Novartis study of 8,323 patients fails to reduce cardiovascular risk with pelacarsen
Key Facts
Novartis said on September 4, 2026, that the Phase III Lp(a)HORIZON trial of pelacarsen failed to meet its primary objective of reducing the risk of cardiovascular events compared with placebo. The study included 8,323 patients with elevated lipoprotein(a) levels and established cardiovascular disease. The company said protein levels fell among participants who received the drug, but the decline did not demonstrate lower cardiovascular risk across the overall study population. The trial therefore failed to show the clinical benefit it was designed to measure, despite the treatment’s effect on the biomarker. The disclosure announcing the trial’s failure did not confirm that development of the drug would be halted.
The primary endpoint was designed as a composite of four types of events: cardiovascular death, nonfatal myocardial infarction, nonfatal stroke and urgent coronary revascularization requiring hospitalization. The study measured whether pelacarsen reduced the incidence of these events in patients compared with placebo. Novartis said the result did not establish a reduction in risk across all participants, despite lower lipoprotein(a) levels with treatment. The company said patients were receiving guideline-directed therapies, including lipid-lowering drugs and blood pressure treatments. This places the trial’s result in the context of treatment already being received by participants, without changing Novartis’s conclusion that the primary endpoint was not met.
Lp(a)HORIZON was a global, randomized, double-blind, placebo-controlled, multicenter trial measuring pelacarsen’s effect on the incidence of composite major cardiovascular events. According to the official registry, the study began on December 12, 2019, and was completed on July 16, 2026, across 902 sites. It was listed as completed in the registry’s latest published update on August 28, 2026. The registry confirms the study’s completion, but does not in itself establish a decision to end the drug’s development. Novartis had included pelacarsen among its Phase III programs in its second-quarter results presentation published on July 21, 2026, before announcing the HORIZON result in September.
The drug’s development traces back to a license Ionis Pharmaceuticals granted to Novartis in 2019; Ionis says it discovered pelacarsen and designed it to lower lipoprotein(a). The focus on this protein was supported by early results: in an investor presentation dated November 28, 2023, Novartis said Phase II showed dose-dependent reductions in its levels of up to 80%. The Phase III result, however, shifted the test from measuring a reduction in the protein to assessing whether that translated into fewer cardiovascular events in patients. In January 2025, Ionis said Phase III results were expected in the first half of 2026, with regulatory submissions expected in the second half of the year, based on the accumulation of blinded events in the study. The September announcement confirmed the failure of the primary endpoint that those timelines had been leading up to.
Novartis said the study data would be presented at an upcoming medical conference, and its third-quarter results materials identified the American Heart Association’s 2026 Scientific Sessions in November as the venue. The presentation will provide details of the study at the conference, while the company’s announced conclusion remains clear: lowering lipoprotein(a) levels did not demonstrate a reduction in cardiovascular event risk across all participants. In its third-quarter results update, Novartis reiterated that pelacarsen had failed to meet its primary endpoint despite lowering protein levels. Novartis shares closed at $162.55 in the November 6, 2026, session, according to EL7 data. The available evidence does not include the session’s high or low prices, or establish a direct link between the closing price and the study announcement.