RNA therapeutics
Only apheresis is FDA-approved for Lp(a) today, review of the RNA-therapeutics pipeline moving to phase 3 outcomes trials (J Clin Lipidol 2026)
Original title: Emerging therapies to lower lipoprotein(a) and the current clinical trials landscape: RNA-therapeutics and beyond
Review of the Lp(a)-lowering treatment landscape, noting that lipoprotein apheresis remains the only FDA-approved therapy for Lp(a) reduction today. PCSK9 inhibitor monoclonal antibodies and siRNA therapeutics developed primarily for LDL-C lowering show modest incidental Lp(a) reductions, while Lp(a)-targeted antisense oligonucleotides, siRNA therapeutics and small-molecule inhibitors produce significant reductions in phase 2 trials. Several of these targeted agents have now progressed into phase 3 cardiovascular outcomes trials, which will determine whether reducing Lp(a) lowers major adverse cardiovascular events across different patient groups, baseline Lp(a) elevations, and absolute or percentage reductions achieved.
Original abstract
Background: Lipoprotein(a) [Lp(a)] is a genetically determined, independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease. Currently, the only Food and Drug Administration-approved treatment for Lp(a) reduction is lipoprotein apheresis. Emerging targeted pharmacotherapies have shown significant reductions in Lp(a) levels in phase 2 trials. Phase 3 trials are currently underway to assess whether those significant Lp(a) reductions reduce the risk of major adverse cardiovascular events (MACE).
Sources Of Material: PubMed, ClinicalTrials.gov. ABSTRACT OF FINDINGS: Certain lipid-lowering pharmacotherapies, such as proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibodies and small-interfering RNA therapeutics, have shown modest reductions in Lp(a) in conjunction with their primary low-density lipoprotein cholesterol-lowering effect. Lp(a)-targeted pharmacotherapies, such as antisense oligonucleotides, small interfering RNA therapeutics, and small molecule inhibitors, significantly reduce Lp(a) levels in phase 2 clinical trials.
Conclusion: The Lp(a) clinical trials landscape now includes multiple therapies in development, including several in phase 3 CV outcomes trials. Results are highly anticipated and will reveal whether significant Lp(a) reduction prevents MACEs in various groups of patients with different forms of ASCVD or CV risk factors, different degrees of baseline Lp(a) elevation, and in the setting of different absolute and percentage reductions in Lp(a).
apheresisPCSK9 inhibitionRNA therapeuticstherapy
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.