Novartis Lp(a)HORIZON trial fails to show pelacarsen reduces cardiovascular events

Basel, September 4, 2026, Novartis announced today the results of its Phase III Lp(a)HORIZON trial, which aimed to assess the efficacy of pelacarsen in reducing cardiovascular events among patients with elevated lipoprotein (a), or Lp(a), and established cardiovascular disease (CVD). The trial did not meet its primary endpoint of lowering 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 a placebo.

Despite achieving lower Lp(a) levels, pelacarsen did not demonstrate a reduction in overall cardiovascular risk among the study participants. The findings, though disappointing, provide important new insights into the relationship between Lp(a) levels and cardiovascular outcomes. Lp(a) is an inherited cardiovascular risk factor that affects approximately one in five people worldwide and has no approved targeted treatments.

Shreeram Aradhye, President of Development and Chief Medical Officer at Novartis, commented, "Lp(a)HORIZON was designed to address one of the most important unanswered questions in cardiovascular medicine by evaluating whether lowering Lp(a) could reduce residual cardiovascular risk beyond optimized, guideline-directed care. Although the trial showed lower Lp(a) levels with pelacarsen, the results did not translate into a reduction in cardiovascular events in the overall study population. These results, while not what we hoped for, provide crucial evidence that can advance our understanding of Lp(a) and its relationship with cardiovascular outcomes."

The Lp(a)HORIZON trial enrolled 8,323 patients with elevated Lp(a) and established CVD, with the primary endpoint being a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization. The study was conducted in multiple centers globally and was designed to evaluate the impact of pelacarsen on major adverse cardiovascular events (MACE) in both the overall population and a subpopulation with higher Lp(a) levels.

Elevated Lp(a) is an inherited, independent, and causal cardiovascular disease risk factor, with levels largely determined by genetics and only minimally influenced by lifestyle changes. Approximately 20 percent of people worldwide and nearly one-third of those with premature cardiovascular disease have elevated Lp(a).

Novartis' pelacarsen is an investigational antisense oligonucleotide (ASO) designed to inhibit Lp(a) production at its source. The company obtained global rights to develop, manufacture, and commercialize pelacarsen under a license and collaboration agreement with Ionis Pharmaceuticals.

The results of the Lp(a)HORIZON trial will be presented at an upcoming medical congress, and the company remains committed to driving cardiovascular innovation and exploring future approaches to managing cardiovascular risk.

"These findings will be shared at a medical congress to foster scientific dialogue and collaboration," said Aradhye. "We remain committed to exploring new treatment options for individuals with elevated Lp(a) and hope these results will inform future research and clinical strategies."

The company also stated that it will continue to evaluate the potential of pelacarsen in other clinical settings and for different patient populations.