Novartis and Ionis Heart Drug Pelacarsen Fails Phase 3 Trial, Sending Shares Lower

Pelacarsen, a drug developed by Novartis and partner Ionis Pharmaceuticals to lower lipoprotein(a), or Lp(a), failed to reduce the risk of cardiovascular events in a late-stage clinical trial, the companies announced on Friday. The drug missed the primary endpoint of the Phase 3 HORIZON study, which enrolled 8,325 patients with elevated Lp(a) levels and existing cardiovascular disease.

The failure is a significant blow to a new approach to preventing heart attacks and strokes. Lp(a) is an inherited, cholesterol-carrying particle that simultaneously clogs arteries and promotes blood clots, and no approved therapy currently exists to lower it effectively. Pelacarsen had been widely considered a potential blockbuster, with analysts and investors viewing it as one of Novartis's most important future growth products given the large patient population with elevated Lp(a) and the absence of any competing approved treatments.

Novartis shares fell in after-hours trading following the announcement. The setback is particularly consequential for Novartis, which is navigating a major wave of patent expirations, including growing generic competition for its heart failure drug Entresto. The trial result also raises questions about whether lowering Lp(a) levels alone is sufficient to translate into reduced cardiovascular outcomes, a hypothesis that now faces deeper scrutiny as rival programs from Amgen and Eli Lilly remain in development.