Lerodalcibep: Another Crucial Addition to the Dyslipidaemia Arsenal

The recent comprehensive review in the Reviews in Cardiovascular Medicine highlights various therapeutic agents for dyslipidaemia [1], but notably, the inclusion of lerodalcibep is crucial, given its promising efficacy and safety profile. Lerodalcibep, a promising proprotein convertase subtilisin kexin-9 (PCSK9) adnectin, inhibits the binding of PCSK9 to low-density lipoprotein (LDL) receptors, preventing their degradation and consequently lowering LDL cholesterol (LDL-C) levels [2]. This mechanism is particularly beneficial for patients at high risk of atherosclerotic cardiovascular disease (ASCVD). In the 52-week LIBerate-HR trial, lerodalcibep demonstrated substantial efficacy in reducing LDL-C (60.3%) in patients with or at high-to-very high risk of ASCVD [2]. In the LIBerate-HeFH trial involving participants with heterozygous familial hypercholesterolemia, treatment with lerodalcibep for 24 weeks led to a substantial 58.6% reduction of LDL-C levels, with 68% of participants achieving an LDL-C reduction of at least 50% while meeting the European Society of Cardiology targets [3]. Importantly, the long-term LIBerate-OLE trial showed that monthly lerodalcibep administration reduced LDL-C by >60%, without any evidence of attenuation even after >2 years [4]. Lerodalcibep, administered subcutaneously, presents a comparable safety profile to placebo, which is essential for patient compliance and long-term care. Compared to monoclonal antibodies, the structure of lerodalcibep, which combines adnectin and human serum albumin, allows for smaller injection volumes, less frequent injections, and improved stability at room temperature. The legacy effect highlighted in the review underscores the need for sustained lipid-lowering therapy in preventing cardiovascular events. Consequently, integrating lerodalcibep into therapeutic options represent a significant enhancement to the treatment repertoire for attaining optimal cholesterol levels in patients who are statin-intolerant or need further LDL-C reduction.

References

[1] Li P, Jiang W. A New Insight on Atherosclerosis Mechanism and Lipid-Lowering Drugs. Reviews in Cardiovascular Medicine. 2025; 26: 25321. https://doi.org/10.31083/RCM25321.

[2] Klug EQ, Llerena S, Burgess LJ, Fourie N, Scott R, Vest J, et al. Efficacy and Safety of Lerodalcibep in Patients With or at High Risk of Cardiovascular Disease: A Randomized Clinical Trial. JAMA Cardiology. 2024; 9: 800–807. https://doi.org/10.1001/jamacardio.2024.1659.

[3] Raal F, Fourie N, Scott R, Blom D, De Vries Basson M, Kayikcioglu M, et al. Long-term efficacy and safety of lerodalcibep in heterozygous familial hypercholesterolaemia: the LIBerate-HeFH trial. European Heart Journal. 2023; 44: 4272–4280. https://doi.org/10.1093/eurheartj/ehad596.

[4] LIB Therapeutics. LIB Therapeutics Announce Positive Results from Lerodalcibep 72-Week Open-Label Extension Studies at American Heart Association 2024. 2024. Available at: https://cdn.prod.website-files.com/61e62faab82c326a4b4e92af/673bd0313462d3b1c033ef5e_2024%201118%20LIB%20AHA%202024%20PR.pdf (Accessed: 20 June 2025).