Novartis's cholesterol drug pelacarsen, developed with Ionis Pharmaceuticals, failed to meet its primary endpoint in the Phase III Lp(a)HORIZON trial. While the drug successfully lowered lipoprotein(a) (Lp(a)) levels, it did not reduce the risk of cardiovascular events like heart attacks and strokes in patients already on standard treatments. This setback led to Novartis shares falling more than 3% and Ionis shares dropping almost 10% in after-hours trading, near the bottom of its 52-week range of $50.01 to $86.74.
Analysts had projected pelacarsen to be a blockbuster, with peak annual sales forecasts ranging from $1.5 billion (UBS) to $6 billion (Jefferies). The trial's failure casts doubt on the entire class of Lp(a)-lowering drugs, including those from Amgen and Eli Lilly, as it questions whether reducing Lp(a) translates to cardiovascular benefits. Jefferies analyst Michael Leuchten suggested this raises skepticism about Lp(a)-lowering therapies' ability to show cardiovascular benefit.
This outcome is particularly impactful for Novartis as it relies on new medicines like pelacarsen to sustain growth amidst patent expirations for older blockbusters, such as Entresto. The company's CEO, Vas Narasimhan, had aimed for 5% to 6% annual sales growth until 2030, a target now under pressure. The focus now shifts to other pipeline assets, including del-desiran, an RNA therapy for a rare muscle disease acquired through the $12 billion purchase of Avidity, and the anti-inflammatory drug remibrutinib, which recently showed success in multiple sclerosis trials.
