Prescribing information (external link)
LEQVIO® (inclisiran) is indicated in adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia, as an adjunct to diet:1
in combination with a statin or statin with other lipid-lowering therapies in patients unable to reach low-density lipoprotein cholesterol (LDL-C) goals with the maximum tolerated dose of a statin, or
alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated
For full safety information, please refer to the LEQVIO® Summary of Product Characteristics (SmPC).
LEQVIO® efficacy
LEQVIO® lowers LDL-C by ~50% from baseline in as little as 3 months and maintains it between 6-monthly injections (after initial and loading doses) in patients on a maximally tolerated statin*2,3
The efficacy and safety profile of LEQVIO® was characterised in ORION-10 and ORION-11, randomised, double-blind, placebo-controlled trials in patients with atherosclerotic cardiovascular disease (ASCVD, or ASCVD risk equivalents)† and the ORION-8 open-label extension.2–4
ORION-10: Pivotal trial
Baseline LDL-C levels 2.70±1.02 mmol/L with LEQVIO® and 2.71±0.96 mmol/L with placebo
LDL-C reductions were achieved on top of a maximally tolerated statin and/or other LLT
The placebo-corrected percentage change in LDL cholesterol level from baseline to Day 510
The time-adjusted percentage change in LDL cholesterol level from baseline after Day 90 and up to Day 540
The absolute change in LDL cholesterol level from baseline to Day 510
The time-adjusted absolute change in LDL cholesterol level from baseline after Day 90 and up to Day 540
The percentage change from baseline to Day 510 in levels of PCSK9, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (HDL) cholesterol
≥1.8 mmol/L (≥70 mg/dL) for patients with ASCVD
Intolerance to any dose of any statin must be documented in their medical history
Patients not receiving a statin must have documented evidence of intolerance to all doses of at least two different statins
The majority of these reactions were mild, with none being severe or persistent
Discontinuation rates due to adverse events were balanced among both treatment groups: 2.4% (n=19) vs 2.2.% (n=17) of patients treated with LEQVIO® and placebo, respectively
With respect to liver and kidney function, levels of creatine kinase and high-sensitivity C-reactive protein, and platelet count were also similar in the LEQVIO® and placebo groups
Higher percentage change from baseline in LDL-C with LEQVIO® vs placebo3
Effective LDL-C reduction
Mean difference vs placebo from baseline at Month 17 (95% CI: −55.7 to −48.8; p<0.001, coprimary endpoint)
Sustained LDL-C reduction
Time adjusted, placebo-corrected percentage change from baseline after Month 3 up to Month 18 (95% CI: −56.2 to −51.3; p<0.001, coprimary endpoint)
Adapted from Ray KK, et al 2020.3
ORION-10 (N=1561) was a multicentre, double-blind, randomised, placebo-controlled 18-month clinical trial. Patients were randomised (1:1) to receive subcutaneous injections of LEQVIO® (284 mg) or matching placebo on top of a maximally tolerated statin and/or other lipid-lowering therapy.3
Primary endpoints in ORION-10:3
Key secondary endpoints in ORION-10:3
Full details of other prespecified secondary endpoints are listed in the supplementary appendix.
ORION-10 | |
Number of patients | N=1561 |
Where | USA |
Patient population | Adults with ASCVD (CHD, CVD, PAD) |
Patient eligibility criteria:‡3
LDL-C at screening:
Patients on statins should be receiving a maximally tolerated dose:
‡List of eligibility criteria is not exhaustive.
