Novartis’ antisense therapy pelacarsen failed to meet clinical endpoints in a Phase 3 outcomes study, dealing another blow to the Lp(a) lowering strategy. The Lp(a)HORIZON study did not reduce the risk of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularization versus placebo. While earlier trials showed pelacarsen could lower lipoprotein(a) levels by up to 80% versus placebo, the absence of cardiovascular benefit raises questions for the broader class of Lp(a) agents seeking outcome validation. Novartis had partnered with Ionis Pharmaceuticals on the asset under an August 2023 agreement. Following the readout, analysts characterized the result as a setback for other dedicated Lp(a) therapies in late-stage development, including siRNA programs from Eli Lilly and Amgen. The failure also amplifies market sensitivity to target-to-outcome translation as more cardiovascular development assets compete for validation.