Novartis' pelacarsen fails Phase 3, casting doubt on Lp(a) lowering strategy

Novartis announced that its antisense drug pelacarsen failed to meet the primary endpoint in the Phase 3 Lp(a)HORIZON trial.

The study was intended to determine whether the drug’s ability to lower lipoprotein(a) levels would translate into reduced cardiovascular events such as death, non‑fatal myocardial infarction, stroke, or other outcomes. Earlier mid‑stage data had shown up to an 80% reduction in Lp(a) versus placebo, but the late‑stage trial showed no significant benefit on these clinical endpoints.

Analysts described the outcome as a meaningful setback for the broader biotech sector, which has been pursuing Lp(a) reduction as a strategy for cardiovascular risk mitigation, including programs at Eli Lilly and Amgen.

Pelacarsen is being developed in collaboration with Ionis Pharmaceuticals under an August 2023 agreement, and the negative readout may prompt a reassessment of Lp(a) as a therapeutic target.