Experimental PCSK9 Inhibitor Substantially Reduces LDL Cholesterol

The ORION-1 clinical trial demonstrated that inclisiran was able to effectively reduce LDL cholesterol levels compared with placebo, according to a presentation at the 2017 American College of Cardiology Annual Scientific Session.

Inclisiran is a drug that targets PCSK9 messenger RNA. The goal of the trial was to determine whether the new drug could reduce LDL cholesterol levels among patients with cardiovascular risks.

Included in the study were 501 patients age 18 or older with LDL cholesterol more than 70 mg/dl for patients with history of atherosclerotic cardiovascular disease or more than 100 mg/dl for patients without history of the condition, according to the presentation. Patients included were also treated with the highest dose or statin with or without other drugs for at least 30 days.

Patients were randomized to receive a subcutaneous injection of inclisiran or placebo, and assigned to 1 of 8 cohorts: a single dose of inclisiran 200-mg, 300-mg, 500-mg, or placebo on day 1, or 2 doses of inclisiran 100-mg, 200-mg, 300-mg, or placebo on days 1 and 90, according to the study.

A single treatment with inclisiran 200-mg was observed to reduce LDL cholesterol by 27.9% at 180 days. The investigators also discovered that a single dose of 300-mg and 500-mg inclisiran reduced LDL by 38.4% and 41.9%, respectively. The researchers said that a single dose of placebo was observed to raise LDL levels by 2.1%.

The results were most significant among the double dose cohort, with a double dose of 300-mg inclisiran dropping LDL cholesterol levels by 52.6%. A double dose of 100-mg inclisiran reduced LDL levels by 35.5%, and a double dose of 200-mg the drug reduced levels by 44.9%. However, a double dose of placebo increased LDL cholesterol levels by 1.8%.

The authors found that 11% of patients in the inclisiran cohorts experienced serious adverse events, while only 8% of placebo patients experienced serious adverse events.

The researchers reported that among patients with high cardiovascular risk, inclisiran effectively reduced LDL cholesterol levels compared with placebo. Overall, patients treated with a double dose of 300-mg inclisiran benefited from the greatest reduction in cholesterol.

The investigators concluded that these findings should lead to additional clinical trials to assess inclisiran in patients with cardiovascular risks.