Mohammad T Alashqar, Nikolas Lako, Milap C Nahata
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.
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.