Lp(a) drugs from Novartis, Amgen and Eli Lilly aim to prevent heart attacks

Pharma thinks it has found the next frontier in preventing heart attacks.

Novartis, amgen And Eli Lilly It is among drugmakers claiming that lowering levels of a particularly bad form of cholesterol will be the next blockbuster in cardiology. All three pharmaceutical giants are in late-stage trials to test whether drugs that block Lp(a) can protect people from heart attacks.

If they can, the opportunity could be huge: An estimated one in five people worldwide has elevated Lp(a), and there’s not much they can do to lower it. Evidence from human genetics suggests the idea could work, but drugmakers aren’t sure. This makes Novartis’ first late-stage trial results, expected later this year, important for the entire pipeline.

D., chief academic officer of the Cleveland Clinic Cardiovascular and Pulmonary Diseases Institute, who was the principal investigator of the Phase 3 Horizon study of pelacarsen, Novartis’ experimental drug to lower Lp(a). “History has taught us that you can’t make assumptions,” Steve Nissen said. “We thought raising HDL would be helpful, but that didn’t work, so I think we need to keep an open mind.”

Lp(a), or lipoprotein(a), was first discovered in 1963. It’s a more dangerous cousin of the well-known LDL cholesterol because it simultaneously clogs arteries and promotes blood clots, creating two risks in one particle. Almost 50 years after the discovery of Lp(a), researchers found that people with high Lp(a) levels were twice as likely to have a heart attack as those without Lp(a).

How much Lp(a) a person circulates in their body is determined almost entirely by their genes. Lifestyle factors such as diet and exercise do not affect Lp(a) levels the same way they do LDL levels, leaving people with few good options for reducing it.

Currently, doctors encourage 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 a while, Nissen said. New drugs could treat people for longer.

Novartis, Amgen, and Lilly have already proven that their experimental drugs reduce Lp(a) levels by more than 80%. Now they will need to show that this translates into tangible benefits. If that happens, the drugs could reach annual sales of $5.6 billion by 2032, according to consensus estimates from pharmaceutical business intelligence firm Evaluate.

“We don’t know how much you need to lower the levels,” Nissen said. “We don’t know how high you need to be to benefit from lowering your level. Estimates of how low you need to lower levels to prevent events based on genetic studies vary widely, so we don’t have an answer and won’t have an answer until the date we unblind the trial.”

Novartis CEO Vas Narasimhan said in the company’s fourth-quarter earnings call in February that this should happen by the middle of the year. The trial is investigating whether Novartis and partner Ionis’ drug pelacarsen can prevent outcomes such as heart attack and stroke in people with existing cardiovascular disease and high Lp(a) levels. Novartis delayed the reading by a year because people were not experiencing things as quickly as the company expected during years of testing.

Narasimhan said this may have to do with how researchers managed participants’ other risk factors. He said Novartis was excited to see the data and potentially create “an entirely new class of drugs that could help a group of patients who have no other options.”

Novartis’ drug uses a different mechanism than its closest competitors, Amgen and Lilly. These drugs, Amgen’s olpasiran and Lilly’s lepodisiran, appeared more effective in mid-stage trials, leading to greater reductions in Lp(a).

Amgen’s major trial results were expected later this year or early next year before the company pushed back its timeline. The company now says it plans to provide an update on timing in early 2027.

Jay Bradner, Amgen’s vice president of research and development, said it’s impossible to tell why it takes longer for a heart attack to occur without enough people to analyze the results without seeing the data.

“The clarity of the signal from population genetics and the encouraging signs from population genetics [earlier trials] “Make this a very smart bet,” Bradner said. The results from Novartis will provide direction on how drugs targeting Lp(a) may affect clinical outcomes, Bradner said, adding that he is “pretty optimistic about the hypothesis.”

Lilly expects to share data from its Phase 3 lepodisiran trial in 2029. D., a cardiologist at Mass General Brigham Heart and Vascular Institute and principal investigator of Amgen’s OCEAN(a) olpasiran trial. Michelle O’Donoghue said all trials were designed slightly differently, which could create differences in results.

“So there is reason to think that the magnitude of the benefit may be different in different programs,” he said.

Despite interest from drug manufacturers, few doctors test their patients’ Lp(a) levels. Less than 1% of adults in the US will be tested in 2024, according to a study of electronic health records, with testing concentrated in a few states.

Screening involves a routine blood draw, similar to those used to measure other types of cholesterol. Leading cardiology organizations have recently begun recommending that every adult be tested for Lp(a) at least once in their life. Currently, some doctors are reluctant to screen people for a problem when they don’t have medications to treat it, Nissen and O’Donoghue said.

The Family Heart Foundation plans to advocate for the addition of Lp(a) to the standard lipid test that measures other types of cholesterol, such as LDL, said Katherine Wilemon, CEO of the Family Heart Foundation. Wilemon, who lives with high Lp(a) and another genetic heart condition himself, has been pushing for more screening since he had a heart attack at age 38 and founded the organization in 2011.

He said Lp(a) medications helped raise awareness about testing. If treatments are successful in clinical trials, more screening may be available. Morningstar analyst Jay Lee thinks it may take time to establish the market, especially given that Novartis’ pelacarsen will initially be used for people with high Lp(a) levels and a history of cardiovascular events.

Amgen and Lilly are currently testing whether the drugs can protect people with elevated Lp(a) from this first episode. Lilly’s lawsuit is expected to conclude in 2029. These results are still years away.

Lilly, meanwhile, doesn’t expect to place any more bets. The company is testing a daily pill and has acquired a company that wants to use gene editing to lower Lp(a) levels in a one-time treatment.

“We have a lot of shots on goal,” said Cleveland Clinic’s Nissen. “We hope at least one of them ends up in the back of the net.”

Goldman Sachs analyst Asad Haider said investors were skeptical. He said they’re worried about what the delay in Novartis’ hearing means for the drugs, and that even if the drugs work, it could take years for them to become a big blockbuster.

“That’s why this Novartis case is so important to how people think about unlocking,” Haider said.

Wilemon of the Family Heart Foundation thinks the drug market is there. He sees screening as the most important issue and access as the second issue. He points to PCSK9 inhibitors, powerful drugs that lower LDL cholesterol levels, that struggled to gain traction for years until drugmakers lowered their prices.

But before the acquisition comes the data – he said he and the entire Lp(a) community got their hands on Novartis’ drug dealings.