New Drug Could CHANGE Everything
A groundbreaking new drug shows remarkable promise in eliminating a genetic risk factor for heart disease that affects millions of Americans previously considered untreatable.
At a Glance
- The experimental drug lepodisiran reduced lipoprotein(a) levels by 94% over 180 days in clinical trials
- Lipoprotein(a) is a genetically inherited risk factor affecting an estimated 64 million Americans
- Unlike traditional cholesterol, Lp(a) levels cannot be lowered through diet, exercise, or existing medications
- A single 400mg dose maintained significantly reduced levels for up to 540 days
- Phase 3 trials are underway to determine if reducing Lp(a) prevents heart attacks and strokes
A New Frontier in Cardiovascular Medicine
American researchers have developed a drug that targets what Cleveland Clinic experts call “one of the last untreatable frontiers of cardiovascular risk.” The experimental medication lepodisiran showed remarkable effectiveness in clinical trials, reducing lipoprotein(a)—a substance linked to increased heart attack and stroke risk—by up to 94%. Unlike traditional cholesterol, lipoprotein(a), or Lp(a), is determined almost entirely by genetics and has proven resistant to lifestyle changes and current medications, leaving millions vulnerable to cardiovascular events despite otherwise healthy habits.
The breakthrough findings were presented at the American College of Cardiology’s annual meeting and simultaneously published in the New England Journal of Medicine. In the Phase 2 trial involving 320 patients across multiple countries, a single 400mg dose of lepodisiran maintained significantly reduced Lp(a) levels for up to 18 months, with minimal side effects reported. This represents a potential paradigm shift in how doctors approach cardiovascular risk management, especially for patients with family histories of early heart disease.
Understanding the Hidden Heart Disease Risk
Lipoprotein(a) remains largely unknown to the general public despite affecting approximately 20-25% of the global population. The particle is more prone to plaque buildup and clotting than traditional LDL cholesterol, creating significant cardiovascular risk even in otherwise healthy individuals. Most concerning to medical experts is that many people with elevated levels experience no symptoms until suffering a cardiovascular event, and traditional cholesterol-lowering medications have minimal impact on Lp(a) levels.
“Many people with high Lp(a) don’t experience symptoms, and unfortunately, it is not frequently tested,” explains Steven Nissen, M.D. “It is important for patients with a personal or family history of heart disease to speak with their physician about having an Lp(a) blood test.”
Experts note that Lp(a) levels remain relatively constant throughout a person’s life due to genetic factors, making it an easy risk factor to identify with a simple blood test. However, testing has historically been limited because doctors had no effective treatments to offer patients with elevated levels. The development of lepodisiran and similar drugs under development could fundamentally change this situation, making widespread testing more valuable and actionable.
How the New Therapy Works
Lepodisiran represents a revolutionary approach using gene-silencing technology to address cardiovascular risk. The drug works by targeting the genetic mechanism responsible for producing lipoprotein(a) in the liver, effectively “silencing” the problematic gene. By suppressing this production at its source, researchers have achieved reduction levels previously thought impossible with conventional medicine. The study was led by Cleveland Clinic researchers and funded by pharmaceutical company Eli Lilly.
“There is no approved pharmacotherapy for lipoprotein(a) by regulatory authorities in any country in the world,” states Steven Nissen, M.D. “Effective therapies to reduce Lp(a) are being developed and if they show a reduction in risk of heart attack or stroke, we need to know whom to treat.”
The trial reported mild injection site reactions in approximately 12% of participants as the primary side effect. Researchers noted a need for additional research in Black populations, who were underrepresented in the initial trials. A larger Phase 3 trial is currently underway to determine whether the dramatic reduction in Lp(a) levels translates into fewer heart attacks and strokes—the ultimate goal of this pioneering cardiovascular therapy.
