Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia

This phase 3, double blind, randomized trial evaluated the efficacy and safety of inclisiran, a small interfering RNA targeting PCSK9 synthesis, in adults with heterozygous familial hypercholesterolemia. Participants received subcutaneous inclisiran (300 mg) or placebo on days 1, 90, 270, and 450. The primary endpoints were the percent change in LDL cholesterol levels at day 510 and the time-adjusted percent change from baseline between days 90 and 540. Results showed a 39.7% reduction in LDL cholesterol with inclisiran versus an 8.2% increase with placebo (between group difference: 47.9 percentage points, P<0.001). Time averaged reductions were similarly significant (−38.1% vs. +6.2%). Adverse events were comparable between groups, with injection site reactions more frequent in the inclisiran group. The study concluded that inclisiran significantly lowers LDL cholesterol with a twice-yearly dosing regimen and an acceptable safety profile.

This phase 3, double blind, randomized trial evaluated the efficacy and safety of inclisiran, a small interfering RNA targeting PCSK9 synthesis, in adults with heterozygous familial hypercholesterolemia. Participants received subcutaneous inclisiran (300 mg) or placebo on days 1, 90, 270, and 450. The primary endpoints were the percent change in LDL cholesterol levels at day 510 and the time-adjusted percent change from baseline between days 90 and 540. Results showed a 39.7% reduction in LDL cholesterol with inclisiran versus an 8.2% increase with placebo (between group difference: 47.9 percentage points, P<0.001). Time averaged reductions were similarly significant (−38.1% vs. +6.2%). Adverse events were comparable between groups, with injection site reactions more frequent in the inclisiran group. The study concluded that inclisiran significantly lowers LDL cholesterol with a twice-yearly dosing regimen and an acceptable safety profile.