Novartis’ phase III Lp(a)HORIZON trial has failed to show that pelacarsen can reduce the risk of major cardiovascular events, dealing a setback to efforts to develop the first targeted treatment for elevated lipoprotein(a), or Lp(a).

 

The pivotal cardiovascular outcomes trial did not meet its primary endpoint, which measured a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and urgent coronary revascularization requiring hospitalization, compared with placebo.

 

Pelacarsen did lower Lp(a) levels among participants receiving guideline-directed care, including lipid-lowering and antihypertensive therapies. However, the reduction in Lp(a) did not translate into a lower risk of cardiovascular events in the overall study population.

 

"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 optimized, guideline-directed care, when other major cardiovascular risk factors are already being managed," said Shreeram Aradhye, President, Development and Chief Medical Officer, Novartis. 

 

"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."