Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol

Two phase 3 randomized trials ORION-10 and ORION-11 evaluated inclisiran, a small interfering RNA (siRNA) therapeutic that inhibits hepatic PCSK9 synthesis, in patients with elevated LDL cholesterol despite maximally tolerated statin therapy. Inclisiran was administered subcutaneously on day 1, day 90, and every six months over 540 days. Compared with placebo, inclisiran reduced LDL cholesterol by 52.3% in ORION-10 and 49.9% in ORION-11 at day 510, with similar time-adjusted reductions over the study period. PCSK9 levels dropped 69.8% and 63.6% respectively. Adverse events were similar between groups, though injection-site reactions were more frequent with inclisiran and mostly mild. The data support inclisiran’s twice-yearly dosing schedule as a potent and well-tolerated cholesterol-lowering therapy.

Two phase 3 randomized trials ORION-10 and ORION-11 evaluated inclisiran, a small interfering RNA (siRNA) therapeutic that inhibits hepatic PCSK9 synthesis, in patients with elevated LDL cholesterol despite maximally tolerated statin therapy. Inclisiran was administered subcutaneously on day 1, day 90, and every six months over 540 days. Compared with placebo, inclisiran reduced LDL cholesterol by 52.3% in ORION-10 and 49.9% in ORION-11 at day 510, with similar time-adjusted reductions over the study period. PCSK9 levels dropped 69.8% and 63.6% respectively. Adverse events were similar between groups, though injection-site reactions were more frequent with inclisiran and mostly mild. The data support inclisiran’s twice-yearly dosing schedule as a potent and well-tolerated cholesterol-lowering therapy.