Novartis' pelacarsen misses primary endpoint in Lp(a)HORIZON Phase III cardiovascular outcomes trial
核心洞察
The Phase III Lp(a)HORIZON trial of pelacarsen did not meet its primary endpoint of reducing the composite risk of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization compared to placebo.
Pelacarsen substantially lowered lipoprotein(a) levels in the study population, which was already receiving guideline-directed lipid-lowering and antihypertensive therapies, but this did not translate into reduced cardiovascular risk.
Elevated Lp(a) is an inherited cardiovascular risk factor affecting approximately one in five people worldwide, with no approved targeted treatment currently available.
Novartis announced on September 4, 2026 that the pelacarsen Phase III Lp(a)HORIZON trial, a pioneering cardiovascular outcomes study, did not meet its primary endpoint of reducing the risk of cardiovascular events compared to placebo. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization. Lower lipoprotein(a), Lp(a), levels were achieved with pelacarsen in the study population, which was receiving guideline-directed treatments including lipid-lowering and antihypertensive therapies.
"Lp(a)HORIZON was a pioneering cardiovascular outcomes trial designed to answer one of the most important unanswered questions in cardiovascular medicine by evaluating whether lowering Lp(a) can reduce residual cardiovascular risk beyond optimized, guideline-directed care, when other major cardiovascular risk factors are already being managed," said Shreeram Aradhye, President, Development and Chief Medical Officer, Novartis. "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. These are not the results we hoped for, but they provide important evidence that advances scientific understanding of the relationship between Lp(a) lowering and cardiovascular outcomes and may help inform future approaches to cardiovascular risk management."
Brett P. Monia, PhD, chief executive officer of Ionis, added: "Although pelacarsen substantially lowered Lp(a) levels consistent with previous studies, we are disappointed that this did not translate to cardiovascular risk reduction. Lp(a)HORIZON was the first pivotal Phase 3 trial to address the question as to whether lowering Lp(a) could reduce cardiovascular risk in people with established cardiovascular disease (搜索) who are already receiving optimal cardiovascular care."
Trial Design and Results
Lp(a)HORIZON (NCT04023552) is a Phase III, randomized, placebo-controlled, double-blind, parallel-group, multi-center global cardiovascular outcomes trial evaluating the effect of pelacarsen on the incidence of 4-point major adverse cardiovascular events (MACE) in 8,323 patients with elevated Lp(a) and established cardiovascular disease (搜索). The primary endpoint was evaluated in the overall population (Lp(a) ≥70 mg/dL) and a subpopulation (Lp(a) ≥90 mg/dL). Pelacarsen demonstrated an acceptable safety profile, and the full Lp(a)HORIZON data will be presented at an upcoming medical congress.
About Pelacarsen
Pelacarsen is an investigational antisense oligonucleotide (ASO) designed to potently inhibit lipoprotein(a), Lp(a), production at its source. Ionis discovered and conducted the early development of pelacarsen. In February 2019, Novartis exercised an option to license the rights to develop and commercialize pelacarsen for targeted cardiovascular therapy, and Novartis obtained global rights to develop, manufacture and commercialize pelacarsen under a license and collaboration agreement with Ionis Pharmaceuticals (搜索).
The Clinical Significance of Elevated Lp(a)
Elevated Lp(a) is an inherited, independent and causal cardiovascular disease (搜索) (CVD) risk factor. Lp(a) levels are approximately 90% genetically determined and largely unaffected by diet or lifestyle. Lp(a) can contribute to plaque buildup and inflammation in the arteries, which can lead to plaque rupture and cardiovascular events. Approximately 20 percent of people worldwide, and nearly one-third of those with premature cardiovascular disease, have elevated Lp(a). US and European guidelines recommend Lp(a) testing once in a lifetime for all adults.
Despite the significant disease burden, there is currently no approved targeted treatment for elevated Lp(a). The Lp(a)HORIZON results therefore provide important new evidence on the relationship between Lp(a) lowering and cardiovascular outcomes, even as the trial did not achieve its primary endpoint. Novartis thanked the more than 8,000 trial participants and investigators who made the study possible and reaffirmed its commitment to driving cardiovascular innovation.