from this drug class at all [1].
It also matters strategically. Ziltivekimab was Novo's clearest attempt to build a cardiometabolic franchise that does not depend on GLP-1, and that diversification is now a year or more further away [2]. What remains in Novo's later-stage metabolic pipeline includes CagriSema, the once-weekly GLP-1 plus amylin combination that produced about 22.7 percent weight loss and faces an FDA decision in the second half of 2026, and amycretin, still in Phase 3 [2].
Patients enrolled in HERMES and ATHENA are directly affected, since both studies are being stopped early [1]. The sources do not say how those participants will be followed or what, if anything, Novo will report from the partial data. That is not yet known.
What happens next
Sources
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