Lerodalcibep-liga as an Injectable Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9)-Targeted Therapy for Patients With Hypercholesterolemia.
TL;DR
Lerodalcibep-liga is an additional potent injectable PCSK9-directed treatment for adults requiring substantial LDL-C reduction, including those with HeFH, however, alirocumab or evolocumab may remain preferable when demonstrated cardiovascular event reduction is a major consideration in treatment selection.
Abstract
Objective
To critically review the pharmacology, clinical efficacy, safety, and potential therapeutic role of lerodalcibep-liga within the expanding landscape of proprotein convertase subtilisin/kexin type 9 (PCSK9)-directed therapies for patients with hypercholesterolemia. DATA SOURCES PubMed, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched through August 2026. STUDY SELECTION AND DATA EXTRACTION Clinical trials evaluating lerodalcibep-liga in patients with hypercholesterolemia were included. Full-text peer-reviewed publications underwent detailed evaluation; conference abstracts and posters were summarized descriptively. The search identified one phase 1 study, two phase 2 trials, and six phase 3 trials. DATA SYNTHESIS Monthly subcutaneous lerodalcibep-liga produced low-density lipoprotein cholesterol (LDL-C) reductions of approximately 50% to 65% in patients with heterozygous familial hypercholesterolemia (HeFH), established cardiovascular disease, or high cardiovascular risk. Reductions in apolipoprotein B, non-high-density lipoprotein cholesterol, and lipoprotein(a) were also reported. Low-density lipoprotein cholesterol lowering was maintained through 72 weeks in an open-label extension. Treatment was generally well tolerated, although injection-site reactions occurred more frequently than with placebo.Relevance to patient care and clinical practice in comparison with existing drugs:Lerodalcibep-liga provides potent LDL-C lowering through a fixed, small-volume, once-monthly self-administered injection. Its efficacy is broadly comparable with other PCSK9-directed therapies, but direct comparative evidence remains limited. Analyses suggested a potential cardiovascular benefit, but this finding has not been confirmed in a dedicated, adequately powered cardiovascular outcomes trial.
Conclusions
Lerodalcibep-liga is an additional potent injectable PCSK9-directed treatment for adults requiring substantial LDL-C reduction, including those with HeFH. However, alirocumab or evolocumab may remain preferable when demonstrated cardiovascular event reduction is a major consideration in treatment selection.