Novartis’ Ionis-partnered antisense pelacarsen failed to reduce cardiovascular death or major events in the Phase 3 HORIZON trial targeting elevated lipoprotein(a) levels. The failure adds to questions about whether Lp(a) reduction alone will translate into clinical benefit. Pelacarsen had shown earlier signals that it could drastically lower Lp(a), but in this late-stage study the company reported no improvement versus placebo on the trial’s primary cardiovascular risk outcomes. The readout is the latest setback for the anti-Lp(a) pipeline and may reshape how sponsors structure next-generation risk-factor programs. For investors and pipeline planners, the trial outcome is likely to affect the pace of late-stage readouts and the threshold for evidence needed to justify further Lp(a) biology bets.