Novartis’ antisense therapy pelacarsen failed to demonstrate clinical benefit in its Phase 3 cardiovascular outcomes study, according to the company’s readout. Although prior work showed substantial lipoprotein(a) lowering, the Lp(a)HORIZON trial did not hit its primary endpoint spanning cardiovascular death, non-fatal MI, non-fatal stroke, and urgent revascularization requiring hospitalization. Analysts described the result as a setback for Lp(a)-lowering programs where biomarker reductions had previously driven optimism. The outcome increases the proof burden for other dedicated Lp(a) therapies in late-stage development, including siRNA approaches from Eli Lilly and Amgen. The broader biotech effect is on cardiovascular target validation: pelacarsen’s failure underscores that strong biomarker modulation does not guarantee event reduction, and it may influence partner diligence, trial design scrutiny, and near-term risk tolerance for Lp(a) lowering assets.