Novartis announced that its Phase III Lp(a)HORIZON trial for pelacarsen did not achieve its primary endpoint, which was to reduce the risk of cardiovascular events. These events included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization, compared to a placebo. While pelacarsen successfully lowered lipoprotein(a) (Lp(a)) levels in patients, this reduction did not translate into a decreased cardiovascular risk for the overall study population. The drug was being evaluated in over 8,000 patients with elevated Lp(a) and established cardiovascular disease.
Pelacarsen, an investigational antisense oligonucleotide (ASO), was developed to inhibit Lp(a) production. Elevated Lp(a) is a genetically determined cardiovascular risk factor affecting about one in five people globally, and currently has no approved targeted treatment. Novartis had acquired global rights to pelacarsen through a licensing agreement with Ionis Pharmaceuticals.
Following the announcement on September 4, 2026, shares of Ionis Pharmaceuticals, Novartis's partner, fell by 6% in aftermarket trading. This trial was a key part of Novartis's long-term growth strategy, as pelacarsen was one of three experimental drugs anticipated to generate more than $10 billion in potential peak annual sales. The results are a disappointment for both companies and raise questions about the future of Lp(a) lowering as a direct strategy for cardiovascular risk reduction.
