ZEUS failure clouds future of Novo’s cardiovascular plans

Why it matters: The setback weakens Novo’s attempt to build a cardiovascular business beyond its obesity and diabetes portfolio. It also leaves two studies expected next year carrying the remaining prospects of the ziltivekimab program.

Zoom in: The ZEUS trial enrolled more than 6,300 people with atherosclerotic cardiovascular disease, chronic kidney disease and inflammation. Participants received either a monthly 15 mg injection of ziltivekimab or placebo on top of standard care.

• Ziltivekimab produced the expected reductions in free interleukin-6 and high-sensitivity C-reactive protein, confirming that the drug affected its intended inflammatory pathway.
• However, it did not significantly reduce cardiovascular death, nonfatal heart attack or nonfatal stroke (MACE). The hazard ratio was 0.99, meaning the event risk was virtually identical between the treatment and placebo groups.

What they’re saying: “ZEUS was designed to test whether inhibition of the IL-6 pathway could translate reductions in cardiovascular inflammation into fewer major cardiovascular events. Although ziltivekimab produced the expected biological effect, this did not result in MACE benefits in this population,” said Martin Holst Lange, Novo’s chief scientific officer and head of R&D.

Reality check: Overall rates of adverse events and serious adverse events were similar between the groups, but serious infections were more common among patients receiving ziltivekimab. Novo said there was no difference in deaths from all causes.

Backstory: Novo obtained ziltivekimab through its 2020 acquisition of French biotech Corvidia Therapeutics. The deal included $725 million upfront and was potentially worth $2.1 billion.

What’s next: Novo will continue two other cardiovascular outcome trials. HERMES is evaluating ziltivekimab in heart failure, while ARTEMIS is testing it in patients following an acute heart attack.

• Both are expected to report results in the first half of 2027. However, several analysts see in the ZEUS failure that positive results from either trial are unlikely.