Revolutionary New Drug Targets ‘Stealthy’ Cholesterol Impacting 1 in 5 People

Recent studies highlight the importance of addressing “stealthy cholesterol,” a significant heart health risk affecting approximately 1 in 5 individuals. This condition is connected to lipoprotein(a), or Lp(a), which is largely influenced by genetics. Traditional lifestyle changes like diet and exercise have little to no effect on Lp(a) levels, making awareness and new treatments crucial. The promising drug, lepodisiran, could revolutionize how we manage this hidden cardiovascular risk, potentially slashing Lp(a) levels by up to 95% based on early trial results.

The groundbreaking research published in the New England Journal of Medicine focuses on lepodisiran, an innovative drug that targets lipoprotein(a), often referred to as “stealthy cholesterol.” This condition goes unnoticed in many cases and contributes significantly to cardiovascular diseases, heart attacks, and strokes.

Approximately 64 million Americans and about one in five people worldwide are estimated to have elevated Lp(a) levels, often without awareness. The major concern is that stealthy cholesterol typically exhibits no symptoms and is not identified during conventional cholesterol screenings. Historically, the absence of effective treatments has led to limited testing for Lp(a) levels.

Dr. Corey Bradley, a cardiologist at NewYork-Presbyterian/Columbia University Irving Medical Center, stated, “We’ve never before had a way to lower it. Often, if we can’t treat something, we don’t necessarily measure it.” However, with the advent of lepodisiran, there is hope for a decisive move toward effectively managing this deadly type of cholesterol.

Understanding Stealthy Cholesterol

Lipoprotein(a), or Lp(a), is structurally similar to the more familiar LDL (“bad”) cholesterol. Each Lp(a) particle consists of an LDL particle combined with an additional protein.

This unique combination poses a double threat to cardiovascular health. According to Dr. Bradley, Lp(a) not only contributes to artery clogging when present at elevated levels but also facilitates blood clotting and inflammation, enhancing the risk of cardiovascular issues.

Another crucial factor regarding Lp(a) is that its levels are primarily determined by genetics. Unlike lifestyle factors that can fluctuate over time, Lp(a) remains relatively constant throughout one’s life. Dr. Adedapo Iluyomade, a preventive cardiologist, notes: “You can lose 100 pounds, eat a well-balanced diet, stop smoking, and exercise—and your lipoprotein(a) will remain stable.”

Common medications that effectively lower LDL cholesterol, such as statins, do not impact Lp(a) levels. New advancements like lepodisiran, specifically targeting Lp(a), hold great potential to be transformational in preventive cardiology, as suggested by Dr. Iluyomade.

Introducing Lepodisiran: A Potential Game-Changer

Lepodisiran is an injectable medication designed to lower Lp(a) levels by inhibiting its production in the liver. It underwent initial human trials in 2023 and was found to be both safe and well-tolerated, effectively bringing Lp(a) levels to undetectable levels for almost a year.

In a recent Phase 2 trial presented at the American College of Cardiology 2025 Scientific Sessions, around 300 adults with elevated Lp(a) were administered either a placebo or varying doses of lepodisiran. Notably, those receiving the highest dose (400 milligrams) experienced an average 94% reduction in Lp(a) levels after six months. Remarkably, even after one year, Lp(a) levels remained nearly 90% lower than the trial’s onset.

Patients receiving a second injection of 400 milligrams six months later reported even more significant benefits, achieving an approximately 95% reduction in Lp(a) levels.

Dr. Steven Nissen, the lead author of the study and chief academic officer at the Cleveland Clinic, expressed enthusiasm for the findings: “What we have is a very effective therapy…and lowering [lipoprotein(a)] for a long period of time with relatively infrequent administration.”

Significantly, lepodisiran has shown to be both safe and well-tolerated by participants, with no serious side effects reported, although some did experience temporary side effects such as redness and itching at injection sites.

Future Prospects for Lepodisiran

While lepodisiran is not yet available for general use, further research is essential to determine whether lowering Lp(a) levels will effectively reduce the risk of heart complications. Dr. Nissen’s team is investigating this critical question in their ongoing Phase 3 trial—a process that may take several years.

In parallel, other pharmaceutical companies are exploring similar Lp(a)-targeting medications, with some advancing further along in clinical trials. There is cautious optimism in the research community that either lepodisiran or a comparable treatment could soon be accessible to those with elevated Lp(a) levels.

“Surprises can happen,” Dr. Nissen cautioned. “Not everything that seems logical happens.”

Steps You Can Take Today

Despite the absence of an approved treatment, individuals can take proactive measures to safeguard their heart health. Getting your Lp(a) levels tested is a vital first step. A simple blood test can identify Lp(a) levels, with many insurance providers covering the costs. The National Lipid Association suggests that every adult should be tested for Lp(a) at least once in their lifetime.

Dr. Iluyomade emphasizes the stability of Lp(a) levels: “They remain stable throughout life, so there’s no need for repeated testing.” If high Lp(a) levels are identified, healthcare professionals may focus on altering other modifiable risk factors for heart disease, including:

• Lowering LDL cholesterol
• Managing blood pressure
• Maintaining a healthy body weight
• Controlling diabetes
• Encouraging a physically active lifestyle

“By addressing these other risk factors, we can ensure patient safety until more advanced therapies are developed,” Dr. Nissen remarked. Knowing your Lp(a) levels offers you valuable insight into your health status.

“It’s a great opportunity for patients to know what their risk is and advocate for themselves,” Dr. Bradley concluded.