High-risk and very high-risk patients meet LDL-cholesterol targets with lerodalcibep

The results of the LIBerate-HR study showed LDL-cholesterol reductions of 50–60% after 1 year of treatment with lerodalcibep. The dual treatment target of ≥50% decrease in LDL-cholesterol and reaching the adequate LDL-cholesterol goal was attained by 90% of participants on the novel PCSK9 inhibitor.

After encouraging phase 2 results, the third-generation PCSK9 inhibitor lerodalcibep advanced to phase 3 testing for long-term efficacy and safety [1]. The LIBerate-HR trial (NCT04806893) enrolled 922 adults with high to very high cardiovascular disease risk who were not reaching their LDL-cholesterol targets on oral lipid-lowering medication. The participants were randomised to lerodalcibep, 300 mg every 4 weeks (n=615), or a placebo (n=307). Efficacy endpoints were analysed in 3 population sets: per protocol (PP), modified intention-to-treat (mITT), and ITT with multiple imputation washouts, adjudicating discontinuing participants to an outcome similar to placebo.

On average, the participants were 65 years old and about 46% were women. “The entry level of LDL-cholesterol despite being on a maximum dose of statin and other oral lipid-lowering agents, was 116 mg/dL,” underlined Prof. Eric Klug (University of the Witwatersrand, South Africa).

The co-primary endpoints of percentage change at week 52 and mean of weeks 50 and 52 significantly favoured the study drug in all groups. Placebo-adjusted reduction rates at week 52 were -60.27% (PP), -56.19% (mITT), and -49.67% (ITT). The means of weeks 50/52 were -65.85%, -62.69%, and -55.33%, respectively. Furthermore, 90% of the active treatment cohort achieved their LDL-cholesterol goal together with a ≥50% decrease in LDL-cholesterol compared with 16% on placebo. Significant reductions were also determined for other lipids like non-HDL-cholesterol and apolipoprotein B. “Adverse events and key safety laboratory findings were similar in both arms,” noted Prof. Klug. An exception were injection site reactions with 6.9% (lerodalcibep) versus 0.3% (placebo).

“Lerodalcibep offers a novel, effective alternative to existing PCSK9 inhibitors,” Prof. Klug commented. He also pointed out that its long ambient stability allowed for patients’ home use.

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   1. Klug E. Randomised, double-blind, placebo-controlled, phase 3, study to evaluate lerodalcibep long-term efficacy and safety in patients with, or at very-high or high risk, for cardiovascular disease on stable lipid-lowering therapy. LB2, Session 405, ACC 2024 Scientific Session, 6–8 April, Atlanta, USA.

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Posted on 16 May 202413 June 2024