Novartis Drug Cut Lp(a) by 80% but Missed Its Heart Trial Goal. Full Data Due Saturday

A drug that slashes a genetically driven cholesterol particle did not prevent heart attacks in a large trial. That is the problem now facing Novartis, its partner Ionis Pharmaceuticals, and a field of drugmakers betting billions on the same target.

The drug is pelacarsen. Novartis said its Phase 3 trial did not meet its main goal of reducing cardiovascular risk. The primary measure was a composite of death, heart attack, stroke and procedures to restore blood flow.

Pelacarsen lowered blood levels of lipoprotein(a), known as Lp(a), by as much as 80%. That did not translate into a lower risk of heart attack and stroke.

What Lp(a) is and why it matters

Around 20% of people carry genes that tell the liver to make this extra-sticky cholesterol particle. Levels vary from person to person. Incidence is higher among people of African or South Asian ancestry.

Unlike standard LDL cholesterol, Lp(a) does not respond to diet, exercise or lifestyle changes. It is set by genetics.

Heart disease kills nearly a million people a year in the United States, according to the American Heart Association. Doctors have long wanted a drug for the patients whose risk comes from Lp(a), because nothing else moves the number.

The open question: cause or marker

The trial failure revives an old argument. Is Lp(a) driving heart disease, or is it simply a flag that shows who is at risk?

Dr. Parag Joshi, a cardiologist at UT Southwestern Medical Center in Dallas and an investigator on the study, said the answer will shape the field. "If there are no signals at all, then that will really dampen any further enthusiasm for the space," he said.

Cardiologists will look at whether the trial narrowly missed statistical significance, showed no effect, or showed harm. They plan to focus on heart attack and revascularization rates.

Doctors have also raised questions about patient dropouts, the composite endpoint and the use of PCSK9 drugs during the trial. The trial tested a monthly 80-milligram dose.

Rivals say their drugs are different

Pelacarsen is not the only Lp(a) drug in development. Amgen's olpasiran and Eli Lilly's lepodisiran have each lowered Lp(a) by around 95% in studies.

Amgen expects Phase 3 results in early 2028. Lilly expects its results in 2029.

Both companies point to design differences. Their trials enroll only patients with higher Lp(a) levels than many of those in the Novartis study.

Paul Burton, Amgen's chief medical officer, said he will watch the data at the AHA meeting. "We believe we have a differentiated molecule," he said.

That is the companies' position. Whether a deeper cut in a higher-risk group changes the outcome will not be known until those trials report.

Testing is already standard advice

Lp(a) blood testing is already in clinical use. The AHA and the American College of Cardiology issued guidelines earlier this year recommending that every adult have Lp(a) measured at least once.

Dr. Nathaniel Lebowitz, a cardiologist, said the particle shows up often in patients with a family history of early heart disease. "When I see someone with a family history of premature heart disease, there is a 95% chance it's going to be from LP little a," he said.

That creates an awkward gap. Patients are being told to learn their number, while the first large outcomes trial of a drug that lowers it has come up short.

What comes next

Full pelacarsen results will be presented Saturday, Nov. 7, at the AHA's annual scientific meeting in Chicago. The data will show the size and direction of any effect on heart attacks, strokes and revascularization.

They will also show whether the trial narrowly missed or found nothing. That will determine how much weight Amgen's and Lilly's later trials carry.