Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia

ABSTRACT

Introduction

Inclisiran is a novel posttranscriptional gene silencing therapy that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis by RNA interference and has a potent, dose-dependent, durable effect in lowering LDL-C, and therefore is an effective drug to treat dyslipidemia, reducing the risk for acute cardiovascular (CV) events. It is safe and well-tolerated.

Areas covered

This paper aims to review the mechanism of action of inclisiran while evaluating its efficacy and safety in the treatment of dyslipidemia from data of the clinical trials in the ORION program.

Expert opinion

Data from the clinical trials in the ORION program demonstrated efficacy and safety of inclisiran in patients with dyslipidemia. Adverse events were similar in the inclisiran and placebo groups in the clinical trials, although injection-site reactions were more frequent with inclisiran than with placebo. Although the combination of efficacy and safety makes inclisiran a good option for the treatment of dyslipidemia compared to other PCSK9 targeting therapeutic strategies, however, further studies should exclude the possibility that inclisiran, through lower-affinity interactions, may influence other mRNAs in the physiological milieu.

KEYWORDS:

• Atherosclerosis
• therapy
• inclisiran
• LDL
• PCSK9
• RNA

Funding

This paper was not funded.

Disclosure Statement

No potential conflict of interest was reported by the author(s).

Declaration of interests

The authors declare that the current research was conducted independently, in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. AP Stoian is currently Vice President of Romanian National Diabetes Committee, and she has given lectures, received honoraria and research support, and participated in conferences, advisory boards, and clinical trials sponsored by many pharmaceutical companies, including AstraZeneca, Boehringer Ingelheim, Medtronic, Eli Lilly, Merck, Novo Nordisk, Novartis, Roche Diagnostics, and Sanofi. A Janez discloses consultancies and speaker bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme (MSD), Novo Nordisk, Sanofi, and Medtronic. M. Rizzo is a full-time Professor of Internal Medicine at the University of Palermo, Italy, and currently the Medical Director, Novo Nordisk, in Eastern Europe; he has given lectures, received honoraria and research support, and participated in conferences, advisory boards, and clinical trials sponsored by many pharmaceutical companies including Amgen, Astra Zeneca, Boehringer Ingelheim, Kowa, Eli Lilly, Meda, Mylan, Merck Sharp & Dohme, Novo Nordisk, Novartis, Roche Diagnostics, Sanofi, and Servier. None of the above had any role in this article, which has been written independently, without any financial or professional help, and reflects only the opinion of the authors, without any role of the industry.