Efficacy and safety of inclisiran a newly approved FDA drug: a systematic review and pooled analysis of available clinical studies

Abstract

Study objectiveThis systematic review and meta-analysis aimed to assess the efficacy and safety profile of treatment with inclisiran, a drug that has been recently approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA). DesignA systematic literature search was conducted in order to identify randomized controlled trials (RCTs) assessing the effect on lipoproteins and the safety profile of inclisiran. ResultsData were pooled from 5 RCTs, which included 4226 subjects. Meta-analyses of data suggested that the multiple-dose regimens of inclisiran yielded a significant reduction in serum levels of proprotein convertase subtilisin/kexin type 9 (MD = −78.23%, 95%CI: −86.74, −69.71) and low-density lipoprotein cholesterol (MD = −45.48%, 95%CI: −50.36%, −40.61%) throughout the studies. Furthermore, treatment with inclisiran significantly affected total cholesterol (MD = −13.67%, 95%CI: −20.78%, −6.57%), high-density lipoprotein cholesterol (MD = 8.29%, 95%CI: 4.66%,11.93%), non-HDL cholesterol (MD = −39.45%, 95%CI: −43.6%, −35.31%), apolipoprotein B (MD = −34.58%, 95%CI: −38.78%, −30.78%) and lipoprotein(a) (MD = −20.9%, 95%CI: −25.8%, −15.99%). Multiple-dose regimens of inclisiran were associated with increased risk of injection-site reactions (any reaction: OR = 5.86, 95%CI: 3.44, 9.98; mild reactions: OR = 5.19, 95%CI: 1.68, 16.07; moderate reactions: OR = 13.37, 95%CI: 3.17, 56.46), and bronchitis (OR = 1.58, 95%CI: 1.10, 2.26), while the incidence of the pre-specified exploratory CV endpoint significantly decreased at 18 months (OR = 0.74, 95%CI: 0.58, 0.94). Conclusion and relevanceInclisiran has favourable effects on serum lipid levels and an acceptable safety profile. Further well-designed RCTs are needed to explore its longer-term safety.