Novartis’s Lp(a) drug sharply lowered the biomarker but did not prevent cardiovascular events

At the American Heart Association’s 2026 Scientific Sessions, detailed results from Novartis and Ionis’s Phase 3 Lp(a)HORIZON trial confirmed that pelacarsen did not reduce major cardiovascular events in patients with established cardiovascular disease and elevated Lp(a).

Pelacarsen lowered Lp(a) by about 78%, but after a median 4.7 years the primary outcome occurred in 12.3% of participants receiving the drug and 12.1% receiving placebo. Results were similarly neutral among patients with especially high baseline Lp(a).

The findings have prompted Novartis to discontinue pelacarsen’s atherosclerotic cardiovascular disease development program and raise questions about whether lowering Lp(a) will translate into fewer heart attacks and strokes.

Amgen’s olpasiran and Eli Lilly’s lepodisiran are different Lp(a)-lowering medicines with cardiovascular outcomes trials underway. The pelacarsen result raises uncertainty, but does not establish that those drugs will also fail; their trial results are still needed.

Researchers have cautioned that one trial is not definitive evidence against Lp(a) as a treatment target. Differences in drug, patient population, degree and duration of lowering, and trial design may matter.