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Lerodalcibep (also known as LIB003) is an investigational drug being developed by LIB Therapeutics as a treatment for high cholesterol. It is a third-generation proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor designed to reduce low-density lipoprotein cholesterol (LDL-C), often referred to as "bad cholesterol."[1]
Mechanism of action
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Lerodalcibep is a small recombinant fusion protein known as an adnectin. It works by binding to the PCSK9 protein in the bloodstream. PCSK9's natural function is to destroy LDL receptors on the liver, which prevents the liver from clearing LDL-C from the blood. By inhibiting PCSK9, lerodalcibep prevents the degradation of these receptors, allowing them to remain active and more effectively remove LDL-C from circulation.
Clinical development and efficacy
[edit]Lerodalcibep has been studied in a comprehensive Phase 3 clinical program called the "LIBerate" program, which included over 2,900 patients with a range of conditions, including:[2]
- Atherosclerotic cardiovascular disease (ASCVD): In the LIBerate-HR trial, lerodalcibep significantly reduced LDL-C levels in patients with or at high risk for ASCVD who were already on stable statin therapy.[3]
- Heterozygous familial hypercholesterolemia (HeFH): In the LIBerate-HeFH trial, it was shown to significantly reduce LDL-C levels, with a mean reduction of 58.6% compared to a placebo.[4]
- Homozygous familial hypercholesterolemia (HoFH): Studies have demonstrated that lerodalcibep can be effective in this patient population, which has exceptionally high LDL-C levels and a heightened risk of premature cardiovascular disease.[citation needed]
The drug has consistently demonstrated the ability to achieve significant and sustained LDL-C reductions across its clinical trials. In addition to lowering LDL-C, it has also been shown to reduce other key lipid markers such as apolipoprotein B (ApoB) and lipoprotein(a) [Lp(a)].[citation needed]
Side effects and safety
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In clinical trials, lerodalcibep has been generally well-tolerated. The most common adverse event reported has been mild to moderate injection site reactions, such as redness, itching, or bruising. Overall, the safety profile has been similar to that of a placebo.
Regulatory status
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LIB Therapeutics has submitted a Biologics License Application (BLA) for lerodalcibep to the U.S. Food and Drug Administration (FDA) for the treatment of elevated LDL-C in patients with ASCVD or primary hyperlipidemia, including those with HeFH and HoFH. The FDA has accepted the application and set a Prescription Drug User Fee Act (PDUFA) target action date of December 12, 2025. The company also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA).
References
[edit]- ^ Ballantyne CM, Norata GD (September 2025). "The evolving landscape of targets for lipid lowering: from molecular mechanisms to translational implications". European Heart Journal. doi:10.1093/eurheartj/ehaf606. PMID 40911366.
- ^ "PH3 Liberate". www.libtherapeutics.com. Retrieved 12 November 2025.
- ^ Efficacy and Safety of Lerodalcibep in Patients With or at High Risk of Cardiovascular Disease - A Randomized Clinical Trial
- ^ Long-term efficacy and safety of lerodalcibep in heterozygous familial hypercholesterolaemia: the LIBerate-HeFH trial
