The Medicines Company announced detailed results from ORION-10, the second of three pivotal 18-month low-density lipoprotein cholesterol (LDL-C) lowering Phase 3 clinical studies of inclisiran, an investigational twice-yearly therapy to reduce LDL-C and the first and only cholesterol-lowering treatment in the siRNA (small-interfering RNA) class. In ORION-10, twice-yearly dosing with inclisiran sodium 300 mg met all primary and secondary efficacy endpoints, was well-tolerated and again demonstrated an excellent safety profile. Full study results were presented during a late-breaking science session at the American Heart Association (AHA) Scientific Sessions in Philadelphia. For the primary endpoints of ORION-10, inclisiran delivered placebo-adjusted LDL-C reductions of 58% (p<0.0001) at day 510 and demonstrated time-averaged placebo-adjusted LDL-C reductions of 56% (p<0.0001) from days 90 through 540. The overall adverse event profiles of the placebo- and inclisiran-treated groups in ORION-10 were similar. A similar proportion of patients in the placebo and inclisiran groups experienced at least one serious treatment emergent adverse event (26.3% vs. 22.4%). The incidences of deaths (1.4% vs. 1.5%) and malignancies (3.3% vs. 3.3%) were also comparable between the placebo and inclisiran groups, respectively. Clinically significant elevations in liver function tests (ALT 0.3% vs. 0.3%, AST 0.6% vs. 0.5%) and serum creatinine increases (3.9% vs. 3.9%) were similar between the placebo and inclisiran groups, respectively. Clinically relevant adverse events at the injection site, predominantly mild and always transient, were reported in 0.9% of placebo-treated patients vs. 2.6% of inclisiran-treated patients.