Novartis's pelacarsen cuts Lp(a) 78% but fails to prevent heart attacks
Archived — this story has rotated out of today’s deck. It is kept here in full.
The gist
Novartis's pelacarsen lowered Lp(a) 78.4% but did not reduce heart attacks or strokes in a phase 3 trial.
The miss weakens the case for Lp(a) as a drug target.
Background
Pelacarsen is an injectable drug developed by Novartis, the pharmaceutical company that licensed it from Ionis in 2019, to lower lipoprotein(a), a genetic form of cholesterol that builds plaque in arteries and promotes clotting. About 1 in 5 Americans have high Lp(a), diet and exercise do not affect it, and no approved drug substantially lowers it — which is why cardiologists had high hopes for pelacarsen and other Lp(a)-lowering drugs in late-stage trials. The trial, called Lp(a)HORIZON, tested whether the drug could prevent heart attacks, strokes and other serious heart problems in people with prior heart disease and elevated Lp(a).
How it unfolded
- Mar 2023After a suspected case of anaphylaxis, pelacarsen injections were moved to a medically supervised setting for 6 months before at-home dosing resumed.
- Early Sep 2026Novartis issued a press release announcing pelacarsen had failed to reduce the risk of heart problems and stroke in people with underlying cardiovascular disease.
- Sep 8, 2026Novartis' stock fell 3% after the company said pelacarsen failed to significantly improve cardiovascular outcomes.
- Nov 7, 2026Full Lp(a) HORIZON results were presented at the American Heart Association's Scientific Sessions 2026 in Chicago and published in the New England Journal of Medicine: Lp(a) fell 78.4% with pelacarsen vs 3.2% with placebo at 12 months, but the primary MACE endpoint occurred in 12.3% of the pelacarsen group and 12.1% of the placebo group (HR 1.02; P = .76) over a median 4.7 years.
- Nov 7, 2026Novartis, which had already spent tens of millions of dollars on development, decided to abandon pelacarsen.
Key terms
- phase 3 trial
- A late stage of clinical research testing a treatment's effectiveness in many participants after early safety testing.
- placebo
- A treatment designed to appear real but having no active pharmaceutical effect, used as a comparison in trials.
- MACE endpoint
- A composite measure of major adverse cardiovascular events used as an outcome in heart research.
Source: Wikipedia
Who’s saying what
- Expert
- Steven E. Nissen, senior author of the study, said the drug 'didn't work' — Lp(a) fell 78% but cardiovascular outcomes were unchanged — calling the neutral finding unexpected and surprising to the medical community.
- Expert
- Karol Watson, co-director of the UCLA Program in Preventive Cardiology, said she had not seen a more shockingly neutral trial in a while, but added that the story is 'not over' and is 'kind of just starting.'
- Official
- Novartis said the study 'provides meaningful evidence' about the Lp(a)-heart disease relationship and may help inform future cardiovascular management, even if results were not what it hoped for.
- Analysts
- Citi analysts wrote that 'the Lp(a) hypothesis is weakened, but not disproven.'
Still unverified
Theories offered for why the drug did not work include that therapy was given too late in life to make a difference (average participant age was 60, followed for about five years) and that something about pelacarsen itself may not produce a benefit.