13 Lp(a): A Toolkit for Healthcare Professionals Three RNA-targeting drugs that lower Lp(a) >80% are in Phase 3 cardiovascular outcomes trials. Emerging Therapies that specifically and effectively lower Lp(a) There are three compounds (pelacarsen, olpasiran and lepodisiran) that are in Phase 3 clinical trials. Pelacarsen is an antisense oligonucleotide (ASO) that targets apo(a) messenger RNA and lowers Lp(a) by ~80%. This compound is currently being tested in a Phase 3 cardiovascular outcomes trial (Lp(a) HORIZON; NCT04023552). z 8323 participants; randomized, double-blind, placebo-controlled trial z Key inclusion criteria: Lp(a) ≥ 70 mg/dL; pre-existing ASCVD z Primary endpoint: time to expanded major adverse cardiovascular event (Lp(a) ≥ 70 mg/dL or ≥ 90 mg/dL) z Study has been completed and the primary end point was not met Olpasiran is a silencing RNA compound (siRNA) that targets apo(a) messenger RNA and lowers Lp(a) by >90%. This compound is currently being tested in a Phase 3 cardiovascular outcomes trial (OCEAN(a); NCT05581303) z 7297 participants; randomized, double-blind, placebo-controlled trial z Key inclusion criteria: Lp(a) ≥ 200 nmol/L; history of ASCVD z Primary endpoint: time to CHD death, myocardial infarction, or urgent coronary revascularization z Anticipated study completion date is December 2026 z OCEAN(a)-PreEvent (NCT07136012) is enrolling participants with Lp(a)≥ 200 nmol/L at risk for a first major cardiovascular events, with a completion date of October 2031
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