Inclisiran

(Leqvio®)

Leqvio®

Drug updated on 10/25/2024

Dosage FormInjection (subcutaneous; 284 mg/1.5 mL [189 mg/ml])
Drug ClassSmall interfering RNAs (siRNAs)
Ongoing and
Completed Studies
ClinicalTrials.gov

Indication

  • Indicated as an adjunct to diet and statin therapy for the treatment of adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce lowdensity lipoprotein cholesterol (LDL-C).

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Summary
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  • This summary is based on the review of 10 systematic review(s)/meta-analysis(es). [1-10]
  • Inclisiran significantly reduced LDL (Low-Density Lipoprotein)-C (MACE) levels by -45.48% (95% CI (95% CI: -51.75, -41.13, p<0.01): -50.36%, -40.61%) compared to placebo, with additional reductions in total cholesterol, non-HDL (MD = -39.45%, 95%CI: -43.6%, -35.31%) cholesterol, and apolipoprotein B levels. It also increased HDL-C levels significantly.
  • In patients with heterozygous familial hypercholesterolemia (HeFH), inclisiran reduced LDL-C by -48.62%, while in homozygous familial hypercholesterolemia (HoFH), the reduction was -9.12%, showing greater effectiveness in HeFH patients (P < 0.05).
  • Comparatively, inclisiran was slightly less effective than evolocumab, which reduced LDL-C by -61.09%, but it showed similar effectiveness to alirocumab (-46.35%).
  • Inclisiran demonstrated effectiveness in reducing major adverse cardiac events (MACE), with a significant reduction compared to placebo (RR (0.98,1.12) = 0.79, p = 0.05), making it beneficial for patients with cardiovascular disease.
  • Inclisiran was associated with a non-significant elevated risk of total adverse events (RR = 1.05, p = 0.16) and non-serious adverse events (RR = 1.09, p = 0.15) compared to placebo, while the risk of serious adverse events was lower (RR = 0.94, p = 0.67).
  • There was a significantly increased risk of injection-site reactions with inclisiran, including any reaction (OR (95% CI: 0.64, 0.81, p<0.01) = 5.86), mild reactions (OR = 5.19), and moderate reactions (OR = 13.37), while there was also an elevated risk of bronchitis (OR = 1.58).
  • Liver and kidney function tests, creatine kinase values, and platelet counts showed no significant differences between inclisiran and placebo.
  • Inclisiran significantly reduced LDL-C and other lipid parameters in patients with heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH), with a greater reduction in HeFH patients for LDL-C (-48.62% in HeFH vs. -9.12% in HoFH, P < 0.05). It also significantly reduced LDL-C in patients with atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk equivalents, showing consistent effectiveness across these populations.

Product Monograph / Prescribing Information

Document TitleYearSource
Leqvio (inclisiran) Prescribing Information.2024Novartis Pharmaceuticals Corporation, East Hanover, NJ

Systematic Reviews / Meta-Analyses

Document TitleYearSource
Efficacy of Inclisiran in Patients Having Familial Hypercholesterolemia: Heterozygous Compared to Homozygous Trait, a Systematic Review and Meta-analysis2024Critical Pathways in Cardiology
A systematic review and meta-analysis of tolerability, cardiac safety and efficacy of inclisiran for the therapy of hyperlipidemic patients2024Expert Opinion on Drug Safety
Proprotein convertase subtilisn/kexin type 9 inhibitors and small interfering RNA therapy for cardiovascular risk reduction: A systematic review and meta-analysis2023PloS One
Effectiveness and safety of Inclisiran in hyperlipidemia treatment: An overview of systematic reviews2023Medicine
Network Meta-Analysis of Randomized Trials Evaluating the Comparative Efficacy of Lipid-Lowering Therapies Added to Maximally Tolerated Statins for the Reduction of Low-Density Lipoprotein Cholesterol2022Journal of the American Heart Association
Cost-Effectiveness, Burden of Disease and Budget Impact of Inclisiran: Dynamic Cohort Modelling of a Real-World Population with Cardiovascular Disease2022PharmacoEconomics
The promising novel therapies for familial hypercholesterolemia2022Journal of Clinical Laboratory Analysis
PCSK9 inhibitors for secondary prevention in patients with cardiovascular diseases: a bayesian network meta-analysis2022Cardiovascular Diabetology
Efficacy and safety of inclisiran a newly approved FDA drug: a systematic review and pooled analysis of available clinical studies2022American Heart Journal Plus
Pooled Patient-Level Analysis of Inclisiran Trials in Patients With Familial Hypercholesterolemia or Atherosclerosis2021Journal of the American College of Cardiology

Clinical Practice Guidelines