Canakinumab Cuts Cardiovascular Risk Via Reduced Inflammation

Canakinumab (ACZ885) injections lower the risk of cardiovascular disease and lung cancer risk through inflammation reduction, according to results of the CANTOS trial’s examination of the IL-1β inhibitor.

The results of the trial, led by Paul Ridker (pictured), MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston, were presented at the European Society of Cardiology (ESC) Congress, in Barcelona, Spain, and published in the New England Journal of Medicine.

10061 patients who had previously had myocardial infarction with persistently high levels of sensitivity to C-reactive protein (hsCRP) were selected to receive either placebo, 50, 150, or 300 mg of subcutaneous canakinumab every 3 months, in addition to aggressive standard care. Patients were followed for up to 4 years.

At doses of 150 or 300 mg, canakinumab reduced cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death) risk by 15% and 14%, respectively (HR 0.85; 95% CI, 0.74-0.98; p=0.021 and HR 0.86; 95% CI, 0.75-0.99; p=0.031, respectively).

The secondary endpoint — the first occurrence of cardiovascular events or hospitalization for unstable angina requiring urgent revascularization – was reduced by 17% in the 150 mg and 300 mg groups (HR 0.83; 95% CI, 0.73-0.95; p=0.005 and HR 0.83; 95% CI, 0.72-0.94; p=0.004, respectively).

“These findings represent the end game of more than two decades of research, stemming from a critical observation that half of heart attacks occur in people who do not have high cholesterol,” Ridker said in a statement. “For the first time, we’ve been able to definitively show that lowering inflammation independent of cholesterol reduces cardiovascular risk.”

Canakinumab suppresses inflammation by neutralizing interleukin-1β signaling, usually used to treat rare inherited conditions that are associated with IL-1β overproduction. Overall, canakinumab was found to be safe, although 1 in 1000 patients had a possibly fatal infection.

The drug was found to have no effect on cholesterol despite the reduction in inflammation. The drug was also found to dramatically reduce total cancer death rates — especially lung cancer – but the effects were dose-dependent.

“This has far-reaching implications,” Ridker said. “By leveraging an entirely new way to treat patients — targeting inflammation – we may be able to significantly improve outcomes for certain very high-risk populations.”

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