Novartis’ pelacarsen failed to reduce cardiovascular risk in the Phase 3 HORIZON trial, dealing a blow to one of the most closely watched attempts to lower Lp(a), a cardiovascular risk factor linked to heart attacks and stroke. The result follows earlier signals that the drug could substantially lower Lp(a) levels. In its update, Novartis said pelacarsen did not achieve a reduction in the risk of major cardiovascular events such as cardiovascular death, heart attack, or stroke compared with placebo. The setback raises new questions about whether Lp(a) lowering alone is sufficient to change hard clinical outcomes across all patient settings. The development also adds urgency for Lp(a) programs that are in late-stage evaluation, as companies and investors recalibrate expectations for the translational link between biomarker modulation and clinical endpoints.