A groundbreaking medication shows unprecedented success in treating an overlooked genetic heart attack risk factor affecting millions of Americans.
At a Glance
- An experimental drug called lepodisiran reduced lipoprotein(a) levels by up to 94% in clinical trials
- Lipoprotein(a) is a genetically inherited heart disease risk factor previously considered untreatable
- The medication works by “silencing” the gene responsible for lipoprotein(a) production
- An estimated 64 million Americans have elevated lipoprotein(a) levels, increasing their risk of heart attacks and strokes
- Phase 3 clinical trials are currently underway to confirm if reducing these levels prevents cardiovascular events
Revolutionary Treatment Targets “Untreatable” Heart Disease Risk
A major breakthrough in cardiovascular medicine is emerging from recent clinical trials that could transform treatment for millions of Americans. The experimental drug lepodisiran has demonstrated remarkable effectiveness in targeting lipoprotein(a), a significant genetic risk factor for heart disease that has long been considered untreatable.
In a Phase 2 trial involving 320 patients from multiple countries, a single 400mg dose of lepodisiran reduced lipoprotein(a) levels by an astounding 94% over 180 days and maintained an 88.5% reduction over an entire year, with significant reductions lasting up to 540 days.
Unlike traditional cholesterol, lipoprotein(a) levels are genetically determined and remain relatively constant throughout life regardless of diet or exercise. This makes the condition particularly challenging to address with conventional treatments.
Current heart disease medications, including statins, do not effectively lower lipoprotein(a) levels, leaving an estimated 20-25% of the global population with elevated levels at increased risk for cardiovascular events. The trial results were presented at the American College of Cardiology’s annual meeting and published in the New England Journal of Medicine.
Understanding the “Silent” Cardiovascular Risk
Lipoprotein(a), often abbreviated as Lp(a), represents a particular type of cholesterol particle that is more prone to plaque buildup and blood clot formation than standard LDL cholesterol. Despite affecting approximately 64 million Americans, few people are aware of this risk factor, and it is rarely tested for by doctors due to the historical lack of effective treatments. The condition has no obvious symptoms until a cardiac event occurs, making it a silent but dangerous risk factor for many Americans who may otherwise believe their heart health is well-managed.
“Many people with high Lp(a) don’t experience symptoms, and unfortunately, it is not frequently tested,” said Steven Nissen, M.D.
Cleveland Clinic has described lipoprotein(a) as “one of the last untreatable frontiers of cardiovascular risk.” The study, led by Cleveland Clinic cardiologists and funded by Eli Lilly and Company, specifically targeted this frontier by utilizing gene-silencing technology to prevent the liver from producing the problematic protein. Dr. Steven Nissen, a lead researcher on the study, emphasized the importance of testing for lipoprotein(a) in patients with a personal or family history of heart disease.
How the Treatment Works and What’s Next
Lepodisiran works through a revolutionary approach called gene silencing, which effectively turns off the gene responsible for producing lipoprotein(a) in the liver. This differs from traditional medications that might target the protein after it’s already been produced. The therapy is administered as a single injection, with effects lasting potentially more than a year, making it a convenient option compared to daily medication regimens. In the clinical trial, the main side effects were mild injection site reactions reported in approximately 10-12% of participants.
“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,” concludes Dr. Nissen.
While the drug’s ability to lower lipoprotein(a) levels is now well-established, the crucial question remains whether this reduction will translate to fewer heart attacks and strokes. A larger Phase 3 trial is currently underway to determine if lepodisiran actually reduces cardiovascular events in at-risk patients.
At least four other pharmaceutical companies are also developing medications targeting lipoprotein(a), indicating growing recognition of this risk factor’s importance. Medical experts are now recommending that all adults have their lipoprotein(a) levels checked at least once, particularly those with a family history of early heart disease.
