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).
The effect of LEQVIO® on cardiovascular morbidity and mortality has not yet been determined.1
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 placebo (N=1,561)3
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
Adverse reactions at the injection site were the only common reported adverse reactions (LEQVIO® 8.2% vs placebo 1.8%). Hypersensitivity including anaphylactic reaction, angioedema, rash, urticaria and pruritus have been reported (frequency: not known)1
Please refer to the SmPC for full safety information, special warnings and precautions for use.
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
Deaths occurred in both treatment arms, with 1.5% (n=12) in LEQVIO® and 1.4% (n=11) in placebo.3
Learn more about the safety profile of LEQVIO®
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 the SmPC, adverse reactions at the injection site were the only common reported adverse reactions (LEQVIO® 8.2% vs placebo 1.8%). Hypersensitivity including anaphylactic reaction, angioedema, rash, urticaria and pruritus have been reported (frequency: not known)1
- In ORION-8 (N=3,274) 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
- Please refer to the SmPC for full safety information, special warnings and precautions for use.
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
V-CHALLENGE: Phase IV trial
- N=402; (396 patients completed the study [LEQVIO®: N=200; BPA: N=196])
- Male and female patients aged ≥18 years
- Patients with hypercholesterolemia or mixed dyslipidaemia at high or very high cardiovascular risk
- Elevated LDL-C levels (≥1.8 mmol/L) despite receiving a stable (≥4 weeks) MTD HI statin regimen with or without ezetimibe, and fasting triglycerides <4.5 mmol/L
- Participants on >1 other LLT on top of statin, or with a known statin intolerance, or receiving a PCSK9 mAb, or previous treatment with BPA (within 90 days) were excluded
- A 30-day screening period was followed by an open-label treatment period of 150 days, and a safety follow-up/end-of-study visit 30 days after the Day 150 visit
- In the open-label treatment period, eligible participants were randomised (1:1) to either LEQVIO® (inclisiran sodium 300 mg, equivalent to 284 mg inclisiran, administered at Day 1 and Day 90) or to BPA tablets 180 mg QD (until the day before the Day 150 visit)
- Participants were required to keep their background LLT unchanged during the study
- Randomisation was stratified by ezetimibe use
- The primary efficacy endpoint was the percentage change in LDL-C from baseline at Day 150
- The key secondary endpoint was percentage change in LDL-C from baseline to Day 150, stratified by background ezetimibe therapy
- Other secondary endpoints included:
- LDL-C goal attainment by participants at Day 150
- Absolute change from baseline of LDL-C level at Day 150
- Time-adjusted percentage change from baseline of LDL-C level after Day 30 and through Day 150
- Time-adjusted percentage change from baseline of LDL-C level between Day 90 and Day 150
- Prespecified exploratory endpoints included safety and tolerability data, such as treatment-emergent adverse events (TEAEs) and serious TEAEs
- In the SmPC, adverse reactions at the injection site were the only common reported adverse reactions (LEQVIO® 8.2% vs placebo 1.8%). Hypersensitivity including anaphylactic reaction, angioedema, rash, urticaria and pruritus have been reported (frequency: not known)1
- Overall in V-CHALLENGE, the adverse event profile of LEQVIO® was comparable with BPA and consistent with its established safety profile5,8
- The most common TEAEs during the on-treatment period included nasopharyngitis (10.3% vs 7.5%), hypertension (4.9% vs 4.5%), myalgia (3.4% vs 5.5%), back pain (3.4% vs 3.0%), urinary tract infection (3.0% vs 3.0%), headache (1.5% vs 3.5%) and blood creatine phosphokinase increased (1.5% vs 3.5%) with LEQVIO® vs BPA, respectively5
- Serious TEAEs were reported during the on-treatment period in 8.4% of participants receiving LEQVIO® (17 events) and 11.6% of those receiving BPA (23 events)5
- TEAEs leading to discontinuation were reported for 0 participants receiving LEQVIO® and 10 (5.0%) of those receiving BPA5
- Please refer to the SmPC for full safety information, special warnings and precautions for use
V-CHALLENGE was a randomised, controlled, open-label, parallel-group, multicentre Phase IV study comparing LEQVIO® with bempedoic acid (BPA) for LDL-C lowering and target attainment in adults with high or very high cardiovascular risk, on maximally tolerated high intensity statin ± ezetimibe.5
