New PCSK9 inhibitor achieves LDL-C goals in high-risk and very high-risk patients

Depending on the analysed population, lerodalcibep reduced low-density lipoprotein-cholesterol (LDL-C) of 50–60% at week 52 of the phase 3 LIBerate-HR trial. The dual treatment target of ≥50% decrease in LDL-C and reaching the adequate LCL-C goal was attained by 90% on the study drug.

The phase 3 LIBerate-HR trial (NCT04806893) enrolled adults with high to very high cardiovascular disease risk not reaching their LDL-C targets on oral lipid-lowering medication [1]. The 922 participants were randomised to the 3^rd generation PCSK9 inhibitor lerodalcibep (300 mg every 4 weeks) or placebo. 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%, -55.33%, respectively. Furthermore, 90% of the active treatment cohort achieved their LDL-C goal together with a ≥50% decrease in LDL-C compared with 16% on placebo. Significant declines were also determined for other lipids like non-HDL-C and apolipoprotein B.

“Adverse events and key safety laboratory findings were similar in both arms,” notified 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, further pointing out that its long ambient stability allowed for patient’s 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.

Medical writing support was provided by Karin Drooff, MPH.
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Posted on 10 April, 202411 April, 2024