A phase 3 HORIZON trial has failed to show that pelacarsen reduces cardiovascular death or events compared with placebo in patients enrolled for lipoprotein(a)-lowering, according to Novartis. The result extends uncertainty around Lp(a) biology translating into hard clinical benefit. The trial followed pelacarsen’s earlier ability to reduce Lp(a) levels, setting up a key test for the drug class’s translational premise. With the pivotal endpoint missed, development focus for this approach will likely shift to reassessment of patient selection, target engagement, or trial design. For the broader biotech sector, the failure is a reminder that biomarker lowering does not guarantee event reduction, even with mechanistically compelling targets.