Inclisiran—New hope in the management of lipid disorders?

Dyrbuś, Krzysztof; Gąsior, Mariusz; Penson, Peter E.; Ray, Kausik K.; Banach, Maciej

doi:10.1016/j.jacl.2019.11.001

Cited by 97 publications

(99 citation statements)

References 59 publications

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“…Inclisiran sodium (inclisiran) is a short-chain, synthetic, small interfering ribonucleic acid (siRNA) that binds to PCSK9 messenger ribonucleic acid (mRNA) in hepatocytes, blocking PCSK9's translation and production [15]. Promising data from the ORION-1 phase II study, which demonstrated LDL-C lowering of > 50% with additional sustained pharmacodynamic effect and an ideal safety profile, led to the development of inclisiran's phase III ORION program [16,17].…”

Section: Inclisiran Molecule and Propertiesmentioning

confidence: 99%

A Critical Review of the Efficacy and Safety of Inclisiran

Hardy¹,

Niman²,

Pereira³

et al. 2021

Am J Cardiovasc Drugs

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The association between low-density cholesterol (LDL-C) and cardiovascular disease (CVD) is well-established, with an emphasis on lowering LDL-C levels to reduce cardiovascular events. Statin therapy has been the traditional treatment for LDL-C reduction, in addition to lifestyle modifications, but studies have shown that a substantial proportion of patients does not reach target LDL-C goals despite receiving maximally tolerated statin medications. Additionally, statin therapy is associated with a few shortcomings as many patients initiated on these medications discontinue treatment within 1 year because of lack of tolerability. Furthermore, guidelines from both the American College of Cardiology and the American Heart Association highlight the importance of obtaining LDL-C goals because of the residual atherosclerotic CVD risk that remains in high-risk populations. That the residual cardiovascular risk remains despite statin therapy highlights the importance of evaluating therapeutic approaches that possess effective lipid lowering that can be used adjunctively with statins. Much focus has been directed towards the proprotein convertase subtilisin/kexin type 9 (PCSK9) pathway, leading to the development of evolocumab and alirocumab, two human monoclonal antibodies directed against PCSK9. These agents have been shown to markedly decrease LDL-C levels and significantly reduce cardiovascular risk, but the need for biweekly or monthly subcutaneous injections has generated concerns for patient compliance. A new pathway is being studied in which a synthetic small interfering ribonucleic acid (siRNA) targets the PCSK9 gene expressed in hepatocytes to prevent PCSK9 production. The siRNA, inclisiran sodium, significantly reduces hepatic production of PCSK9, causing a marked reduction in LDL-C levels, and exhibits sustained pharmacodynamic effects when dosed subcutaneously every 6 months. This review presents and discusses the current clinical and scientific evidence pertaining to inclisiran sodium.

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Section: Inclisiran Molecule and Propertiesmentioning

confidence: 99%

A Critical Review of the Efficacy and Safety of Inclisiran

Hardy¹,

Niman²,

Pereira³

et al. 2021

Am J Cardiovasc Drugs

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“…Inclisiran (small interfering RNA molecule) acts with a completely new mechanism of inhibition of the PSCK9 protein in hepatocytes, targeting the messenger RNA for PCSK9 [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

Novel Therapeutical Approaches to Managing Atherosclerotic Risk

Giglio

Stoian

Al-Rasadi

et al. 2021

IJMS

Self Cite

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Atherosclerosis is a multifactorial vascular disease that leads to inflammation and stiffening of the arteries and decreases their elasticity due to the accumulation of calcium, small dense Low Density Lipoproteins (sdLDL), inflammatory cells, and fibrotic material. A review of studies pertaining to cardiometabolic risk factors, lipids alterations, hypolipidemic agents, nutraceuticals, hypoglycaemic drugs, atherosclerosis, endothelial dysfunction, and inflammation was performed. There are several therapeutic strategies including Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) inhibitors, inclisiran, bempedoic acid, Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RAs), and nutraceuticals that promise improvement in the atheromatous plaque from a molecular point of view, because have actions on the exposure of the LDL-Receptor (LDL-R), on endothelial dysfunction, activation of macrophages, on lipid oxidation, formations on foam cells, and deposition extracellular lipids. Atheroma plaque reduction both as a result of LDL-Cholesterol (LDL-C) intensive lowering and reducing inflammation and other residual risk factors is an integral part of the management of atherosclerotic disease, and the use of valid therapeutic alternatives appear to be appealing avenues to solving the problem.

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“…In recent years, with the advent of siRNA, researchers have designed a new generation of drugs to combat PCSK9 named Inclisiran. It can reduce the concentration of PCSK9 in the body by interfering PSCK9 gene expression in hepatocytes with a double-stranded short sequence of RNA, thereby reducing the degradation of LDLR and enhancing the ability of hepatocytes to eliminate LDL-C to reduce its levels ( Dyrbuś et al, 2020 ). In 2017, Ray et al (2017) found that Inclisiran could significantly reduce LDL-C after the first subcutaneous injection (>50%) and maintained this level for up to 1 year after the first injection.…”

Section: From Diagnosis Methods To Therapy Strategies Of Fh Based On mentioning

confidence: 99%

PCSK9 Variants in Familial Hypercholesterolemia: A Comprehensive Synopsis

2020

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Autosomal dominant familial hypercholesterolemia (FH) affects approximately 1/250, individuals and potentially leads to elevated blood cholesterol and a significantly increased risk of atherosclerosis. Along with improvements in detection and the increased early diagnosis and treatment, the serious burden of FH on families and society has become increasingly apparent. Since FH is strongly associated with proprotein convertase subtilisin/kexin type 9 ( PCSK9 ), increasing numbers of studies have focused on finding effective diagnostic and therapeutic methods based on PCSK9 . At present, as PCSK9 is one of the main pathogenic FH genes, its contribution to FH deserves more explorative research.

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Inclisiran—New hope in the management of lipid disorders?

Abstract: The version presented here may differ from the published version or from the version of the record. Please see the repository URL above for details on accessing the published version and note that access may require a subscription.

Cited by 97 publications

References 59 publications

A Critical Review of the Efficacy and Safety of Inclisiran

A Critical Review of the Efficacy and Safety of Inclisiran

Novel Therapeutical Approaches to Managing Atherosclerotic Risk

PCSK9 Variants in Familial Hypercholesterolemia: A Comprehensive Synopsis

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