Novartis said on September 4, 2026, that its experimental heart drug pelacarsen missed the main goal of a large, closely watched trial1. The drug lowered Lp(a), a fat-and-protein particle in the blood that is linked to heart disease, but did not reduce a combined count of serious heart problems compared with placebo (a dummy treatment), the company said1. STAT called it a major blow to Novartis and to efforts to target a common heart disease risk factor2.
Only short company summaries are public so far. The full results have not been released3.
What happened
The trial, called Lp(a)HORIZON, was a Phase 3 study, the last big stage of testing before a drug can be submitted for approval4. It enrolled 8,323 people who already had heart or artery disease and high Lp(a) levels1. People were picked at random to get pelacarsen or placebo, and neither they nor their doctors knew which they got1.
The main goal was a combined measure: the first of four events, namely death from heart disease, a non-fatal heart attack, a non-fatal stroke, or an urgent procedure to reopen heart arteries that needed a hospital stay1. The trial looked at this in everyone with Lp(a) of at least 70 mg/dL, and in a subgroup with at least 90 mg/dL1. Novartis said the trial “did not meet its primary endpoint” for this combined measure compared with placebo1.
Lp(a) levels did come down. Novartis said lower Lp(a) levels were achieved with the drug1, and Ionis, the company that discovered pelacarsen, said the levels fell substantially, consistent with earlier studies5. Ionis also said the drug showed “an acceptable safety profile”5.
“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.”
That is how Shreeram Aradhye, Novartis’s chief medical officer, put it in the company statement1.
Why Lp(a) got so much attention
Lp(a) is about 90% set by genes and largely unaffected by diet or lifestyle, according to the companies1. Roughly one in five people worldwide have high levels, and so do nearly one-third of people with heart disease that starts early1. The companies describe it as a cause of heart disease that can add to plaque and inflammation in the arteries5. There is no approved treatment aimed directly at it1.
Pelacarsen is an antisense drug, a piece of genetic material designed to block the liver from making a key part of the Lp(a) particle3. In the trial plan it was given as a monthly injection under the skin6. Earlier trials had shown it could drastically lower Lp(a)2. The big open question was whether lowering the number on a blood test would also mean fewer heart attacks, strokes and deaths. This trial was built to test that in people already getting standard care, including cholesterol and blood pressure drugs5.
What it does not show yet
Much is still unknown because the full data are not out. The National Lipid Association, a medical society for cholesterol specialists, said the full results “may yield further insight into treatment effect”3. Questions that the public summaries do not answer include:
- How large the gap between drug and placebo was on the combined measure, if there was one.
- Whether any of the four separate events, such as heart attacks or strokes on their own, moved in either direction. The companies reported only the combined measure.
- What happened in the subgroup with the highest Lp(a) levels. Novartis’s wording refers to the “overall study population”1.
- How much Lp(a) fell in this trial, and the details behind the safety description.
Both companies said the full results will be presented at an upcoming medical meeting5.
The result also applies to one group: people who already had heart or artery disease and were on standard treatment5. It does not directly test people with high Lp(a) who have not had heart problems.
Who is behind it
Novartis sponsored and ran the trial4. Ionis discovered pelacarsen and did its early development, and Novartis took a license to develop and sell it in February 20195. The trial started in December 2019 and finished collecting its main data in July 20264. STAT described it as a seven-year study7. When enrollment closed in 2022, the results had been expected in 20256.
Ionis chief executive Brett Monia said the company was “disappointed” and that the results “provide clarity that will meaningfully inform future cardiovascular care”5. All of the result descriptions in this article come from the two companies; no independent group has seen the full data yet.
How it fits the field
Pelacarsen was the first drug of its kind to reach a final heart outcomes trial, and several other companies are spending billions of dollars on their own Lp(a) drugs, STAT reported7. The National Lipid Association listed the other large trials still running3:
- Eli Lilly’s lepodisiran, an injection, in people with artery disease or at higher risk (the ACCLAIM-Lp(a) trial)3.
- Eli Lilly’s muvalaplin, a pill that interferes with how the Lp(a) particle is built (the MOVE-Lp(a) trial)3.
- Amgen’s olpasiran, an injection, in people who already had a heart attack or artery procedure (OCEAN(a)-Outcomes), and in people at high risk who have not yet had a heart event (OCEAN(a)-PreEvent)3.
These drugs work in different ways from pelacarsen and are being tested in partly different groups of people3, so their results cannot be predicted from this one. Still, the news landed hard on the field. A STAT headline said failures by Novartis and Novo Nordisk would likely “pop a hole in the balloon” of the field, and the story’s subhead said an expert expects that after a resurgence in heart drug trials, investment will be harder to come by7. That story features Ethan Weiss, a cardiologist at the University of California, San Francisco and co-founder of the startup Marea Therapeutics7. The rest of the article is behind a paywall, so Biohack could not confirm the exact wording or context of the views it reports.
The National Lipid Association said Lp(a) “remains an important and independent risk factor” and that its 2024 statement and the 2026 US cholesterol guideline still recommend testing Lp(a) in all adults3. It said people with high Lp(a) should have their other heart risk factors managed intensively3.
What to watch next
- The full Lp(a)HORIZON results at a medical meeting, including each of the four outcomes and the high-Lp(a) subgroup5.
- Whether results are later posted to the public trial registry, which did not list any results as of its last record4.
- Readouts from the Lilly and Amgen trials, which will show whether a different drug or a different group of patients gives a different answer3.
For now, the measured facts are limited: a large trial, a drug that lowered a blood marker, and, according to the companies, no reduction in a combined count of serious heart events compared with placebo.
