Pelacarsen for lowering lipoprotein(a): implications for patients with chronic kidney disease

Area of Science:

• Nephrology
• Cardiology
• Pharmacology

Background:

• Chronic kidney disease (CKD) patients have elevated cardiovascular disease (CVD) risk.
• Statins' efficacy is limited in advanced CKD, potentially due to increased lipoprotein(a) [Lp(a)] and PCSK9 levels.
• Elevated Lp(a) is linked to atherosclerosis and calcific aortic stenosis, common in CKD.

Discussion:

• Pelacarsen, an antisense oligonucleotide targeting the *LPA* gene, demonstrated significant dose-dependent Lp(a) reduction (35-80%) in a Phase 2 trial for CVD patients.
• The exclusion of patients with moderate to severe CKD from pelacarsen trials limits understanding of its cardiovascular benefits in this high-risk population.
• Further investigation is needed to clarify the role of Lp(a) in CVD development and progression within the context of CKD.

Key Insights:

• Lipoprotein(a) [Lp(a)] is a critical atherogenic molecule implicated in cardiovascular disease, particularly in chronic kidney disease (CKD) patients.
• Pelacarsen shows promise in lowering Lp(a) levels, offering a potential new therapeutic avenue for cardiovascular risk reduction.
• Current clinical trial exclusions for patients with significant kidney disease hinder the evaluation of pelacarsen's efficacy and safety in CKD.

Outlook:

• A planned Phase 3 trial (Lp(a)HORIZON) aims to further assess pelacarsen's efficacy and safety, with enrollment planned from 2020 to 2024.
• Optimizing exclusion criteria to include CKD patients in future trials is crucial for understanding Lp(a) 's role in CVD within this population.
• Research into Lp(a) modulation in CKD could lead to improved cardiovascular outcomes for a vulnerable patient group.