Le médicament du mois. L’inclisiran (Leqvio®), hypocholestérolémiant puissant inhibant la synthèse de PCSK9 par la technique innovante de l’ARN interférent

editorial reviewed ; PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibition has proven its interest to potentiate the cholesterol-lowering effects of statins. Indeed, this protein contributes to the intracellular degradation of LDL cholesterol receptors and thereby reduces their recycling and expression at the hepatocyte membrane. PCSK9 inhibition allows a major and sustained reduction of LDL cholesterol (LDL-c) in patients with familial hypercholesterolaemia or with established cardiovascular disease. Two monoclonal antibodies that inhibit the effect of PCSK9 are currently commercialized, alirocumab and evolocumab. Another approach consists in the inhibition of PCSK9 synthesis. Inclisiran is a novel small interfering RNA-based therapy (anti-sense). By binding to the messenger RNA (mRNA) precursor of PCSK9, inclisiran inhibits the PCSK9 gene expression, resulting in increased hepatocyte recycling and membrane expression of LDL receptors and decreased levels of LDL-c. This article summarizes the mode of action, pharmacokinetics, efficacy, safety profile, indications and reimbursement conditions of inclisiran. This novel cholesterol-lowering drug is indicated as add-on therapy in adults with atherosclerotic cardiovascular disease or with heterozygous familial hypercholesterolaemia in whom LDL-c level is ? 100 mg/dl and does not reach target LDL-c levels despite statin and ezetimibe or without statin or ezetimibe in case of intolerance or contra-indication for one of these medications.