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Review
. 2022 Nov 3;23(11):375.
doi: 10.31083/j.rcm2311375. eCollection 2022 Nov.

Inclisiran: A New Pharmacological Approach for Hypercholesterolemia

Stefania Angela Di Fusco  1 , Aldo Pietro Maggioni  2 , Chiara Bernelli  3 , Francesco Perone  4 , Vincenzo De Marzo  5 , Edoardo Conte  6 , Francesca Musella  7 , Giuseppe Uccello  8 , Leonardo De Luca  9 , Domenico Gabrielli  9 , Michele Massimo Gulizia  10 , Fabrizio Oliva  11 , Furio Colivicchi  1
Affiliations
Review

Inclisiran: A New Pharmacological Approach for Hypercholesterolemia

Stefania Angela Di Fusco et al. Rev Cardiovasc Med. .

Abstract

Therapeutic approaches based on gene silencing technologies represent a new opportunity to manage hypercholesterolemia. Inclisiran is a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA. Clinical studies have demonstrated that inclisiran is effective, safe, and well-tolerated in reducing low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia, atherosclerotic cardiovascular disease, and atherosclerotic cardiovascular disease risk equivalents. A meta-analysis of phase 3 trials demonstrated a 51% reduction in LDL-C levels at 18 months as compared with placebo. Adverse event incidence was found to be comparable in individuals treated with inclisiran and those receiving placebo, though the reactions at the site of injection were more common in patients receiving inclisiran as compared with those receiving placebo. The recommended inclisiran dose is 284 mg administered as a subcutaneous injection to be repeated after three months with a subsequent 6-month maintenance regimen. Overall, since the pharmacological efficacy of inclisiran in LDL-C reduction is comparable to that of monoclonal antibodies against PCSK9, the longer effect duration and the favorable safety profile may favor this newer approach for hypercholesterolemia management.

Keywords: LDL-cholesterol; cardiovascular disease; hypercholesterolemia; inclisiran; siRNA.

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Conflict of interest statement

The authors declare no conflict of interest. Leonardo De Luca is serving as one of the Editorial Board members and Guest Editors of this journal. Stefania Angela Di Fusco, Francesco Perone, Vincenzo De Marzo and Furio Colivicchi are serving as Guest Editors of this journal. We declare that they had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Brian Tomlinson.

Figures

Fig. 1.
Fig. 1.
Illustration of inclisiran effects on the liver cell. PCSK9 expressed by the liver mediates LDL-receptor degradation in lysosomes. Inclisiran is a small interfering RNA able to promote the degradation of the mRNA that encodes PCSK9, thereby it reduces PCSK9 availability and leads to an increased expression of LDL receptors. The result is an enhanced LDL-C clearance. ASGPR, asialoglycoprotein receptor; LDL-C, low-density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9; RISC, RNA-induced silencing complex; mRNA, messenger RNA.
See this image and copyright information in PMC

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