Novo Nordisk has ended two more late-stage trials of its experimental heart drug ziltivekimab, and the thousands of heart failure patients enrolled in those studies will stop receiving the monthly injection they signed up for. The company told investigators on September 4 that the HERMES and ATHENA trials would close early, and the decision became public on September 7.
An independent data monitoring committee recommended the stop. According to a company statement given to Clinical Trials Arena, the committee reviewed the totality of the data and concluded both studies were unlikely to reach a different outcome than the ZEUS trial, which missed its primary endpoint in July. This is a futility stop, not a safety stop. The two are not the same thing, and the distinction matters for the people enrolled.
For those patients and their families, the practical consequence lands this month. Trial sites will begin closeout visits, monthly injections will end, and participants will return to standard heart failure care. Nobody in either study will find out whether they received the drug or a placebo until the sponsor unblinds the data, and no approved therapy has been withdrawn from the market as a result of any of this.
The Data Monitoring Committee's Call
HERMES and ATHENA were both Phase 3 studies testing monthly ziltivekimab 15 mg against placebo in people with heart failure with preserved or mildly reduced ejection fraction, elevated natriuretic peptide levels and evidence of cardiovascular inflammation. As designed, HERMES planned to enroll about 4,900 participants and ATHENA about 680.
The two studies asked different questions. HERMES measured hard outcomes, with a primary endpoint combining cardiovascular death, hospitalization for heart failure and urgent heart failure visits. ATHENA measured symptoms, physical function and health status. Stopping both at once signals that the monitoring committee saw no separation on either front, on outcomes or on how patients felt and functioned day to day. Trials are sometimes halted on one measure while another continues, and that did not happen here.
Ziltivekimab is a fully human monoclonal antibody that targets the interleukin-6 ligand, a protein that drives inflammation. The scientific bet was that lowering cardiovascular inflammation would translate into fewer clinical events. ZEUS tested that idea in more than 6,300 people with atherosclerotic cardiovascular disease and chronic kidney disease. The drug did what it was designed to do biologically, reducing free interleukin-6 and high-sensitivity C-reactive protein, but the hazard ratio for major adverse cardiovascular events came in at 0.99, with a 95 percent confidence interval running from 0.88 to 1.11. That is a null result.
Martin Holst Lange, Novo Nordisk's executive vice president, chief scientific officer and head of research and development, said at the time that the outcome "does not change our strategic commitment to cardiovascular disease," according to the company's ZEUS announcement. The company also disclosed that serious infections occurred more often with ziltivekimab than with placebo, and that no difference in all-cause mortality was observed.
Patients Left Without a Study Drug
Heart failure with preserved ejection fraction accounts for a large share of all heart failure cases and has far fewer proven treatments than the reduced ejection fraction form. That scarcity is why enrollment in these trials was attractive to patients in the first place, and why an early stop is more than a corporate setback for the people involved.
Participants should expect a call or letter from their study site rather than acting on news coverage. The steps that follow are routine: a closeout visit, a return to guideline-directed therapy under a treating cardiologist, and no abrupt change to any prescription medication already being taken. Anyone enrolled should keep taking their regular heart failure medicines unless a clinician instructs otherwise.
There is a second group affected less directly. Inflammation blood tests, particularly high-sensitivity C-reactive protein, are increasingly ordered at routine checkups, and patients who have been told their inflammation is elevated may reasonably wonder what these results mean for them. The honest answer is that lowering the marker did not lower the risk in these trials. That does not make the marker useless for estimating risk, but it does undercut the idea that driving the number down with this class of drug produces a clinical benefit.
Cost and access are not immediately affected. Ziltivekimab has never been approved in any country, was never available outside a study, and cannot be prescribed. No guideline has changed, and no insurance coverage decision turns on this news.
One Trial Still Standing
The ARTEMIS trial continues as planned. It is testing ziltivekimab in patients recovering from an acute heart attack, a different clinical setting with a different inflammatory profile, and results are expected in the first half of 2027. Novo Nordisk has said that the study remains on track.
Several things are still unknown. Full data from HERMES and ATHENA have not been published or peer-reviewed, and the topline information released so far comes from the sponsor, with the halt first reported by STAT and other outlets. Whether the failures reflect the specific drug or the entire strategy of blocking interleukin-6 in heart disease will not be settled until more results are in. Novo Nordisk has not detailed what the closures mean for its financial outlook beyond the non-cash impairment charge it already flagged for the third quarter of 2026.
The next milestones to watch are the presentation of full ZEUS results at a scientific meeting, publication of the HERMES and ATHENA data, and the ARTEMIS readout next year.
MedicalDaily previously reported on the failure of the ZEUS trial and what it meant for the inflammation theory of artery disease.
Key Questions Answered
What exactly did Novo Nordisk stop? The HERMES and ATHENA Phase 3 trials of ziltivekimab in heart failure. Investigators were told on September 4, and the news became public on September 7.
Why were the trials stopped? An independent data monitoring committee reviewed the data and concluded both studies were unlikely to produce a different result than the failed ZEUS trial. It was a futility decision, not a safety recall.
How many patients were involved? HERMES was designed to enroll about 4,900 participants and ATHENA about 680, so roughly 5,500 people were planned across the two studies.
Should trial participants stop their other heart medications? No. Participants should wait for instructions from their study site and continue prescribed heart failure medicines unless a treating clinician says otherwise.
Was ziltivekimab available by prescription? No. It was never approved in any country and was available only inside clinical studies.
Does this change what an elevated inflammation test means? It does not change the value of hs-CRP for estimating risk, but these trials found that lowering the marker with this drug did not reduce clinical events.
What happens next? The ARTEMIS trial in post-heart attack patients continues, with results expected in the first half of 2027. Full HERMES and ATHENA data have not yet been published.
