Novartis Cholesterol Trial Setback Casts Shadow Over Multi-Billion Dollar Drug Race

Shares of Novartis dropped 3% on Monday after the company announced a significant clinical setback for pelacarsen, a drug developed in partnership with Ionis Pharmaceuticals. The failure in a high-profile cardiovascular trial has intensified scrutiny of one of the pharmaceutical industry’s most lucrative drug races, which includes competing candidates from Amgen and Eli Lilly.

While pelacarsen successfully reduced lipoprotein(a)—a particularly harmful form of cholesterol linked to elevated cardiovascular risk—it failed to demonstrate a statistically significant improvement in patient outcomes, according to data released after market close on Friday.

This marks the first major clinical hurdle in the pursuit of therapies targeting Lp(a), a genetic condition affecting approximately one in five people worldwide and currently lacking approved targeted treatments. Despite lowering the cholesterol level, the trial did not show enough benefit to prevent heart attacks or strokes.

Analysts at Citi noted that while the “Lp(a) hypothesis is weakened, it is not disproven.” In a research note, they highlighted that critical details remain scarce, including the precise magnitude of Lp(a) reduction achieved by pelacarsen. Further data is required to determine whether the miss stems from the drug’s mechanism, trial design, or a fundamental challenge to the idea that lowering Lp(a) reduces cardiovascular events.

Novartis stated that full results would be presented at an upcoming medical congress. Shreeram Aradhye, the company’s chief medical officer, described the findings as important evidence advancing scientific understanding of the relationship between Lp(a) lowering and cardiovascular outcomes.

The implications extend beyond Novartis. Shares of Amgen fell approximately 5% in extended trading, while Ionis Pharmaceuticals sank 10%. U.S.-listed NewAmsterdam Pharma, which is also developing an Lp(a) treatment, saw its shares drop 12%. Analysts had previously modeled peak annual sales for pelacarsen at between $4 billion and $5 billion, a figure that would have been crucial for Novartis as it navigates what CEO Vas Narasimhan calls the steepest patent cliff in the company’s history, following the loss of key exclusivities for its blockbuster heart drug Entresto.

Jefferies analysts suggested that improving standards of care may be reducing baseline cardiovascular events, potentially making it more difficult and costly for experimental drugs to prove added benefit. However, William Blair analysts argued that because other candidates use different mechanisms to lower Lp(a), they may still achieve deeper reductions, leaving room for success in patients with very high baseline levels.

Citi analysts indicated that Amgen’s olpasiran faces the clearest path to read-through, while Lilly’s lepodisiran is being tested in a broader population, potentially limiting the direct impact of Novartis’ failure on its valuation.