Amgen has received regulatory clearance from South Korea’s Ministry of Food and Drug Safety to begin a Phase 3 clinical trial of its investigational heart drug, olpasiran. The study will assess the drug’s ability to lower the risk of major cardiovascular events in patients with elevated levels of lipoprotein(a), or Lp(a)—a cholesterol-related molecule linked to early heart attacks and strokes.
The randomized, placebo-controlled trial will enroll 179 patients across 14 hospitals in South Korea. The main goal is to determine whether olpasiran can help prevent first-time serious heart problems, such as coronary heart disease deaths, heart attacks, and emergency procedures to restore blood flow to the heart.
This new study builds on a previous Korean Phase 3 trial launched by Amgen in April 2023, which is focused on patients who already have atherosclerotic cardiovascular disease. That ongoing study is scheduled to conclude by January 2027.
Currently, there are no approved therapies that specifically lower Lp(a). This sticky, LDL-like particle is believed to be mostly inherited and not significantly influenced by diet or lifestyle changes. High levels of Lp(a) are recognized as an independent risk factor for conditions such as atherosclerosis, stroke, aortic valve disease, and other heart-related complications.
In addition to its primary objectives, the new trial will also measure several secondary outcomes. These include the time until cardiovascular death, ischemic stroke, and a broader group of adverse heart-related events. Researchers will monitor the percentage reduction in Lp(a) levels through week 48 of the study and will assess how the drug is processed in the body.
Olpasiran is a subcutaneous small interfering RNA (siRNA) therapy that works by targeting and degrading the mRNA in the liver responsible for producing Lp(a). In a previous Phase 2 trial, known as OCEAN(a)-DOSE, the drug reduced Lp(a) levels by more than 95% by week 36. Impressively, these reductions continued for nearly a year after treatment ended. Lp(a) levels remained 40% to 50% lower than baseline in patients who received olpasiran, compared to those who received a placebo.
Amgen is not alone in pursuing treatments for Lp(a)-linked cardiovascular risk. Novartis is currently conducting a Phase 3 trial of its candidate, pelacarsen, called Lp(a)HORIZON, which is expected to conclude in 2026. Meanwhile, Eli Lilly is advancing another experimental drug, lepodisiran, into Phase 3 after positive results from an earlier study showing long-lasting Lp(a) reductions.
This growing focus on lipoprotein(a) reflects a broader interest in targeting previously untreatable risk factors for heart disease. If successful, drugs like olpasiran could mark a major advance in preventive cardiology and fill a critical gap in current treatment options.
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