Lerodalcibep Delivers Significant LDL-C Reduction for High-Risk Cardiovascular Patients

Lerodalcibep (LIB003; LIB Therapeutics) demonstrated significant reductions of low-density lipoprotein cholesterol (LDL-C) in patients with cardiovascular disease (CVD) or who are at high-risk of CVD in the LIBERATE-HR trial (NCT04806893). The findings support the long-term use of lerodalcibep in patients who are unable to achieve adequate LDL-C reduction while receiving maximal tolerated statins alone.¹

The trial results support lerodalcibep as an effective monthly option for lowering LDL-C in patients with CVD or high CVD risk. Image Credit: © Anastasiia - stock.adobe.com

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality in North American and European countries and is projected to claim over 20 million lives annually in the coming years. Preventing ASCVD involves lifestyle changes such as diet, exercise, tobacco avoidance, and careful management of blood pressure and lipid levels, with LDL-C recognized as a major modifiable risk factor. Although statins and PCSK9 monoclonal antibodies are widely used, many patients still require more effective LDL-C lowering options.^2,3

Lerodalcibep is a novel, monthly subcutaneous anti-PCSK9 therapy, previously shown to significantly lower LDL-C in patients with or at risk for CVD. In the global, double-blind, placebo-controlled LIBERATE-HR trial, researchers evaluated the long-term safety and efficacy of lerodalcibep in 922 patients (mean age: 64.5 years; 44.9% female; baseline LDL-C: 116.2 mg/dL). Participants were randomized in a 2:1 ratio to receive either 300 mg of lerodalcibep or placebo for 52 weeks.³

The primary end points of the study were percent change from baseline and the mean of weeks 50 and 52, which were analyzed across 3 different study populations: modified intention-to-treat (mITT), intention-to-treat (ITT), and per-protocol (PP). Secondary end points included lipid apolipoprotein measures and achievement of guideline-recommended LDL-C targets.³

The mITT analysis showed that the least-squares (LS) mean differences between lerodalcibep and placebo were −56.19 (95% CI, −60.48 to −51.9) at week 52 and −62.69% (95% CI, −66.38 to −59.0) at the mean of weeks 50 and 52. In the ITT with washout imputation analysis, the LS mean change in LDL-C from baseline compared with placebo was −49.67% (95% CI, −53.47 to −44.97) at week 52 and had a mean of −55.33% (95% CI, −59.54 to −51.12). Lastly, there was an LS mean placebo-adjusted change in LDL-C from baseline of −60.27% (95% CI, −64.7 to −55.85) at week 52 and −65.85% (95% CI, −69.57 to −62.13) at the mean of weeks 50 and 52 with lerodalcibep.³

In the lerodalcibep group, 90% of patients achieved both a 50% or greater reduction in LDL-C and recommended LDL-C targets compared with the placebo group. Additionally, lerodalcibep treatment resulted in significant reductions to other atherogenic lipids and apolipoproteins including non-high density lipoprotein cholesterol (47.3%), very LDL-C (25.9%), apolipoprotein B (43%), lipoprotein(a) (30%), and triglycerides (14.1%). These decreases were consistent and independent of age, sex, body mass index, CVD status, or use of statin therapy.³

Lerodalcibep was well-tolerated, with treatment-emergent adverse events (TEAEs) comparable with the placebo groups. Mild or moderate injection site reactions were the most common TEAEs in the lerodalcibep group, affecting 6.9% of patients; however, these did not result in discontinuation of treatment.³

The trial results support lerodalcibep as an effective monthly option for lowering LDL-C in patients with CVD or high CVD risk. The findings show promise for patients who are unable to achieve adequate LDL-C reductions using other available agents, offering them a safe, efficacious, and convenient, once monthly alternative.

REFERENCES

1. Study of long-term efficacy and safety of lib003 in cvd or high risk for cvd patients needing further ldl-c reduction (liberate-hr). ClinicalTrials.gov Identifier: NCT04806893. Updated December 11, 2023. Accessed November 7, 2024. https://clinicaltrials.gov/study/NCT04806893?id=NCT04806893&rank=1

2. Investigators link early cholesterol exposure with faster atherosclerosis development. Pharmacy Times. September 13, 2024. Accessed November 7, 2024. https://www.pharmacytimes.com/view/investigators-link-early-cholesterol-exposure-with-faster-atherosclerosis-development

3. Klug E, Llerena S, Burgess L, et al. Efficacy and safety of lerodalcibep in patients with or at high risk of cardiovascular disease: a randomized clinical trial. JAMA Cardiol. July 3, 2024. doi:10.1001/jamacardio.2024.1659