Novartis' Pelacarsen Misses Primary Goal in Phase 3 Lp(a)HORIZON Outcomes Trial
The antisense drug lowered lipoprotein(a) but did not reduce major cardiovascular events against placebo in 8,323 patients with established heart disease, the company said.
These results come from a Phase 3 trial, the large trial usually needed before approval.
Key points
- Novartis said on September 4 that pelacarsen did not meet the primary endpoint of the Phase 3 Lp(a)HORIZON trial, a reduction in major adverse cardiovascular events versus placebo.
- Patients on pelacarsen reached lower Lp(a) levels, but that did not translate into reduced cardiovascular risk in the overall study population, according to the company's topline announcement.
- Full data are due at an upcoming medical congress; Novartis did not say whether the result changes its regulatory plans for the drug.
Novartis said on September 4 that its Phase 3 Lp(a)HORIZON trial of pelacarsen did not meet its primary endpoint of reducing cardiovascular events compared with placebo in patients with elevated lipoprotein(a), or Lp(a), and established cardiovascular disease, according to the company's announcement.
The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and urgent coronary revascularization requiring hospitalization. Pelacarsen did lower Lp(a) levels in the trial population, which was also receiving guideline-directed treatments including lipid-lowering and blood pressure drugs, Novartis said. The results are company-reported topline data; detailed figures have not been released.
The trial
Lp(a)HORIZON (NCT04023552) is a randomized, double-blind, placebo-controlled global outcomes trial that enrolled 8,323 patients with elevated Lp(a) and established cardiovascular disease. The primary endpoint was assessed in the overall population, defined as Lp(a) of at least 70 mg/dL, and in a subpopulation with Lp(a) of at least 90 mg/dL.
Pelacarsen is an investigational antisense oligonucleotide designed to block production of Lp(a). Novartis holds global rights to the drug under a license and collaboration agreement with Ionis Pharmaceuticals. In an earlier Phase 2 dose-ranging trial of 286 patients, published in the New England Journal of Medicine in 2020, the drug cut Lp(a) by up to 80% at the 20 mg weekly dose, HCPLive reported.
Elevated Lp(a) is an inherited cardiovascular risk factor that affects about one in five people worldwide and has no approved targeted treatment, according to 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," said Shreeram Aradhye, Novartis' president of development and chief medical officer. "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."
What comes next
Novartis said the Lp(a)HORIZON data will be presented at an upcoming medical congress. The company did not say whether the result will affect the regulatory path for pelacarsen or the design of ongoing Phase 3 substudies, including trials in Black, African American and Hispanic populations and in patients with recent acute coronary syndrome, HCPLive reported.
Other drugs that lower Lp(a), including the small interfering RNA candidates lepodisiran and zerlasiran, remain in development, according to HCPLive.
Sources
- Novartis announces Lp(a)HORIZON Phase III topline results for pelacarsen in patients with elevated Lp(a) and established cardiovascular disease (CVD), Novartis, September 4, 2026
- Pelacarsen Misses Primary Endpoint in Lp(a)HORIZON Phase 3 Trial, HCPLive, September 5, 2026