A large trial of a drug designed to lower Lp(a), a cholesterol-carrying particle whose level is set mostly by genes, has missed its main goal. The drug, pelacarsen, was developed by Novartis and Ionis Pharmaceuticals. It lowered Lp(a) levels by about 80 per cent, but that drop did not come with a statistically significant reduction in a combined measure of heart deaths, heart attacks, strokes and urgent procedures to reopen blocked arteries1. The result has raised fresh questions about whether lowering this inherited particle reduces heart disease1.
Novartis first announced the headline result on September 4, 2026, saying the trial “did not meet its primary endpoint,” meaning its main pre-set goal, compared with a placebo (a dummy treatment)2. Detailed results have not been released yet and are scheduled for presentation at the American Heart Association’s annual scientific meeting in Chicago1.
What the trial tested
The study, called Lp(a)HORIZON, was the final large test of the kind used to support approval, and it was registered with the code number NCT040235523. It enrolled 8,323 people who had high Lp(a) and already had heart or artery disease, such as a past heart attack or stroke43. Participants were randomly assigned to pelacarsen or placebo, and neither they nor their doctors knew who got which2. The trial started in December 2019 and finished collecting its main data in July 2026; each person’s main outcome was tracked over about four years3.
The main goal was to cut the risk of four kinds of serious events taken together: death from heart disease, a heart attack that was not fatal, a stroke that was not fatal, and an urgent artery-opening procedure that needed a hospital stay2. That goal was checked in two groups: everyone with Lp(a) of at least 70 mg/dL, and a smaller group with Lp(a) of at least 90 mg/dL2. People in the trial were already getting standard care, including cholesterol-lowering and blood-pressure drugs2.
Pelacarsen is an antisense drug, a short strand of genetic material built to block the liver’s instructions for making apolipoprotein(a), the extra protein that turns an ordinary cholesterol particle into Lp(a)12.
The evidence so far
The public evidence is still thin. Novartis’s announcement says lower Lp(a) levels “were achieved” with the drug, and gives no event counts2. The trial registry lists the study as completed, with no results posted yet3. The National Lipid Association, a group of cholesterol specialists, noted that the full results are not yet available “but may yield further insight into treatment effect”4.
Novartis’s chief medical officer, Shreeram Aradhye, described what the company has concluded so far:
“Although lower Lp(a) levels were observed with pelacarsen, the findings did not demonstrate that this translated into reduced cardiovascular risk in the overall study population. These are not the results we hoped for, but they provide important evidence that advances scientific understanding of the relationship between Lp(a) lowering and cardiovascular outcomes and may help inform future approaches to cardiovascular risk management.”2
What it does not show yet
Missing a main goal is not the same as showing a drug has no effect at all. Cardiologists have warned against firm conclusions before the complete findings are out1. Researchers want to know whether the drug changed any single type of event, such as heart attacks or the need for artery-opening procedures1. Because the main goal lumps several events together, a treatment could affect some of them without the overall drop being large enough to meet the study’s statistical target1.
The results for the group with the highest Lp(a) levels, 90 mg/dL or more, have also not been described in the public summaries2. Dr Parag Joshi, a cardiologist at UT Southwestern Medical Center and an investigator in the study, said the detailed findings would be important for the future of drugs aimed at Lp(a)1. Specialists are also looking at several possible reasons why the large drop in Lp(a) did not bring the expected benefit, including questions about dosing1.
Why this particle drew so much interest
Lp(a) is made by the liver and looks much like LDL, often called bad cholesterol, but carries the extra apolipoprotein(a) protein1. High levels have been linked to coronary artery disease, heart attacks and disease of the aortic valve1. About one in five people worldwide have raised levels, and the share is higher in people of African and South Asian ancestry12. Novartis says nearly one-third of people who develop heart disease early have high Lp(a)2.
Unlike LDL, Lp(a) is not much changed by diet, exercise or weight loss1. Novartis says levels are about 90 per cent determined by genes2. Doctors can measure it with a blood test, but there is no approved drug aimed at it12.
The sources frame the central question differently. Novartis’s announcement calls high Lp(a) a “causal” risk factor for heart disease2. Coverage of the result says the failure has renewed debate over whether lowering Lp(a) itself brings meaningful heart benefits, or whether the particle mainly signals inherited heart risk1. Novartis framed the trial as a test of whether lowering Lp(a) cuts the risk that remains when other major risk factors are already being treated2.
Who is behind it
Novartis sponsored and ran the trial3. Ionis Pharmaceuticals created the drug, and Novartis holds global rights to develop and sell it under a license and collaboration deal with Ionis2. All the trial results described so far come from Novartis’s own announcement; no independent analysis of the data has been published24.
The National Lipid Association said Lp(a) remains an important and independent risk factor for artery disease, and pointed to its 2024 statement and a 2026 joint guideline from US heart societies that recommend Lp(a) testing in all adults4. The group said people with high Lp(a) should have their other heart risk factors managed intensively4.
Other drugs still in testing
Pelacarsen’s trial is the first of several large studies testing whether lowering Lp(a) cuts heart events4. The National Lipid Association listed others now under way4:
- Eli Lilly’s lepodisiran, an injected RNA-silencing drug, in people with artery disease or at higher risk of it4.
- Amgen’s olpasiran, also an injected RNA-silencing drug, in two trials: one in people who already have coronary artery disease, and one testing whether it can prevent a first heart event in high-risk people4.
- Eli Lilly’s muvalaplin, a pill that disrupts how the Lp(a) particle is put together, in people who have had a heart or artery event or are at high risk4.
These drugs work in different ways and are being tested in somewhat different groups of people, so pelacarsen’s result does not settle how they will do4.
What to watch next
The next step is the full presentation at the American Heart Association meeting in Chicago1. Key details to look for: how many events happened in each group, whether any single type of event fell, how the people with the highest Lp(a) fared, and the drug’s side effects. After that, attention turns to the Lilly and Amgen trials, which will show whether other ways of lowering Lp(a) lead to different outcomes4.
