A fatty particle can clog arteries just as surely as cholesterol but often goes undetected, striking seemingly healthy people unaware of the danger. Though tests are widely available, they aren’t routinely ordered — in part because there are no approved treatments for the genetic disorder.
Now, cardiologists waging a campaign against lipoprotein(a) say they are reaching a turning point. Five experimental drugs are in late stages of development and aim to prove that lowering levels of Lp(a) — pronounced “L-P-little-A” — reduces heart attacks and strokes. Results from the most advanced clinical trial are expected in the first half of 2026.
Cardiologists, drugmakers and Wall Street analysts are optimistic that these new drugs can effectively treat a disorder that is estimated to affect about 20 percent of the world’s population. Yet even if they prove effective, the cost of a novel drug — as well as the scant public awareness of Lp(a) — could be a barrier to treating patients who might benefit.
“There are over a billion people on our planet that have elevated lipoprotein levels and that are at increased risk,” said Steve Nissen, a cardiologist at Cleveland Clinic whose team is leading trials on four drugs targeting Lp(a). “We will have a massive educational job to do.”
Discovered in the 1960s, Lp(a) is prone to getting stuck in the arterial wall like the particle that doctors call “bad” cholesterol, but it carries another protein that creates an even greater risk of heart attacks, strokes and restricting blood flowing from the heart. Until 2019, there wasn’t even a diagnostic code for high Lp(a) levels.
The condition often flies under the radar because it is almost entirely genetic, isn’t part of typical cholesterol tests and can afflict otherwise healthy people. Diet and exercise don’t bring down Lp(a). With no approved drugs to treat the condition, many cardiologists say they routinely hear that primary care physicians don’t see the point in testing. In a study of more than 48,000 patients globally with a history of heart disease, just 14 percent had been screened for Lp(a).
So the cardiology community is closely watching a clinical trial seen as a bellwether for Lp(a) treatments.
The trial is studying pelacarsen, an experimental drug that stops the liver from producing the extra protein carried by Lp(a) that makes it especially risky. In an earlier trial, researchers showed the drug could reduce Lp(a) levels by up to 80 percent when injected weekly. Now the drug’s sponsor, Novartis, will be the first to reveal whether lowering Lp(a) levels also reduces cardiovascular events from patients who have heart disease.
Asked about pricing strategy on a November call with financial analysts, Novartis executives said that pelacarsen would initially be tailored to patients who’ve had early heart problems and a family history of disease, according to a transcript compiled by S&P Global Market Intelligence. “The family history is an emotional motivator for people to take action,” said Dianne Auclair Rocha, a senior vice president.
Though pelacarsen is the farthest along, other experimental drugs have shown they can lower Lp(a) even more sharply and for longer. Olpasiran, developed by Amgen, cut Lp(a) levels by up to 100 percent when taken every 12 weeks. Eli Lilly is studying lepodisiran, which works by a similar mechanism, to see if it reduces risk for patients who have not yet had a cardiac event — and it is also developing a pill for lowering Lp(a).
“If these therapies show benefit, it would impact the lives of these individuals tremendously,” said Gissette Reyes-Soffer, an associate professor at Columbia University Irving Medical Center who advises companies targeting Lp(a). “You’re not going to have four stents put in,” she said, adding that preventing heart disease could save on health costs.
For now, there are few ways to lower Lp(a) levels. A class of cholesterol-lowering drugs has shown a modest effect, and an expensive blood-filtering procedure can also do so, though neither is approved by the Food and Drug Administration for that purpose. But some cardiologists bristle at physicians who decline to order tests for Lp(a) because there isn’t a drug that treats it.
“I think that’s crazy,” said Erin Michos, a professor of cardiology at the Johns Hopkins University School of Medicine. “I think Lp(a) is very actionable now,” she said, adding that physicians can take steps to lower all other treatable risks such as high cholesterol, blood pressure and weight. Michos has consulted for companies developing Lp(a) therapies.
Labcorp and Quest Diagnostics offer Lp(a) in-person tests for about $50. The Family Heart Foundation, which promotes awareness of genetic risks for cardiovascular disease, offers free at-home kits to test for Lp(a). Guidelines from professional associations differ, with some calling for everyone to get tested once while others recommend screening only those deemed to be at high risk.
That may change with the results of the pending clinical trials on lowering Lp(a).
“If these trials are positive, I think they are going to be game changers,” said Salim Virani, a preventive cardiologist who is now vice provost at Aga Khan University in Pakistan. But that will also depend on how they are priced, he said, an issue that has limited access to other effective cardiovascular drugs. “Drugs only benefit when patients are able to take them,” he said.
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