Two single injections of inclisiran, a small interfering RNA (siRNA) that targets PCSK9 mRNA, induce a 50% reduction in LDL-cholesterol (LDL-C) levels in 6 months, according to findings from the phase II ORION-1 trial presented at ACC.17. A total of 501 patients at high risk of cardiovascular disease and with high LDL-C levels were randomly assigned to receive one or two injections (at days 1 and 90) of inclisiran at three different doses or placebo. All inclisiran regimens induced a significant reduction in LDL-C levels at 180 days, but two injections of 300 mg inclisiran produced the greatest effect, with mean reductions from baseline of 69.1% in PCSK9 levels and 52.6% in LDL-C levels (P <0.001). PCSK9 and LDL-C levels remained lower than baseline at day 240 with all doses of inclisiran.