Anti-inflammation drug fails to protect the aging heart
A promising strategy to fight cardiovascular disease by dampening inflammation appears to have faltered again. Novo Nordisk halted two large trials of its drug ziltivekimab after an independent monitoring committee concluded that success was unlikely.
Chronic low-grade inflammation is known to contribute to the development and progression of cardiovascular disease. This understanding has fuelled hopes that drugs reducing inflammation might also prevent heart attacks and strokes. Ziltivekimab targets a protein called interleukin-6 (IL-6), one of the central signalling molecules in the inflammatory process.
The researchers at Novo Nordisk halted the HERMES and ATHENA trials following an interim analysis. The decision follows the earlier failure in the ZEUS trial, in which ziltivekimab lowered blood markers of inflammation but did not reduce the risk of major cardiovascular events such as death or heart attacks.
A pattern of disappointments
This is not the first time an anti-inflammation approach has failed in cardiovascular disease. Earlier drugs targeting other inflammatory pathways have produced mixed results. Lowering an inflammation marker in the blood, such as CRP or IL-6, does not automatically translate into fewer heart attacks. This suggests that chronic inflammation in cardiovascular disease may be a consequence rather than a cause, or that the right targets have not yet been found.
For the longevity field, where inflammaging, the chronic inflammation that accumulates with age, is widely viewed as a therapeutic target, this is an important lesson. Not every mechanism that seems biologically logical translates into clinical benefit.
What happens next
The ziltivekimab failures increase pressure to better understand which patients might benefit from anti-inflammatory therapies and which would not. Subgroup analyses of existing data may still yield insights. Other companies are pursuing similar approaches, but the balance of evidence is shifting.
Search terms to explore further: interleukin-6 inhibition cardiovascular risk, inflammaging heart disease clinical trial, anti-inflammatory therapy cardiovascular endpoints