PCSK9 Monoclonal Antibodies: New Developments and Their Relevance in a Nucleic Acid-Based Therapy Era

To report on recent data about PCSK9 monoclonal antibodies and to evaluate their relevance in a nucleic acid-based therapy era for lipid lowering and prevention of cardiovascular disease.

New methods of PCSK9 inhibition based on nucleic acid therapeutics such as antisense oligonucleotides, small interfering RNAs, and CRISPR tools for therapeutic gene editing are reported, and interesting new data regarding the clinical relevance of PCSK9 antibodies are discussed. Promising methods of PCSK9 inhibition are in development, and one of them, the siRNA inclisiran targeting PCSK9, has already been approved for clinical use. However, PCSK9-mAb remains the PCSK9-inhibiting tool with the longest safety data and the only one having positive cardiovascular outcome trials. An ongoing cardiovascular outcome trial with inclisiran is planned to be completed in 2026. Other forms of PCSK9 inhibition, such as antisense oligonucleotides targeting PCSK9 and CRISPR base editing of PCSK9, are still in early phases of development, and their potential clinical relevance remains to be established.