Novartis Abandons Pelacarsen After Phase 3 Trial Shows No Benefit Over Placebo, Dashing Blockbuster Hopes

Novartis is abandoning pelacarsen, an experimental heart drug developed with Ionis Pharmaceuticals, after the drug failed its pivotal late-stage clinical trial. The Phase 3 Lp(a)HORIZON study found that pelacarsen, despite substantially lowering levels of lipoprotein(a), a cholesterol-carrying particle long suspected of elevating cardiovascular risk, did not reduce the rate of major cardiovascular events compared to a placebo. The composite primary endpoint covered cardiovascular death, non-fatal heart attack, non-fatal stroke, and urgent coronary revascularization requiring hospitalization.

The result was described as stunning by industry observers, because pelacarsen had been considered a potential blockbuster by analysts and represented one of the highest-profile bets on the lipoprotein(a) hypothesis in cardiology. Ionis CEO Brett Monia said the company was "disappointed that this did not translate to cardiovascular risk reduction." Shares of Ionis fell roughly 6% in after-hours trading following the initial disclosure.

The failure landed alongside a parallel setback for Novo Nordisk, whose experimental anti-inflammatory heart drug ziltivekimab also failed to reduce major adverse cardiovascular events in its Phase 3 ZEUS trial, which enrolled more than 6,300 patients. Full data for both drugs were presented publicly on Saturday, and cardiologists and researchers were left questioning whether the studies were flawed in their design or whether foundational assumptions about heart disease pathways need to be revisited. Novo Nordisk said the ziltivekimab result would not affect its adjusted operating profit outlook for 2026 but would trigger a non-cash impairment charge in the third quarter.