Novartis's pelacarsen fails cardiovascular outcomes trial in Phase 3 study
Lp(a)HORIZON did not reduce cardiovascular events despite lowering Lp(a) levels, Ionis and partner Novartis reported.
On September 4, 2026, Ionis Pharmaceuticals disclosed that its partner Novartis reported topline results from the Phase 3 Lp(a)HORIZON trial of pelacarsen. The study did not meet its primary endpoint of reducing the risk of cardiovascular events, a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization, compared to placebo.1
Consistent with previous studies, substantially lower lipoprotein (a) levels were achieved with pelacarsen.1 Pelacarsen demonstrated an acceptable safety profile.1 Full data from Lp(a)HORIZON will be presented at an upcoming medical congress.1
Ionis CEO Brett P. Monia said the company was disappointed the Lp(a) lowering did not translate into reduced cardiovascular risk, and noted Lp(a)HORIZON was the first pivotal Phase 3 trial to test whether lowering Lp(a) could reduce cardiovascular risk in people with established cardiovascular disease already on optimal care, and that while the primary endpoint was missed, the results would meaningfully inform future cardiovascular care, according to the company.1
Ionis discovered and conducted early development of pelacarsen, and in February 2019 Novartis exercised an option to license rights to develop and commercialize the drug for targeted cardiovascular therapy.1
The trial itself was substantial in scope. Lp(a)HORIZON (NCT04023552) was a Phase 3, randomized, placebo-controlled, double-blind, parallel-group, multi-center global cardiovascular outcomes trial evaluating pelacarsen's effect on 4-point MACE in 8,323 patients with elevated Lp(a) and established cardiovascular disease, with the primary endpoint assessed in both an overall population (Lp(a) ≥70 mg/dL) and a subpopulation (Lp(a) ≥90 mg/dL), while participants also received guideline-directed lipid lowering and antihypertensive therapies.1
Ionis noted it continues to commercialize its own medicines TRYNGOLZA, DAWNZERA and now ZANVASTRO, while advancing its broader pipeline, according to the company.1
Written by readthrough’s AI from the linked primary sources and fact-checked against them automatically before publishing. Not investment advice.