Drug That Lowered Lp(a) Failed to Cut Heart Attacks and Strokes in Major Trial
Novartis reported on September 4, 2026 that its Phase III trial of pelacarsen, a drug designed to lower lipoprotein(a), or Lp(a), did not reduce cardiovascular events in patients who already had elevated levels of the particle and had established heart disease.
Lp(a) is a cholesterol-like particle that diet and exercise barely affect. About 20% of people worldwide carry elevated levels, according to the Novartis release. No drug targeting it is currently approved. The Lp(a)HORIZON trial was the first large randomized test of whether mechanically driving levels down translates into fewer heart attacks, strokes and cardiovascular deaths.
The trial enrolled 8,323 patients with elevated Lp(a) and established cardiovascular disease, per the release. All were on guideline-directed treatments, including lipid-lowering and antihypertensive therapies. Pelacarsen, an investigational antisense oligonucleotide that Novartis licensed from Ionis Pharmaceuticals, did achieve lower Lp(a) levels, but those reductions, Novartis reported, "did not demonstrate that this translated into reduced cardiovascular risk in the overall study population."
The primary endpoint was a four-part composite of cardiovascular death, non-fatal heart attack, non-fatal stroke and urgent coronary revascularization requiring hospitalization. Full data will be presented at an upcoming medical congress, the company said; no hazard ratios or event counts have been released.
Shreeram Aradhye, Novartis' President of Development and Chief Medical Officer, said the trial was "designed to answer one of the most important unanswered questions in cardiovascular medicine" and that the results, while not what the company had hoped for, "provide important evidence that advances scientific understanding of the relationship between Lp(a) lowering and cardiovascular outcomes."
Lp(a) levels are approximately 90% genetically determined, per the release — a fact that has driven decades of interest in a drug that could address what statins and other therapies leave behind.