LEQVIO® provided sustained LDL-C reduction vs BPA‡‡§§5
A greater percentage reduction in LDL-C was observed with LEQVIO® vs BPA at Day 30, sustained until Day 150.¶¶5
Percentage change in LDL-C from baseline to Day 150 (primary endpoint)
Adapted from Hilgendorf I, et al. 2026.5
Mean baseline LDL-C: LEQVIO® 2.41±0.69 mmol/L; BPA 2.47±0.77 mmol/L.5
Data are presented as LSM percentage reduction from baseline.5
LEQVIO® showed greater percentage LDL-C reduction from baseline vs BPA regardless of background ezetimibe use§§5
In V-CHALLENGE, patients stratified by background ezetimibe use demonstrated greater percentage LDL-C reductions from baseline with LEQVIO® vs BPA at Day 150 (key secondary endpoint).5
Greater LDL-C reduction from baseline with LEQVIO® vs BPA at Day 150 with or without background ezetimibe5
Adapted from Hilgendorf I, et al. 2026.5
Mean baseline LDL-C: LEQVIO® 2.41±0.69 mmol/L; BPA 2.47±0.77 mmol/L.5
Greater LDL-C goal attainment observed with LEQVIO® vs BPA§§5
At Day 150, a higher proportion of patients treated with LEQVIO® achieved their individual LDL-C goals based on 2025 ESC guidelines vs patients treated with BPA.§§5
~4 times higher LDL-C goal attainment at Day 150 with LEQVIO® vs BPA (aOR=16.36; 95% CI: 9.72–27.54; p<0.0001; secondary endpoint, p-value descriptive only)‖‖5
Adapted from Hilgendorf I, et al. 2026.5
Individual LDL-C goals based on 2025 ESC guidelines: for high-risk patients <1.8 mmol/L, for very high-risk patients <1.4 mmol/L.5,6
Mean baseline LDL-C: LEQVIO® 2.41±0.69 mmol/L; BPA 2.47±0.77 mmol/L.5
‡‡In line with ESC 2025 guidelines (≥50% LDL-C reduction after an event).6
§§When used in combination with SOC (MTD HI statin±ezetimibe). Patients (N=402) were randomised (1:1) to receive either LEQVIO® (inclisiran sodium 300 mg, equivalent to 284 mg inclisiran, administered at Day 1 and Day 90) or to BPA tablets (180 mg once daily (QD) till the day before the Day 150 visit). The primary efficacy endpoint was the percentage change in LDL-C from baseline at Day 150. The key secondary endpoint was the percentage change in LDL-C from baseline to Day 150 with or without ezetimibe. Other secondary endpoints included individual responsiveness of participants at Day 150. Day 30 findings were based on an earlier study visit.5
¶¶The percentage change in LDL-C from baseline at Day 30 was analysed descriptively. The percentage change in LDL-C from baseline after Day 30 and through Day 150 is a secondary endpoint.5
‖‖Adjusted odds ratio (with two-sided p-value) obtained from logistic regression model with factors treatment, stratum and baseline LDL-C.5
A randomised, open-label, Phase IV study (NCT06431763) conducted in Germany, designed to demonstrate the superiority of LEQVIO® over BPA, when used in combination with standard of care (SOC) (MTD HI statin±ezetimibe), in reducing LDL-C levels at Day 150.5,7
Study population:5
Study design:5
Primary endpoint:5
Secondary endpoints:5
Safety assessments:5
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
aOR, adjusted odds ratio; ASCVD, atherosclerotic cardiovascular disease; BPA, bempedoic acid; CHD, coronary heart disease; CI, confidence interval; COVID-19, coronavirus disease 2019; CVD, cardiovascular disease; ESC, European Society of Cardiology; HDL, high-density lipoprotein; HeFH, heterozygous familial hypercholesterolaemia; HI, high-intensity; LDL-C, low-density lipoprotein cholesterol, LLT, lipid lowering therapy; LSM, least squares mean; mAb, monoclonal antibody; MTD, maximally tolerated dose; QD, once daily; PAD, peripheral artery disease; PCSK9, proprotein convertase subtilisin/kexin type 9; SD, standard deviation; SmPC, summary of product characteristics; SOC, standard of care; TEAE, treatment-emergent adverse event.
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.
Hilgendorf I, et al. Eur Heart J 2026; ehag738.
Mach F, et al. Eur Heart J 2025;46(42):4359–4378.
ClinicalTrials.gov. A study to investigate LDL-cholesterol lowering with inclisiran compared to bempedoic acid in patients with atherosclerotic cardiovascular disease. NCT06431763. Available at: https://clinicaltrials.gov/study/NCT06431763 [Accessed October 2026].
Wright RS, et al. J Am Coll Cardiol 2023;82:2251–2261.
LEQVIO® and the LEQVIO® logo are registered trademarks of Novartis AG. Licensed from Alnylam Pharmaceuticals, Inc.
UK | October 2026 | FA-11808380
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.
