Novo Nordisk’s $3.3 billion prospect fails clinical trial after showing no benefit over placebo

Novo Nordisk’s Phase 3 trial of ziltivekimab, a cardiovascular disease drug candidate that had been expected to become a multitrillion-won blockbuster, has failed.

According to Fierce Biotech on the 31st local time, Novo Nordisk said ziltivekimab failed to meet the primary endpoint in the Phase 3 Zeus trial, which enrolled more than 6,300 patients with atherosclerotic cardiovascular disease and chronic kidney disease (CKD).

The trial evaluated whether monthly subcutaneous injections of ziltivekimab, an antibody targeting the IL-6 ligand, could suppress cardiovascular inflammation and reduce major adverse cardiovascular events (MACE), including heart attacks and strokes. However, the ziltivekimab group did not show a statistically significant reduction compared with the placebo group in the incidence of cardiovascular death, nonfatal heart attack or nonfatal stroke.

Market analysts, including Guggenheim Securities, had placed high odds on clinical success and expected a 15% improvement (hazard ratio, 0.85). However, the actual hazard ratio (HR) was 0.99, indicating essentially no difference in efficacy from placebo.

With this failure, Novo Nordisk has lost an important opportunity to diversify its obesity- and diabetes-focused portfolio. The industry had estimated ziltivekimab’s peak annual sales at approximately $3 billion (about 4.5 trillion won).

Ziltivekimab’s fate will depend on two other trials, with results scheduled for release in the first half of next year. The Hermes trial in patients with heart failure and the Artemis trial in patients with acute heart attacks are currently underway.

However, analysts at BMO Capital Markets assessed that the remaining two trials are also unlikely to produce positive results following the failure of the Zeus trial. They said the pipeline failure could increase Novo Nordisk’s interest in mergers and acquisitions (M&A), potentially helping reduce its excessive concentration on the GLP-1 business.