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

Study objective: This 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). Design: A systematic literature search was conducted in order to identify randomized controlled trials (RCTs) assessing the effect on lipoproteins and the safety profile of inclisiran. Results: Data 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 injectionsite 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 relevance: Inclisiran has favourable effects on serum lipid levels and an acceptable safety profile. Further well-designed RCTs are needed to explore its longer-term safety.