Researchers have developed an experimental drug that can drastically reduce a cholesterol-like particle in the blood, known to increase the risk of heart attacks and strokes.
This particle, called lipoprotein(a) or Lp(a), is found in elevated levels in about 20–25% of people globally. In the United States alone, an estimated 64 million people have high Lp(a) levels, though many remain unaware of it.
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Unlike other forms of cholesterol, Lp(a) levels cannot be lowered through lifestyle changes such as diet or exercise. Genetics play a key role, and until now, there have been no approved treatments to target it. The Cleveland Clinic, which led the new study, has described Lp(a) as “one of the last untreatable frontiers of cardiovascular risk”.
A new hope: Lepodisiran
The drug being tested, Lepodisiran, is made by Eli Lilly, which also funded the research. It works by “silencing” the gene that produces Lp(a), effectively stopping the body from making it. The study was published in the New England Journal of Medicine and presented at the American College of Cardiology’s annual conference on March 30.
Earlier research hinted at the drug’s potential, and the new findings back that up strongly. In a trial involving 320 people from 10 countries, participants were given either a placebo or one or two doses of Lepodisiran via injection. Their average Lp(a) levels were about 250 nanomoles per litre, more than three times the normal upper limit of 75.
After just one high-dose injection, Lp(a) levels dropped by nearly 100% within six months. Those who received a second dose maintained this drop for up to a year.
Dr Steven Nissen of the Cleveland Clinic, the study’s lead author, said the drug “removed virtually all lipoprotein(a) from the blood”.
Why Lp(a) matters
Lp(a) is similar to “bad” LDL cholesterol, but is even more dangerous when it comes to plaque build-up and blood clots in the arteries. Dr Nissen noted that while LDL levels are influenced by multiple genes and lifestyle, Lp(a) is determined almost entirely by a single gene, and levels remain constant throughout life.
“You only need to measure it once,” he said. “Whatever your level is at age 24 is the same at 64.”
Dr Deepak Bhatt, a cardiologist at Mount Sinai in New York (not involved in the study), added, “Lipoprotein(a) is an independent risk factor for heart disease that is largely determined by genetics.”
Encouraging but early results
While the drug appears safe so far — only 12% of participants reported mild injection site reactions — researchers acknowledged a few limitations.
The trial involved only two doses, so the effects of more frequent dosing are unknown.
The number of Black participants was low, despite data showing they are more likely to have elevated Lp(a). A larger phase 3 trial is now enrolling more diverse participants.
Most importantly, while Lp(a) levels dropped remarkably, the study did not show whether this also led to fewer heart attacks or strokes.
“We need a phase 3 trial to confirm whether reducing Lp(a) will lower heart attack risk,” Dr Bhatt said. Dr Nissen confirmed such a trial is already underway.
A one-time test with lifelong relevance
Experts are now urging more people to get their Lp(a) levels tested — even if it’s just once.
“Unlike traditional cholesterol, Lp(a) doesn’t change over time. So testing it once is enough to assess your risk,” said Dr Nissen.
Organisations like the European Society of Cardiology and the US National Lipid Association recommend that all adults have their Lp(a) levels checked at least once.