A groundbreaking drug has reduced genetically inherited cholesterol by 94%, potentially revolutionizing heart disease prevention for millions who previously had no effective treatment options.
At a Glance
- A single dose of 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 up to 64 million Americans that increases heart attack and stroke risk
- Unlike traditional cholesterol, Lp(a) levels cannot be lowered through diet, exercise, or existing medications
- The Phase 2 trial involved 320 patients and showed the drug’s effects lasted up to 540 days with minimal side effects
- A larger Phase 3 trial is currently underway to determine if reducing Lp(a) levels actually prevents heart attacks and strokes
Understanding the “Hidden” Heart Risk Factor
An estimated 64 million Americans have elevated levels of lipoprotein(a), often abbreviated as Lp(a), a cholesterol-like particle that significantly increases their risk of heart attacks and strokes. Unlike the more familiar LDL cholesterol that responds to lifestyle modifications and statin medications, Lp(a) levels are genetically determined and remain relatively constant throughout life. This makes it one of the few major cardiovascular risk factors that doctors have been unable to address with existing treatments, despite its significant impact on heart health.
Lp(a) has remained largely under the radar in routine cardiovascular screening. Most adults have never had their Lp(a) levels checked, and many physicians don’t order the test since there haven’t been effective treatments available. The particle is more prone to plaque buildup and blood clots than standard LDL cholesterol, making it particularly dangerous for heart health. Affecting approximately 20-25% of the global population, Lp(a) has been described by Cleveland Clinic researchers as “one of the last untreatable frontiers of cardiovascular risk.”
Breakthrough Gene-Silencing Technology
The experimental drug lepodisiran works through a revolutionary approach called gene silencing. Rather than targeting the Lp(a) particles directly, the medication interferes with the genetic machinery that produces them in the first place. The Phase 2 clinical trial presented at the American College of Cardiology’s annual meeting showed remarkable results: a single 400mg injection reduced Lp(a) levels by 93.9% between days 60 and 180, with significant reductions persisting for up to 540 days – suggesting the potential for annual or even less frequent dosing.
The clinical trial involved 320 patients from multiple countries with a mean age of 62. The most common side effects were mild injection site reactions in about 12% of participants. The study, led by Cleveland Clinic and funded by Eli Lilly, represents a significant advancement in cardiovascular medicine, though researchers noted more investigation is needed in Black populations, who were underrepresented in the trial despite having higher average Lp(a) levels than other groups.
From Lab Results to Heart Attack Prevention
While the ability to dramatically lower Lp(a) levels represents a scientific triumph, the most important question remains unanswered: will reducing these levels actually prevent heart attacks and strokes? A larger Phase 3 trial is currently underway to determine if the remarkable laboratory improvements translate to better cardiovascular outcomes. At least four other pharmaceutical companies are also developing similar drugs, indicating significant industry confidence in this approach.
The potential impact of lepodisiran and similar medications in development extends beyond individuals already diagnosed with heart disease. Since Lp(a) levels are genetically determined and remain stable throughout life, early identification of those with elevated levels could allow preventive treatment before any cardiovascular damage occurs. Cardiologists are increasingly recommending that all adults have their Lp(a) levels checked at least once, particularly those with a personal or family history of premature heart disease or stroke.
The Future of Personalized Cardiovascular Risk Management
Dr. David Maron, a preventive cardiologist at Stanford, described the reduction in lipoprotein levels with lepodisiran as “thrilling.” The development of effective treatments for Lp(a) represents a significant advancement in the increasingly personalized approach to cardiovascular risk management. Rather than treating all patients with the same cholesterol-lowering medications, physicians can now identify specific risk factors and potentially target them with precision therapies.
For the millions of people worldwide with elevated Lp(a) levels, these developments offer new hope for reducing their cardiovascular risk. The once “untreatable” risk factor may soon join the list of modifiable cardiovascular risk factors alongside LDL cholesterol, blood pressure, and blood sugar. If the ongoing Phase 3 trial confirms that lowering Lp(a) reduces heart attacks and strokes, it would represent one of the most significant advances in preventive cardiology in recent decades, potentially saving countless lives through early identification and targeted treatment.
