Novartis says pelacarsen failed trial involving 8,323 patients
Key Facts
Novartis said on September 4, 2026, that pelacarsen failed to meet the primary endpoint in the Phase III Lp(a)HORIZON trial, as it did not demonstrate a reduction in the risk of cardiovascular events compared with placebo. The composite endpoint included cardiovascular death, nonfatal myocardial infarction and nonfatal stroke, as well as urgent coronary revascularization requiring hospitalization. The group receiving the drug had lower Lp(a) levels, but this did not demonstrate a reduction in risk across all participants. The company said participants were receiving recommended treatments, including lipid-lowering therapy and treatment for high blood pressure. The result puts to the test the relationship between lowering this marker and reducing cardiac events in patients with existing cardiovascular disease.
The trial enrolled 8,323 patients with existing cardiovascular disease and elevated Lp(a) levels in a global, multicenter, randomized, double-blind, placebo-controlled study. The study measured the outcome in the overall group of participants whose Lp(a) level was 70 mg/dL or higher. It also defined a subgroup with levels of 90 mg/dL or higher. Participants were receiving guideline-directed care, including lipid-lowering treatments and antihypertensive drugs. HORIZON therefore tested whether the drug added clinical benefit to existing risk-factor care in this population.
Novartis's statement confirms that Lp(a) was lowered in the group receiving pelacarsen, but describes the primary result across all participants as not achieved. This means that the reduction in the marker in the study was not accompanied by evidence that the clinical objective the trial was designed to measure had been met. In its topline results, the company did not announce that the drug reduced the risks of cardiac death, heart attack, stroke or urgent revascularization. The trial was also conducted on top of the lipid-lowering and blood-pressure treatments patients were already receiving. The medical community is awaiting the detailed results, including extended analyses, at the scientific session scheduled for November.
Novartis's statement describes elevated Lp(a) as a genetic risk factor and estimates that its levels are about 90% genetically determined. The company says elevated levels affect about one in five people worldwide, and that nearly one-third of people with early-onset cardiovascular disease have elevated levels. The American Heart Association recommends that every adult have their Lp(a) checked at least once in their lifetime, and estimates that elevated levels affect about one in five people globally. The association says lifestyle changes do not lower Lp(a) levels, but may help reduce overall cardiac risk by managing blood pressure, diabetes and cholesterol and maintaining physical activity. Novartis says there is no approved targeted treatment for this risk factor, explaining the interest in determining whether lowering it changes clinical outcomes.
HORIZON began in December 2019, and collection of primary-outcome data was completed in July 2026, according to the ClinicalTrials.gov record. The original design estimated enrollment of 7,680 participants, before the actual number reached 8,323 patients. Pelacarsen was tested at a dose of 80 mg injected under the skin monthly against placebo. In competing research, Phase II data announced by Eli Lilly showed that lepodisiran lowered Lp(a) by an average of 93.9% between days 60 and 180 at the highest dose tested, 400 mg. This remains a biomarker result and does not by itself demonstrate a reduction in cardiac events.
In the same study, the average Lp(a) level among those who received two doses of lepodisiran at 400 mg remained 91.0% below baseline on day 360, then 74.2% below baseline on day 540. The Phase II OCEAN(a)-DOSE study also showed that doses of olpasiran of 75 mg or more every 12 weeks lowered Lp(a) by more than 95% compared with placebo at week 36. These results concern reductions in the marker and do not represent cardiac-outcomes trial results. A Reuters report said HORIZON's failure adds to the burden of proof for competing drugs from Amgen and Eli Lilly, noting that their trials are testing patients with particularly high levels. Novartis shares had fallen more than 3% on Monday, September 7, after the trial failure was announced.
The American Heart Association listed the presentation of HORIZON's primary results and an extended-analyses supplement for Saturday, November 7, 2026, from 8:30 to 9:45 a.m. The association's scientific meetings are being held in Chicago from November 6 to 9. The presentation follows the company's announcement that the trial had not met its primary endpoint, while confirming that Lp(a) levels fell among those who received the drug. The session is scheduled to present study details to the medical community, including extended analyses. Attention is focused on what those details will add to the interpretation of the result in patients with higher Lp(a) levels.