Novo Nordisk Halts HERMES and ATHENA Trials of Ziltivekimab After Futility Finding

The company notified investigators on Friday that both trials were terminated. This follows the earlier ZEUS trial, which demonstrated that ziltivekimab lowered high-sensitivity C-reactive protein yet produced no reduction in major adverse cardiovascular events, including cardiovascular death, myocardial infarction, or stroke. The pattern indicates that biomarker suppression alone does not translate into clinical benefit when the antibody targets interleukin-6 signaling in patients with established atherosclerotic disease.

Similar results appeared in prior large programs. The CANTOS trial of canakinumab reduced events by 15 percent relative to placebo but carried an infection signal that limited uptake. Subsequent IL-6 or NLRP3 inhibitors have repeatedly shown discordance between inflammatory-marker reduction and hard outcomes, suggesting residual risk pathways or off-target effects not captured by current endpoints. Observational data linking chronic inflammation to events therefore overstate the causal fraction addressable by single-cytokine blockade.

The terminations narrow Novo Nordisk’s late-stage inflammation portfolio and raise questions about patient-selection criteria that rely solely on elevated CRP. Future studies will need enriched populations defined by genetic or imaging biomarkers, longer follow-up, or combination regimens. Regulatory precedent now favors trials that pre-specify both biomarker and clinical co-primary endpoints before large-scale investment.

Evidence quality remains limited to the single data-monitoring-committee decision and prior ZEUS readout; no peer-reviewed primary results have been released. The next required step is publication of the full futility analysis with event rates and subgroup data to determine whether any identifiable subset could still benefit.