Novartis AG's shares dropped by 3.3% on Monday after its experimental cholesterol drug, pelacarsen, failed to significantly reduce the risk of heart attacks and strokes in a late-stage study. The drug, which was developed with Ionis Pharmaceuticals and intended to lower lipoprotein(a) or Lp(a) levels, did successfully reduce Lp(a) but did not translate into a statistically significant reduction in major adverse cardiovascular events in the 8,000-patient Lp(a)HORIZON trial. This outcome casts doubt on the broader therapeutic approach of targeting Lp(a) for cardiovascular prevention, especially since patients in the trial were already receiving standard lipid-lowering and antihypertensive treatments.
Analysts had projected pelacarsen to be a potential blockbuster, with peak annual sales estimated between $3 billion and $6 billion. The failure means a significant loss of potential future revenue for Novartis and highlights the substantial investment made in the costly cardiovascular outcomes trial that did not yield a marketable product. This setback also intensifies pressure on other drugs in Novartis's pipeline, including the experimental muscular dystrophy drug del-desiran, which the company acquired for $12 billion and whose trial results are anticipated in the fourth quarter. Success for del-desiran is deemed crucial to justify the acquisition cost.
The market reacted by pushing Novartis's shares down to $159.99, a 1.90% decline from the prior close of $163.09 on September 4, 2026. While not an existential threat to a company of Novartis's scale, which reported $14.41 billion in second-quarter 2026 net sales, the failure does remove a significant growth pillar and increases the pressure for successful outcomes from other late-stage assets. The company's diverse portfolio with strong performers like Kisqali (up 43%), Kesimpta (up 32%), and Leqvio (up 59%) somewhat mitigates the impact, but the pelacarsen disappointment underscores the challenges in developing blockbuster prevention drugs.
This outcome also raises the competitive bar for rival Lp(a)-lowering drugs from Amgen and Eli Lilly, which are currently in late-stage trials. The full data from Novartis's pelacarsen trial will be crucial for understanding whether any specific patient subgroups benefited or if there were varying effects across different cardiovascular events, which could inform future development or a narrower indication. Despite this setback, Novartis's shares had gained approximately a fifth in value earlier in the year, fueled by optimism for its pipeline despite upcoming patent expirations for older drugs.
