ORION-9 phase III trial of inclisiran meets primary endpoints in lowering LDL-C in HeFH patients.- The Medicines Co

The Medicines Company announced detailed results from ORION-9, the last of three pivotal 18-month low-density lipoprotein cholesterol (LDL-C) lowering Phase III 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-9, twice-yearly dosing (following initial and three-month doses) with inclisiran sodium 300 mg met all primary and secondary efficacy endpoints, was well-tolerated and demonstrated an excellent safety profile. For the primary endpoints of ORION-9, inclisiran delivered placebo-adjusted LDL-C reductions of 50% (71 mg/dL, p<0.0001) at day 510 in hefh patients and demonstrated time-averaged placebo-adjusted ldl-c reductions of 45 63 mg dl p><0.0001) from days 90 through 540.>

The overall adverse event profiles of the placebo- and inclisiran-treated groups in ORION-9 were similar. At least one serious treatment emergent adverse event was experienced by 13.8% of patients in the placebo-treated group and 7.5% of patients in the inclisiran-treated group. The incidences of deaths (0.4% vs. 0.4%) and malignancies (1.3% vs. 0.8%) were similar between the placebo and inclisiran groups, respectively. Low incidences of clinically significant elevations in liver function tests (ALT 0.4% vs. 1.2%, AST 0.4% vs. 0.8%) and serum creatinine increases (0.4% vs. 0.4%) were observed in the placebo and inclisiran groups, respectively, and none were considered related to study drug. Clinically relevant adverse events at the injection site, predominantly mild and always transient, were reported in 0.4% of placebo-treated patients vs. 13.7% of inclisiran-treated patients.

ORION-9 data will be submitted to a peer-reviewed medical journal. The company expects to file regulatory submissions in the U.S. in the fourth quarter of 2019 and in Europe in the first quarter of 2020. Full study results were presented during a late-breaking science session at the American Heart Association (AHA) Scientific Sessions.