Novartis announced that pelacarsen, an experimental drug developed in partnership with Ionis Pharmaceuticals, did not meet its primary goal in a Phase 3 trial. The drug, intended to reduce major adverse cardiovascular events (MACE) in patients with elevated lipoprotein(a) (Lp(a)), failed to show a significant reduction in heart attacks, strokes, and cardiovascular deaths compared to a placebo. While pelacarsen successfully lowered Lp(a) levels, this reduction did not translate into improved clinical outcomes. This setback led to a substantial decline in Novartis's stock, which fell more than 7% in after-hours trading, and Ionis Pharmaceuticals' shares, which dropped 12%.
The trial results have significant implications for the broader field of Lp(a)-lowering therapies. Pelacarsen was considered a bellwether for this new approach to cardiovascular disease prevention, and its failure raises questions about whether lowering Lp(a) directly leads to fewer cardiovascular events. Analysts, including Citi's Geoffrey Meacham, noted that the outcome "increases uncertainty across the Lp(a) field" but cautioned against declaring the mechanism entirely ineffective, emphasizing the need for full trial data to understand the reasons behind the failure.
Novartis had high hopes for pelacarsen, at one point projecting the Lp(a) drug market could be worth over $5 billion, with UBS analysts estimating peak annual sales for pelacarsen at about $1.5 billion. The failure is a blow to Novartis's efforts to replenish its drug pipeline, especially as it faces significant patent expirations for other key drugs like Entresto. Other companies, such as Amgen and Eli Lilly, are also developing Lp(a)-lowering drugs, and Amgen's stock also saw a nearly 7% decline in post-market trading following the news.
Despite the disappointing results for pelacarsen, Novartis remains committed to cardiovascular innovation. The company's chief medical officer, Shreeram Aradhye, stated that while the results were not what they hoped for, they provide important scientific evidence regarding the relationship between Lp(a) lowering and cardiovascular outcomes. Investors are now focusing on other pipeline drugs, such as remibrutinib and del-desiran, which together with pelacarsen, were projected to generate over $10 billion in peak annual sales. Remibrutinib, however, recently showed positive results in a multiple sclerosis trial, with analysts expecting up to $9 billion in peak annual sales for that drug alone.
