Novartis has announced that the pelacarsen phase 3 Lp(a)HORIZON trial, a cardiovascular outcomes study, did not meet its primary endpoint of reducing the risk of cardiovascular events, a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularisation requiring hospitalisation, compared to placebo.

Lower lipoprotein (a), Lp(a), levels were achieved with pelacarsen in this study population, which was receiving guideline-directed treatments, including lipid lowering and antihypertensive therapies. The findings provide important new evidence on the relationship between Lp(a) lowering and cardiovascular outcomes. Elevated Lp(a) is an inherited cardiovascular risk factor affecting approximately 1 in 5 people worldwide with no approved targeted treatment.

Shreeram Aradhye, President, Development and Chief Medical Officer (CMO), Novartis, said, "Lp(a)HORIZON was a pioneering cardiovascular outcomes trial designed to answer one of the most important unanswered questions in cardiovascular medicine by evaluating whether lowering Lp(a) can reduce residual cardiovascular risk beyond optimised, guideline-directed care, when other major cardiovascular risk factors are already being managed.

“Although lower Lp(a) levels were observed with pelacarsen, the findings did not demonstrate that this translated into reduced cardiovascular risk in the overall study population. These are not the results we hoped for, but they provide important evidence that advances scientific understanding of the relationship between Lp(a) lowering and cardiovascular outcomes and may help inform future approaches to cardiovascular risk management. We thank the more than 8,000 trial participants and investigators who made this study possible, and remain committed to driving cardiovascular innovation," Aradhye added.

The Lp(a)HORIZON trial data will be presented at an upcoming medical congress.

Pelacarsen is an investigational antisense oligonucleotide (ASO) designed to potently inhibit lipoprotein (a), Lp(a), production at its source.

Novartis obtained global rights to develop, manufacture and commercialise pelacarsen under a license and collaboration agreement with Ionis Pharmaceuticals.