Inclisiran: the First Small Interfering RNA (SiRNA) for a Novel LDL-C Lowering Therapy in ASCVD

Abstract

Inclisiran is a small interfering RNA (siRNA). It inhibits the enzyme proprotein convertase subtilisin kexin type 9. By subcutaneous injection, it reduces serum low-density lipoprotein cholesterol (LDL-C). The US FDA and the Thai FDA approved incliseran to use in familial hypercholesterolemia (HeFH) or atherosclerotic cardiovascular disease (ASCVD) patients with 2 main conditions as (1) adjunctive treatment with statins when using high intensity statins in maximal tolerated dose but cannot achieve LDL-C target (2) single therapy in the case of statins intolerance or contraindication for statins. According to clinical trials, inclisiran significantly reduced LDL-C levels more than the placebo with mild adverse drug reactions. Moreover, inclisiran can sustain LDL-C reduction so it can be subcutaneously injected every 6 months. There is a benefit in patients with medication non-adherence, reducing their LDL-C level to prevent ASCVD. So, inclisiran is an alternative antihyperlipidemic agent for patients who want to control LDL-C levels. However, inclisiran is expensive. Thus, in the selection of drugs, it must be considered therapeutic efficacy, long-term safety and cost-effectiveness.