Lipoprotein(a) Lowering with Pelacarsen (TQJ230)

Background: Elevated levels of lipoprotein(a) have been linked to an increased risk of Atherosclerotic Cardiovascular Disease (ASCVD). Conventional lipid-lowering medications have modest to no impact on Lp(a) levels. Emerging RNA-based modalities significantly decrease Lp(a) by silencing the apo(a) mRNA at the post-transcriptional level. Pelacarsen (TQJ230) is a GalNAc-conjugated novel Antisense Oligonucleotide (ASO) that selectively inhibits apo(a) synthesis in hepatocytes. Objective: This updated review aims to elucidate the mechanism of action, pharmacokinetics, clinical efficacy, and safety profile of Pelacarsen (TQJ230), with a focused appraisal of its potential role in the prevention of Atherosclerotic Cardiovascular Disease (ASCVD). Methodology: We conducted a literature search on PubMed, Google Scholar, and Scopus using keywords such as "Pelacarsen", "antisense oligonucleotide" OR “ASO”, and "lipoprotein(a)" from inception to March 2025. Results: Pelacarsen demonstrated a dose-dependent sustained reduction in Lp(a) levels, achieving up to a 97% reduction at the highest dose in Phase 1 and 2 trials. It was well-tolerated with a favorable safety profile. Phase 3 trials are underway to provide robust data on its long-term safety and impact on Atherosclerotic Cardiovascular Disease (ASCVD) outcomes. Conclusion: Pelacarsen (TQJ230) is a potent Lp(a)-lowering agent with promising efficacy and a favorable safety profile. However, its definitive role in reducing atherosclerotic cardiovascular events remains to be established. Ongoing Phase 3 trials will be critical in determining whether its lipid-lowering effects translate into meaningful long-term cardiovascular outcomes.