Novartis pelacarsen trial fails to reduce heart attacks and strokes despite lowering Lp(a)

Key Points:

• Novartis announced that its experimental drug pelacarsen failed a large clinical trial aimed at reducing heart attacks, strokes, and cardiovascular deaths in patients with elevated lipoprotein(a) [Lp(a)] levels, despite successfully lowering Lp(a) by about 80%.
• Lp(a), a genetic blood particle linked to heart disease risk, affects about one in five people worldwide, and pelacarsen was seen as a potential breakthrough treatment because lifestyle changes do not significantly impact Lp(a) levels.
• The trial involved 8,323 participants with heart disease and high Lp(a), who received either pelacarsen or a placebo via monthly injections over several years, but the drug did not significantly reduce major cardiovascular events compared to placebo.
• The failure challenges the assumption that lowering Lp(a) directly reduces heart disease risk, suggesting Lp(a) may be more of a risk marker than a causal factor, and raises caution for other ongoing Lp(a)-lowering drug trials by companies like Amgen and Eli Lilly.
• This setback follows other recent disappointments in heart disease drug development and highlights the importance of large clinical trials to confirm whether promising treatments actually improve patient outcomes.