RNA therapeutics
Review maps twelve active Lp(a)-lowering drug trials, including three phase 3 outcome studies, still awaiting proof of cardiovascular benefit (Proc (Bayl Univ Med Cent) 2025)
Original title: Emerging pharmacological strategies in lipoprotein(a) reduction
Searching ClinicalTrials.gov as of May 2025, the authors identified twelve ongoing trials of targeted Lp(a)-lowering pharmacotherapy, noting that no published trial has yet shown that lowering Lp(a) alongside optimal LDL cholesterol control reduces atherosclerotic cardiovascular disease risk. Three large, multicentre phase 3 outcome trials assessing major adverse cardiac events are underway: Lp(a)HORIZON (NCT04023552, pelacarsen), OCEAN(a) (NCT05581303, olpasiran), and ACCLAIM-Lp(a) (NCT06292013, lepodisiran), alongside other ongoing phase 2 and phase 3 studies. The review frames these trials as the pending evidence needed to confirm whether pharmacological Lp(a) reduction translates into fewer cardiovascular events.
Original abstract
Background: Lipoprotein(a) (Lp(a)) is an low-density lipoprotein (LDL)-like particle whose elevation is considered a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis. Currently, there are no published clinical trials showing whether Lp(a) lowering in conjunction with optimal LDL cholesterol control reduces ASCVD risk.
Methods: Clinicaltrials.gov, an online database for clinical research studies, was used to identify ongoing clinical trials studying targeted Lp(a) lowering pharmacotherapy as of May 2025. Twelve clinical studies met the criteria and were included in this summary.
Results: The three large, multicenter phase 3 outcome trials evaluating clinical cardiovascular disease endpoints of major adverse cardiac event (MACE) are Lp(a)HORIZON (NCT04023552), OCEAN(a) (NCT05581303), and ACCLAIM-Lpa(a) (NCT06292013), which investigate pelacarsen, olpasiran, and lepodisiran, respectively. Other phase 2 and phase 3 trials are also under way.
Conclusion: Results from upcoming trials will inform us whether Lp(a) reductions translate to improved cardiovascular clinical outcomes.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.