Novartis keeps its IL-6 bet alive after Novo Nordisk trial failure

Novo Nordisk’s Phase 3 ZEUS trial of ziltivekimab failed to reduce major adverse cardiovascular events—including cardiovascular death, nonfatal heart attack, or stroke—in more than 6,300 high-risk patients. The drug lowered IL-6 and hs-CRP, confirming biological activity, but produced essentially no clinical benefit versus placebo (hazard ratio 0.99).

Novartis is nevertheless advancing pacibekitug, its acquired IL-6-targeting antibody. In the Phase 2 TRANQUILITY study, quarterly doses produced sustained hs-CRP reductions of roughly 75%–86% in patients with chronic kidney disease and elevated inflammation.

The companies’ approaches differ:
ziltivekimab targets the IL-6 receptor and was administered monthly, while pacibekitug directly binds IL-6 and is designed for quarterly dosing.

Novartis and its former asset owner Tourmaline Bio argue that Novo’s failure does not invalidate the broader inflammation hypothesis. The companies may pursue a different patient population, dosing schedule, or disease setting, but pacibekitug still needs to demonstrate that biomarker reductions translate into fewer cardiovascular events.

The setback highlights a central risk in anti-inflammatory cardiovascular drug development:
reducing inflammation markers such as CRP is not sufficient evidence of improved outcomes. IL-6 blockade may also carry infection-related safety concerns; serious infections were more frequent with ziltivekimab.

Novartis paid about $1.4 billion to acquire Tourmaline Bio and pacibekitug in 2025. The asset is expected to move toward Phase 3 testing, while Novo plans to continue two other ziltivekimab studies, with results expected in the first half of 2027.