Novartis halts pelacarsen development after trial involving 8,323 patients fails
Key Facts
Novartis has halted development of pelacarsen after the Phase III Lp(a)HORIZON trial failed to meet its primary endpoint, according to a company letter dated October 16. The company announced on September 4 that the study had not demonstrated a reduction in the risk of major cardiovascular events compared with placebo. The trial involved 8,323 patients with elevated lipoprotein(a) levels and established cardiovascular disease. The failure ends the program after testing whether lowering this biomarker could reduce residual cardiovascular risk in patients. Novartis said detailed results would be presented at the American Heart Association’s 2026 sessions, while the drug’s future development remained under evaluation in its third-quarter disclosure.
The study set its primary endpoint as reducing the risk of a group of cardiovascular events compared with placebo. The group included cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and urgent coronary revascularization requiring hospitalization. The trial was designed for secondary prevention in patients with elevated lipoprotein(a) levels. Novartis set a threshold of 70 mg/dL or higher for the primary analysis population and 90 mg/dL or higher for the subgroup. These criteria show that the trial involved at-risk patients with existing cardiovascular disease, rather than healthy people being evaluated for primary prevention.
Novartis’s chief medical officer said the study tested whether lowering lipoprotein(a) reduces residual cardiovascular risk on top of optimal guideline-directed care. He added that the results did not show that the biomarker reduction “translated into a reduction in cardiovascular risk in the overall participant population.” The company said participants were receiving guideline-directed treatments, including lipid-lowering therapies and blood pressure control. Pelacarsen nevertheless achieved lower lipoprotein(a) levels in participants. This highlights the difference between affecting the targeted biomarker and demonstrating an effect on the clinical outcome the trial was designed to measure.
Novartis described pelacarsen as an investigational antisense oligonucleotide designed to inhibit the production of lipoprotein(a) at its source. The company said elevated levels of the protein are a genetic risk factor affecting about one in five people worldwide, and that no approved targeted treatment exists. This made lowering the biomarker a key scientific focus of the program, but the study also tested whether that reduction translated into tangible cardiovascular events. The topline results announcement showed that the primary endpoint was not met despite lower protein levels among participants. Novartis’s third-quarter report listed the HORIZON trial as a Phase III secondary prevention study and recorded that it had not met its primary endpoint.
The American Heart Association listed the topline results from the Lp(a)HORIZON trial for a late-breaking science session on Saturday, November 7, from 8:30 to 9:45 a.m. Expanded analyses of the trial were also listed in the same session. Novartis had said in its third-quarter results presentation, published on October 27, that pelacarsen data would be presented at the association’s 2026 sessions. The upcoming presentation will provide access to details of the topline results and expanded trial analyses. The company had said the drug’s future development remained under evaluation.