Update on Inclisiran for Treatment of Hypercholesterolemia

Abstract

Background: Inclisiran is a drug under development that inhibits the hepatic synthesis of proprotein convertase subtilis tin/Kexin type 9 (PCSK9) leading to reduction in plasma levels of low-density lipoprotein-cholesterol (LDL-C).

Methods: Review of pertinent English literature by Pubmed search until June 12, 2020. Search terms are lipids, PCSK9, LDL-C, inclisiran, safety, efficacy.Studies included are randomized trials, meta-analyses, and review articles.

Results: Inclisiran is administered by subcutaneous (SC) injection at day 1, day 90, then every 6 months. In patients with atherosclerotic cardiovascular (CV) disease and those with heterozygous familial hypercholesterolemia receiving maximally tolerated statins, the placebo-adjusted percent reduction in LDL-C levels was 48% to 52% after 6 months. Inclisiran also lowers other atherogenic lipoproteins such non-high-density lipoprotein-cholesterol (nonHDL-C) by 43 to 47%, apoprotein B (apo B) 39% to 43%, lipoprotein(a) by 18-25% compared with placebo. Efficacy of inclisiran in lowering LDL-C levels was similar in patients with and without diabetes, and patients with normal renal function compared with those with severe renal impairment. Inclisiran is overall well-tolerated. Most common adverse effects are injection site reactions.

Conclusions: Inclisiran is an effective and long-acting drug for lowering LDL-C levels. Studies are underway to evaluate effects of inclisiran on CV events and mortality.