CHSU Discovery

OBJECTIVE

To review the current pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of inclisiran in lowering lipid levels.

DATA SOURCES

A PubMed (from December 1, 2014 to April 15, 2022) and ClinicalTrials.gov search was conducted using ALN-PCSsc, ALN-60212, PCSK9si KJX-839, and inclisiran. Additional articles were identified by hand from references.

STUDY SELECTION AND DATA EXTRACTION

We included English-language articles evaluating inclisiran pharmacology, efficacy, or safety in humans for lowering low-density lipoprotein cholesterol (LDL-C).

DATA SYNTHESIS

Inclisiran is a novel small interfering RNA-based therapy administered as a twice-yearly subcutaneous injection. By binding to the messenger RNA (mRNA) precursor of proprotein convertase subtilisin/kexin type 9 (PCSK9), inclisiran inhibits expression of the PCSK9 gene, resulting in increased recycling and expression of LDL receptors and decreased levels of LDL-C. Like PCSK9 inhibitors, inclisiran was associated with a comparable extent of LDL-C reduction in several phase II/III trials. Compared with placebo, inclisiran was found to have similar adverse events except for injection-site reaction.

RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE

Currently, inclisiran lacks data on clinical outcome improvement or long-term safety. However, it may play a role in patients with atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalent if optimal LDL-C cannot be achieved by statins and PCSK9 inhibitors cannot be tolerated. The drug may be used for heterozygous familial hypercholesterolemia.

CONCLUSION

Inclisiran is an effective and safe medication for lowering LDL-C levels. Additional data regarding efficacy on cardiovascular outcomes and long-term safety profile with inclisiran are needed.