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Inc4.1

Inclisiran (Leqvio) Research

Mostly mechanism / observationalModerate safety

7 peer-reviewed studies

What the evidence says

Mostly mechanism / observational

Most Inclisiran (Leqvio) studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.

Most evidence is from medium-quality meta-analyses and randomised trials published 2017–2023 with a typical study size of 501 participants.

Based on 7 studies · 2 meta-analyses · 3 RCTs · 8,203 total participants

Confidence

High

By outcome

LDL cholesterol & lipids
Mostly mechanism / observational7 studies
Cardiovascular outcomes (pending)
Mostly mechanism / observational4 studies
Safety profile
Too few graded studies1 study

Steady research

2 studies in the last 5 years · Latest meta-analysis: 2021

20172023

1RCTn=3,178 · very large study2020

Inclisiran administered subcutaneously on day 1, day 90, and every 6 months reduced LDL cholesterol by approximately 50%.

Ray, Wright, Kallend, Koenig, Leiter, Raal, Bisch, Richardson, Jaros, Wijngaard, Kastelein · The New England journal of medicine (2020)

ORION-10 and ORION-11 randomized, placebo-controlled phase 3 trials in atherosclerotic cardiovascular disease / high risk
Placebo-corrected LDL-C reductions of roughly 50%, sustained across the dosing interval
Dosed on day 1, day 90, then every 6 months — establishing the twice-yearly maintenance schedule

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2RCTn=482 · medium study2020

Inclisiran reduced LDL cholesterol levels in patients with heterozygous familial hypercholesterolemia.

Raal, Kallend, Ray, Turner, Koenig, Wright, Wijngaard, Curcio, Jaros, Leiter, Kastelein · The New England journal of medicine (2020)

ORION-9 randomized, placebo-controlled phase 3 trial in heterozygous familial hypercholesterolemia
Placebo-corrected LDL-C reduction of about 48% with twice-yearly maintenance dosing
Confirms efficacy in a high-LDL genetic population on top of statins

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3RCTn=501 · large study2017

A small interfering RNA targeting PCSK9 messenger RNA produced sustained reductions in LDL cholesterol.

Ray, Landmesser, Leiter, Kallend, Dufour, Karakas, Hall, Troquay, Turner, Visseren, Wijngaard, Wright, Kastelein · The New England journal of medicine (2017)

ORION-1 phase 2, double-blind, placebo-controlled, multiple-ascending-dose trial
Established the siRNA mechanism and the day-1/day-90 two-dose regimen in patients
Sustained LDL-C lowering through day 180–240 after dosing

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4Meta-Analysisn=3,660 · very large study2021

Across the phase 3 program, inclisiran consistently lowered LDL cholesterol by approximately half with a favorable safety profile.

Wright, Ray, Raal, Kallend, Jaros, Koenig, Leiter, Landmesser, Schwartz, Friedman, Wijngaard, Garcia Conde, Kastelein · Journal of the American College of Cardiology (2021)

Pooled patient-level analysis across ORION-9, ORION-10, and ORION-11 (n≈3,660)
Consistent ~50% LDL-C reduction across populations and subgroups
Injection-site reactions more frequent than placebo but mostly mild and transient

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5Open-Labeln=382 · medium study2023

Inclisiran provided durable LDL-cholesterol reduction over four years of open-label dosing with an acceptable safety profile.

Ray, Troquay, Visseren, Leiter, Scott Wright, Vikarunnessa, Talloczy, Zang, Maheux, Lesogor, Landmesser · The lancet. Diabetes & endocrinology (2023)

ORION-3: 4-year open-label extension of ORION-1
LDL-C reduction of roughly 45% sustained across repeated twice-yearly dosing
No new safety signals over long-term follow-up; injection-site reactions remained the main adverse effect

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6Meta-Analysis2020

Inclisiran significantly reduced LDL cholesterol compared with placebo across randomized trials.

Khan, Naz, Qamar Masood, Shah · The American journal of cardiology (2020)

Meta-analysis of randomized inclisiran trials in hypercholesterolemia
Significant LDL-C reduction versus placebo, consistent with the ~50% trial estimates
Adverse events broadly comparable to placebo aside from injection-site reactions

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7Review2020

Inclisiran uses GalNAc-conjugated RNA interference to silence hepatic PCSK9, enabling infrequent subcutaneous dosing.

German, Shapiro · BioDrugs (2020)

Mechanistic review of inclisiran's GalNAc-conjugated siRNA approach to PCSK9
Explains hepatocyte-targeted RNA interference and the resulting long duration of action
Contrasts the siRNA strategy with statins and PCSK9 monoclonal antibodies

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View in Research Library

Inclisiran (Leqvio) Research

Mostly mechanism / observational

Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol.

Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia.

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol.

Pooled Patient-Level Analysis of Inclisiran Trials in Patients With Familial Hypercholesterolemia or Atherosclerosis.

Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial.

Meta-Analysis of Inclisiran for the Treatment of Hypercholesterolemia.

Small Interfering RNA Therapeutic Inclisiran: A New Approach to Targeting PCSK9.