LEQVIO® 284 mg (or placebo) was administered subcutaneously by a healthcare professional initially, again at Month 3, and then every 6 months over a period of 18 months.3
Additional follow-up visits took place in Months 1, 5, 11 and 17.3
Adverse events and clinical laboratory values were recorded at all visits through the end-of-trial visit (Month 18).3
LEQVIO® has a safety profile generally comparable to placebo, with injection-site reactions being the only reported adverse event (8.2% vs placebo 1.8%, in the pivotal studies)1–3
Injection-site adverse reactions were more frequent with LEQVIO® than placebo: 2.6% (n=20) vs 0.9% (n=7), respectively.3
Laboratory results were similar in the LEQVIO® and placebo groups.3
The safety profile for LEQVIO® has been well characterised
ORION-8: Long-term extension
Baseline LDL-C level: 2.9±1.2 mmol/L
Results seen in combination with a maximally tolerated statin
Proportion of patients achieving pre-specified LDL-C goals at the end of the study (either Day 1080 or ≥90 days following the last dose of LEQVIO®)
Pre-specified lipid goals: ASCVD <1.8 mmol/L; ASCVD risk equivalent <2.6 mmol/L
Safety profile
Percent and absolute change in LDL-C from baseline to end of study
In ORION-8 (N=3,274), the safety profile of LEQVIO® remained consistent with previous reports, with no new safety signals4
The most common treatment-emergent adverse events were COVID-19 (13.8%), diabetes mellitus inadequate control (7.0%) and hypertension (7.0%)4
The most common treatment-emergent serious adverse events were coronary artery disease (2.0%), COVID-19 (1.5%) and acute myocardial infarction (1.3%)4
Sustained LDL-C reduction and target achievement4
(n=2731)
achieved pre-specified LDL-C goals by end of study
Pre-specified lipid goals: ASCVD <1.8 mmol/L; ASCVD risk equivalent <2.6 mmol/L
(n=2731)
mean percent change in LDL-C from baseline at end of study
§Includes subjects from ORION-9/10/11 who completed the study at Day 1080 and those who completed the study 90 days after their last dose.4
ORION-8 was an open-label extension of the preceding Phase II and III placebo-controlled and open-label extension trials. Following completion of the parent trial, patients received open-label LEQVIO® twice yearly (after initial and 3-month doses) until Day 990, followed by an end-of-study visit at Day 1080 or ≥90 days after the last dose.4
Primary endpoints in ORION-8:4
Key secondary endpoints in ORION-8:4
Patient eligibility:
Adult patients with heterozygous familial hypercholesterolaemia (HeFH), ASCVD or ASCVD risk equivalent conditions, who completed one of the parent trials (ORION-3, ORION-9, ORION-10 or ORION-11) with no intent to alter the background LLTs used during the parent trial and were willing and able to give informed consent.4
¶The ORION-3 trial was an open-label extension of the Phase II ORION-1 trial.4
‖One LEQVIO® participant in ORION-9/10/11 did not receive any injection in ORION-8.4
**Reasons for not completing the 3 years of treatment included: sponsor’s administrative decision for the roll-over ORION-3 participants only (8.3%), death (5.0%), withdrawal of consent (4.8%), lost to follow-up mostly during the COVID-19 pandemic period (3.1%), other (2.3%) and adverse events (1.4%).4
Adapted from Wright RS, 2024.4
††Participants from ORION-3 did not receive any drug administration on Day 1. Only participants on placebo in feeder trials received an active LEQVIO® injection at Day 1; participants who received LEQVIO® in those trials received blinded placebo at this visit.4
No new safety signals
Resource
LEQVIO®: A practical guide
Your Guide to LEQVIO®
A quick-guide to LEQVIO®, with information on NICE guidance and the NHS commercial agreement through to dosing and administration.
*In ORION-10, the baseline mean (±SD) LDL-C levels were 2.70±1.02 mmol/L with LEQVIO® and 2.71±0.96 mmol/L with placebo. At Month 17, LEQVIO® delivered placebo-corrected LDL-C reductions of 52.3%, as compared with baseline (−51.3% with LEQVIO® vs +1.0% with placebo; 95% CI: –55.7 to −48.8; p<0.001; co-primary endpoint), with a time-adjusted LDL-C reduction of 53.8% (−51.3% with LEQVIO® vs +2.5% with placebo; 95% CI: −56.2 to −51.3; p<0.001) from baseline between Months 3 and 18 relative to placebo (co-primary endpoint).3
†ASCVD risk equivalents included type 2 diabetes, HeFH or a 10-year risk of a cardiovascular event of ≥20% as assessed by the Framingham Risk Score for Cardiovascular Disease or equivalent.3
ASCVD, atherosclerotic cardiovascular disease; CHD, coronary heart disease; CI, confidence interval; COVID-19, coronavirus disease 2019; CVD, cardiovascular disease; HDL, high-density lipoprotein; HeFH, heterozygous familial hypercholesterolaemia; LDL-C, low-density lipoprotein cholesterol, LLT, lipid lowering therapy; PAD, peripheral artery disease; PCSK9, proprotein convertase subtilisin/kexin type 9; SD, standard deviation; SmPC, summary of product characteristics.
References
LEQVIO® Summary of Product Characteristics.
Landmesser U, et al. Eur Heart J 2025:ehaf68.
Ray KK, et al. N Engl J Med 2020;382:1507–1519 and supplementary data.
Wright RS, et al. Cardiovasc Res 2024;120:1400–1410.
LEQVIO® and the LEQVIO® logo are registered trademarks of Novartis AG. Licensed from Alnylam Pharmaceuticals, Inc.
UK | April 2026 | FA-11570713
Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis online through the pharmacovigilance intake (PVI) tool at www.novartis.com/report, or alternatively email [email protected] or call 01276 698370.
