Novartis' Lp(a) therapy falls short on key cardiovascular goal
核心洞察
Novartis reported that pelacarsen, developed with Ionis Pharmaceuticals, missed the primary endpoint in the Phase III Lp(a)HORIZON cardiovascular outcomes trial.
The trial enrolled 8,323 patients with elevated Lp(a) (搜索) and established heart disease, all receiving standard guideline-directed heart medications.
Pelacarsen lowered Lp(a) (搜索) levels as designed, but fewer patients than hoped avoided cardiovascular death, heart attack, stroke or urgent artery procedures versus placebo.
Novartis said earlier this month that pelacarsen, an antisense drug it has been developing with Ionis Pharmaceuticals, missed the primary endpoint in the Phase III Lp(a)HORIZON trial. The study enrolled 8,323 patients with elevated Lp(a) (搜索), a genetically inherited cholesterol-like particle, plus established heart disease. Pelacarsen lowered Lp(a) (搜索) levels as intended, but fewer patients than researchers had hoped avoided cardiovascular death, heart attack, stroke or urgent artery procedures compared with placebo, with all participants also on standard heart medications.
Shreeram Aradhye, Novartis President of Development and Chief Medical Officer, said the trial was designed to test whether lowering Lp(a) (搜索) can reduce residual cardiovascular risk beyond optimized, guideline-directed care when other major risk factors are already managed. He said that although lower Lp(a) levels were observed, the findings did not demonstrate that this reduction translated into lower cardiovascular risk across the overall study population. Aradhye said the study provides evidence to advance understanding of the relationship between Lp(a) lowering and cardiovascular outcomes, and thanked the more than 8,000 participants and investigators.
Roughly one in five people carry elevated Lp(a) (搜索), which is almost entirely inherited and barely affected by diet and exercise, and nearly a third of people who develop heart disease young have high levels. Before pelacarsen, no approved drug targeted it directly, which made the trial a test of the underlying risk-factor theory rather than of one drug. Full data will be presented at an upcoming medical congress. Other drugmakers continue to pursue Lp(a) (搜索) through different molecular routes, though the result may slow expectations for an approved Lp(a) therapy.