Pharmaceutical companies think they have found the next frontier in heart attack prevention.
Novartis, amgen and Eli Lilly Some drug companies are betting that lowering levels of bad cholesterol, in particular, could be the next big hit in cardiology. All three major pharmaceutical companies are conducting late-stage trials testing whether drugs that cut Lp(a) can protect people from heart attacks.
If you can do that, your chances could be huge. An estimated 1 in 5 people around the world have elevated Lp(a), and there’s not much that can be done to lower it. Evidence from human genetics suggests this idea could work, but drug companies don’t know for sure. Novartis’ first late-stage trial results, expected later this year, will therefore be important for the overall pipeline.
“History teaches us not to make assumptions,” said Dr. Steve Nissen, chief academic officer of the Cleveland Clinic’s Heart, Vascular and Thoracic Institute and principal investigator of Novartis’ Phase 3 Horizon trial of the company’s experimental drug peracarsen to lower Lp(a). “We thought raising HDL would be beneficial, but that didn’t work. So I think we have to have an open mind.”
Lp(a), or lipoprotein(a), was first discovered in 1963. This is a more dangerous relative than the better-known LDL cholesterol, as it simultaneously clogs arteries and promotes blood clots, creating two risks with just one particle. Almost 50 years after Lp(a) was discovered, researchers found that people with high Lp(a) levels were more than twice as likely to have a heart attack than those without.
The amount of Lp(a) circulating in a person’s body is determined almost entirely by genes. Lifestyle factors such as diet and exercise do not affect Lp(a) levels as much as LDL levels, so there are few good options for lowering Lp(a) levels.
Doctors are now encouraging people to focus on factors they can change, such as lowering LDL cholesterol, lowering blood pressure, treating obesity and diabetes, and exercising. These strategies may help protect people from high Lp(a) for some time, Nissen said. New drugs may be able to treat people for longer periods of time.
Novartis, Amgen, and Lilly have already shown that their experimental drugs reduce Lp(a) levels by more than 80%. Now we need to show that it leads to tangible benefits. If that happens, the drug could reach $5.6 billion in annual sales by 2032, according to consensus estimates from pharmaceutical commercial information firm Evaluate.
“We don’t know how much it will take to bring the levels down,” Nissen said. “We don’t know how far levels need to be lowered for there to be a benefit from lowering them. Estimates of how low levels need to be lowered to prevent events based on genetic studies are highly variable, so we don’t have an answer. We won’t have an answer until the day we unblind the trial.”
That should happen around the middle of this year, Novartis CEO Basu Narasimhan said during the company’s fourth-quarter earnings call in February. The trial is investigating whether Novartis and its partner Ionis’ drug peracarsen prevents outcomes such as heart attacks and strokes in people who already have cardiovascular disease and have elevated Lp(a) levels. Novartis delayed releasing results by a year because people did not experience the event as quickly as the company expected in years of clinical trials.
Professor Narasimhan said it may have something to do with the fact that the researchers controlled for other risk factors in the participants. He said Novartis remains excited about the potential to look at this data and create “a whole new class of medicines that can help whole groups of patients who have no other options.”
Novartis’ drug uses a different mechanism than its next closest competitors, Amgen and Lilly. These drugs, Amgen’s olpasilan and Lilly’s leposisilan, appeared to be more potent in mid-term trials and led to greater Lp(a) reductions.
Amgen’s pivotal trial results were expected to be released late this year or early next year before the company postponed its schedule. The company currently says it plans to provide an update on timing in early 2027.
Jay Bradner, Amgen’s executive vice president of research and development, said it’s impossible to explain why it takes so long to analyze results for people who have had a heart attack without looking at the data.
“The clarity of the signal from population genetics and the encouraging signs (from early trials) make this a very smart bet,” Bradner said. He said Novartis’ upcoming results will provide direction on how Lp(a)-targeted drugs impact clinical outcomes, adding: “We are very bullish on this hypothesis.”
Lilly plans to share data from its Phase 3 study of leposisilane in 2029. All trials are designed slightly differently, which can lead to variations in results, said Dr. Michelle O’Donoghue, a cardiologist at Massachusetts General Brigham Heart and Vascular Institute and principal investigator of Amgen’s Ocean(a) trial of olpasilan.
“Therefore, there is reason to think that the magnitude of benefit may vary from program to program,” she said.
Despite attention from pharmaceutical companies, few physicians test their patients’ Lp(a) levels. One study of electronic health records found that less than 1% of adults in the U.S. were tested in 2024, and testing was concentrated in a few states.
Screening involves regular blood draws, similar to those used to measure other types of cholesterol. Major cardiology organizations recently began recommending that all adults undergo Lp(a) testing at least once in their lifetime. Nissen and O’Donoghue say some doctors are currently reluctant to test for a problem if they don’t have a drug to treat it.
The Family Heart Foundation plans to advocate for adding Lp(a) to standard lipid tests that measure other types of cholesterol, such as LDL, said Katherine Wilemon, the group’s CEO. Wilemon, who herself lives with elevated Lp(a) levels and another genetic heart condition, has been pushing for more testing since founding the organization in 2011 after experiencing a heart attack at age 38.
She said Lp(a) drugs are already helping to raise awareness about testing. If the treatment is successful in clinical trials, more screenings may be conducted. Morningstar analyst Jay Lee believes the market could take time to build, especially since Novartis’ peracalcen will initially be used in people with high Lp(a) levels and a history of cardiovascular events.
Amgen and Lilly are already testing whether the drug can protect people with elevated Lp(a) from that initial event. These results are still years away, with Lilly’s trial expected to be handed down in 2029.
In the meantime, Lily isn’t waiting to make further bets. The company has acquired a company that is testing daily pills and hopes to use gene editing to lower Lp(a) levels in a single treatment.
“There were a lot of shots in the basket,” said Cleveland Clinic’s Nissen. “I hope at least one of them reaches the goal.”
Goldman Sachs analyst Asad Haider said investors are skeptical. They are worried about how delays in Novartis’ trials will affect the drug, and even if the drug is effective, it could take years to become a blockbuster, he said.
“That’s why this Novartis case is going to be so important in how people think about unlocking,” Haider said.
Wilemon, of the Family Heart Foundation, believes there is a market for the drug. She believes screening is the most important issue and access is the second issue. She points to PCSK9 inhibitors, which are powerful drugs that lower LDL cholesterol levels, but the drugs struggled to gain widespread acceptance for years until drug companies lowered their prices.
But before adoption comes data. And she said she and the entire Lp(a) community have complained about the effectiveness of the Novartis drug.
