Physicians' Academy for Cardiovascular Education

Small PCSK9 binding protein reduces LDL-c and is safe in patients with HeFH

News - Sep. 5, 2023

LIBerate-HeFH – Randomized, Double-Blind, Placebo-Controlled, Phase 3, Study to Evaluate the Long-Term Efficacy and Safety of Leroalcibep in Heterozygous Familial Hypercholesterolaemia Patients (LIBerate-HeFH)

Presented at the ESC congress 2023 by: Frederick Raal, MD - Johannesburg, South Africa

Introduction and methods

Lerodalcibep (LIB-003) is a small binding protein that binds to PCSK9. Binding to PCSK9 leads to blockage of the interaction between PCSK9 and the LDL receptor (LDLR), prevention of LDLR degradation, increased LDLR recycling, enhanced LDL-c clearance, and eventually lowered LDL-c levels. Lerodalcibep is an alternative to monoclonal antibodies against PCSK9. It consist of adnectin -a PCSK9-binding domain- fused with albumin to extend the plasma half-life to 12-15 days.

Smaller injection volumes are possible for lerodalcibep than for mAbs due to prolonged stability at ambient temperature, small size of the protein (77 kDa) and high solubility.

In the phase 3 LIBerate-HeFH trial, the safety and efficacy of lerodalcibep was evaluated in heterozygous FH (HeFH) patients on stable statin and/or ezetimibe therapy who required additional LDL-c lowering. 478 Patients with HeFH were randomized in a 2:1 ratio to monthly 1.2 ml SC injections of lerodalcibep 300 mg (n=319) or placebo (n=159) for 24 weeks.

The primary efficacy endpoints were the percent change from baseline in LDL-c at week 24 and then mean percent change of week 22 and week 24.

Main results


Addition of lerodalcibep 300 mg monthly to maximally tolerated lipid-lowering therapy reduced LDL-c further by 60% in patients with HeFH. Lerodalcibep was well tolerated and had a safety profile similar to placebo. Prof. Raal concluded: “These results support the use of lerodalcibep for the management of HeFH.”

- Our reporting is based on the information provided at the ESC Congress -

The results of the LIBerate-HeFH trial were simultaneously published in the Eur Heart J

Share this page with your colleagues and friends: