The ORION-10 trial revealed 300 mg inclisiran twice-yearly reduced LDL-C levels by 58% in patients with atherosclerotic cardiovascular disease.
R. Scott Wright, MD
Results of the phase 3 ORION-10 study examining the effects of inclisiran on elevated LDL-C in patients with atherosclerotic cardiovascular disease(ASCVD) has returned positive results, indicating inclisiran could reduce LDL-C by 58% compared with placebo.
Presented at the American Heart Association (AHA) 2019 Scientific Sessions in Philadelphia, results of the phase 3 trial indicate a new treatment for elevated cholesterol could be on the horizon in the form of the only cholesterol-lowering therapy in the small-interfering RNA class.
With a substantial number of patients with ASCVD failing to achieve LDL-C goals with the use of statin therapy, investigators conducted the ORION program to evaluate inclisiran—in twice-yearly dosing—use as a cholesterol-lowering therapy. The phase 3, placebo-controlled, double-blind, randomized trial included 1561 adults patients with stable ACSVD with LDL-C at a level of 70 mg/dL or greater despite maximum tolerated oral statin therapies from 145 sites.
Patients included in the study were randomized in a 1:1 ratio to receive inclisiran 300 mg twice-yearly or placebo therapy over the course of 18 months. Injections were given on day 1, day 90, and every 6 months after. The primary endpoints were percent change versus placebo at day 510 and time-adjusted average percentage change from baseline between day 90 up to day 540. Secondary endpoints included LDL-C change over time and changes in PSCK9 and other lipids.
Upon analyses, investigators noted the study achieved both primary endpoints—specifically, patients receiving inclisiran experienced LDL-C reductions of 58% at day 510 and demonstrated a time-averaged placebo-adjusted reduction of 56% from day 90 through day 540.
In regard to safety, investigators noted inclisiran patients experienced similar rates of adverse events as patients in the placebo arm. Investigators did note an increase in injection sites adverse events compared to placebo (2.6% versus 0.9%, respectively), but investigators pointed out none of these events were severe or persistent.
This study, “Safety and Efficacy of Inclisiran in Patients With ASCVD and Elevated LDL Cholesterol-Results From the Phase 3 ORION-10 Trial,” was presented by R. Scott Wright at AHA 2019.