A new phase 3 trial published in the Journal of American College of Cardiology has found that inclisiran significantly reduces low-density lipoprotein cholesterol (LDL-C) levels compared to both ezetimibe and placebo in adults without a history of atherosclerotic cardiovascular disease (ASCVD).

The VICTORION-Mono (V-Mono) trial enrolled 350 adults aged 18–75 years who had never taken lipid-lowering therapy and were free from ASCVD, diabetes, or familial hypercholesterolemia. All participants had a fasting LDL-C between 100 and 190 mg/dL and a low predicted 10-year ASCVD risk (<7.5%).

Participants were randomly assigned to receive inclisiran (n = 174), ezetimibe (n = 89), or placebo (n = 87). The primary endpoint was the percentage change in LDL-C from baseline to day 150.

Results showed that inclisiran monotherapy reduced LDL-C by 46.5% on average, compared to just 11.2% for ezetimibe and a 1.4% increase with placebo. The LDL-C reduction was significantly greater with inclisiran than both ezetimibe (difference: -35.4%) and placebo (difference: -47.9%), with all results achieving strong statistical significance (P < 0.0001).

Beyond LDL-C, inclisiran also improved other lipid markers, including lipoprotein(a), and was well tolerated with no new safety issues.