NEW CHOLESTEROL DRUG HAS NOVEL MECHANISM OF ACTION
May 3, 2022 - A cholesterol drug with a novel mechanism of action was recently approved. Inclisiran (Leqvio) is a small interfering ribonucleic acid (siRNA) that inhibits the production of PCSK9 in hepatocytes. PCSK9 is an enzyme that binds to LDL receptors on liver cells and causes them to degrade. LDL receptor loss reduces hepatocyte uptake of LDL and leads to higher LDL blood levels. (PCSK9 mechanism illustration) Two antibodies, alirocumab and evolocumab, are currently available that bind PCSK9 and inactivate it. Inclisiran blocks PCSK9 production at the mRNA level inside cells.
In one study (N=1561), inclisiran lowered LDL levels by 50% (baseline LDL 105 mg/dl) in patients on maximally tolerated statins who had atherosclerotic cardiovascular disease. In a similar study (N=482), patients with heterozygous familial hypercholesterolemia (baseline LDL 153 mg/dl) saw their LDL levels fall by 40% compared to an increase of 8% in placebo-treated patients. There is no information currently about its effects on clinical outcomes like heart attack and mortality.
Inclisiran is FDA-approved for patients with atherosclerotic cardiovascular disease and/or heterozygous familial hypercholesterolemia. It is given as a subcutaneous injection with dosing on day 1, 3 months later, and every 6 months thereafter. Besides mild injection site reactions, it has no significant side effects, and there are no known precautions, contraindications, or drug interactions. See Inclisiran (Leqvio) review for more.