Novartis disclosed that pelacarsen failed to meet endpoints in a pivotal Phase 3 outcome trial, a major setback for the company’s Lp(a)-lowering strategy in preventing cardiovascular events. In the HORIZON study, the antisense therapy did not reduce cardiovascular death or emergencies such as heart attacks or stroke versus placebo. The failure sharpens scrutiny on whether Lp(a) reduction translates into hard clinical outcomes, despite earlier trials showing large reductions in Lp(a) biomarkers. Novartis will now reassess its cardiovascular pipeline priorities and future study designs.