Lp(a) is increasingly recognized as the “forgotten risk factor” in cardiovascular disease. While it long seemed untreatable, researchers are now focusing on new targeted therapies designed to directly lower Lp(a) levels. Here’s an overview of what is happening worldwide in research and drug development.

Ongoing clinical studies on Lp(a)
Across the globe, large-scale clinical trials are underway to study the role of Lp(a) in heart and vascular diseases. The key question is whether lowering Lp(a) truly leads to fewer heart attacks, strokes, and valve diseases.

Major ongoing studies:

• Lp(a) HORIZON Study – investigates Pelacarsen (an antisense therapy) in thousands of participants with existing cardiovascular disease.
• OCEAN(a) Study – tests olpasiran, a siRNA drug that inhibits the production of apolipoprotein(a).
• Lepodisiran – showed a 94% reduction in Lp(a) levels lasting up to six months in early-stage trials.
• Muvalaplin – a new oral therapy that prevents apo(a) from binding to apoB, reducing the formation of Lp(a).

These studies will help determine how much lowering of Lp(a) is clinically meaningful and which therapies could become standard in the near future.

New therapies in development
New treatments no longer target cholesterol itself, but rather the liver, where Lp(a) is produced. By blocking the production of the apolipoprotein(a) protein, Lp(a) levels can be reduced by 80 to 90%.

Key treatments in development:

• Pelacarsen (Novartis/Ionis) – an antisense therapy in Phase 3 trials; lowers Lp(a) by approximately 80%.
• Olpasiran (Amgen) – a siRNA drug currently in Phase 3; administered once every 12 weeks.
• Zerlasiran (Silence Therapeutics) – shows similar reductions in Lp(a) with long-lasting effects.
• Muvalaplin (Eli Lilly) – the first oral therapy in development; prevents the formation of Lp(a).
• Lepodisiran (Eli Lilly) – a long-acting RNA-based drug showing strong reductions after a single dose.

These medicines are still under investigation, but first approvals are expected around 2027–2028, depending on the outcomes of ongoing Phase 3 clinical trials.

The future of Lp(a) screening and guidelines

Because Lp(a) levels are genetically determined and elevated in about one in five people, more and more experts are advocating for one-time universal screening of Lp(a) in all adults. New guidelines from leading cardiology societies, including the European Atherosclerosis Society (EAS) and the American Heart Association (AHA) anticipate that Lp(a) testing will soon become a standard part of cardiovascular risk assessment.

Key Developments:

• Future guidelines are expected to recommend that every adult be tested for Lp(a) at least once in their lifetime.
• Screening is especially encouraged for individuals with a family history of premature heart or vascular disease.
• Upcoming treatment protocols will likely include a combination of Lp(a)-specific therapies and traditional cholesterol-lowering strategies.