Lipid-efficacy RCT · JAMA Cardiol 2024
LIBerate-HR trial
Efficacy and Safety of Lerodalcibep in Patients With or at High Risk of Cardiovascular Disease: A Randomized Clinical Trial.
The bottom line
Monthly lerodalcibep added to maximally tolerated statins substantially lowers LDL-C and helps most high-risk patients reach guideline LDL-C targets, with a safety profile similar to placebo aside from mild/moderate injection site reactions.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Monthly 1.2-mL subcutaneous lerodalcibep, 300 mg
- Compared with
- Placebo
- People
- 922
- Who took part
- Individuals 18 years and older taking maximally tolerated statin therapy with LDL-C of 70 mg/dL or greater with CVD or 100 mg/dL or greater if at high risk of CVD
- Design
- randomized, double-blind, placebo-controlled phase 3 trial
- Follow-up
- 52 weeks
- Main question
- Percent change from baseline in LDL-C at week 52 and the mean of weeks 50 and 52 (co-primary end points)
Main result
The mean (SE) placebo-adjusted reduction in LDL-C with lerodalcibep by modified intention-to-treat (mITT) analysis was 56.2% (2.2%) at week 52 and 62.7% (1.9%) for the mean of weeks 50 and 52; 49.7% (2.4%) and 55.3% (2.2%) by ITT with imputation using a washout model, and 60.3% (2.3%) and 65.9% (1.9%) by per-protocol analysis at week 52 and the mean of weeks 50 and 52, respectively (P < .001 for all).
Effect on LDL cholesterol
Placebo-adjusted reduction in LDL-C: 56.2% (2.2%) at week 52 and 62.7% (1.9%) for mean of weeks 50 and 52 by mITT analysis (P < .001 for all)
Other results
With lerodalcibep, 555 of 615 participants (90%) achieved both a reduction in LDL-C of 50% or greater and recommended LDL-C targets during the study.
Safety
Treatment-emergent adverse events were similar between lerodalcibep and placebo, except for injection site reactions, which occurred in 42 of 613 participants receiving lerodalcibep (6.9%) compared to 1 of 307 receiving placebo (0.3%), were graded mild or moderate, and did not result in higher discontinuation of treatment, at 26 of 613 (4.2%) and 14 of 307 (4.6%), respectively. Sporadic in vitro antidrug antibodies were detected, which had no impact on free PCSK9 or LDL-C-lowering efficacy.
In the trial's own words
“The mean (SE) placebo-adjusted reduction in LDL-C with lerodalcibep by modified intention-to-treat (mITT) analysis was 56.2% (2.2%) at week 52 and 62.7% (1.9%) for the mean of weeks 50 and 52; 49.7% (2.4%) and 55.3% (2.2%) by ITT with imputation using a washout model, and 60.3% (2.3%) and 65.9% (1.9%) by per-protocol analysis at week 52 and the mean of weeks 50 and 52, respectively (P < .001 for all).”
Quoted from the abstract of JAMA Cardiol 2024, checked word for word against PubMed. PubMed 38958989 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Lerodalcibep (Lerochol)
Common questions
What did the LIBerate-HR trial find?
Monthly lerodalcibep added to maximally tolerated statins substantially lowers LDL-C and helps most high-risk patients reach guideline LDL-C targets, with a safety profile similar to placebo aside from mild/moderate injection site reactions.
Who was in LIBerate-HR?
922 people. Individuals 18 years and older taking maximally tolerated statin therapy with LDL-C of 70 mg/dL or greater with CVD or 100 mg/dL or greater if at high risk of CVD.
What was LIBerate-HR's main result?
The mean (SE) placebo-adjusted reduction in LDL-C with lerodalcibep by modified intention-to-treat (mITT) analysis was 56.2% (2.2%) at week 52 and 62.7% (1.9%) for the mean of weeks 50 and 52; 49.7% (2.4%) and 55.3% (2.2%) by ITT with imputation using a washout model, and 60.3% (2.3%) and 65.9% (1.9%) by per-protocol analysis at week 52 and the mean of weeks 50 and 52, respectively (P < .001 for all).
How much did LDL cholesterol change in LIBerate-HR?
Placebo-adjusted reduction in LDL-C: 56.2% (2.2%) at week 52 and 62.7% (1.9%) for mean of weeks 50 and 52 by mITT analysis (P < .001 for all)
Related trials
- LIBerate-HeFH (2023)In patients with heterozygous familial hypercholesterolaemia needing more LDL-C lowering, adding monthly subcutaneous lerodalcibep to therapy produced a large, highly significant LDL-C reduction versus placebo over 24 weeks with a safety profile similar to placebo aside from mild injection site reactions.
- MK-0616 phase 2b (2023)In this phase 2b trial, the oral PCSK9 inhibitor MK-0616 produced large, dose-dependent LDL-C reductions compared with placebo and was well tolerated over 8 weeks of treatment plus 8 weeks of follow-up.
- ORION-3 (2023)Twice-yearly inclisiran produced durable, substantial LDL cholesterol and PCSK9 lowering over 4 years of repeated hepatic dosing and was well tolerated with low rates of serious drug-related adverse events.
- PURSUIT (2025)In statin-treated patients with hypercholesterolemia, the oral PCSK9 inhibitor AZD0780 produced robust, dose-dependent LDL-C reductions over 12 weeks with an adverse event rate similar to placebo.
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