After the bell Friday, Novartis said pelacarsen, which it developed with Ionis Pharmaceuticals, reduced a dangerous cholesterol particle during a late‑stage trial but failed to achieve a statistically significant improvement in cardiovascular outcomes. The company plans to present the full results at an upcoming medical congress. Novartis shares were down about 3% in extended trading Friday and fell 3% on Monday, while Amgen slid roughly 5%, Ionis lost 10%, and U.S.‑listed shares of Netherlands‑based NewAmsterdam Pharma declined 12% in Friday's after hours.
This is the first big clinical stumble in the push to treat elevated lipoprotein(a), or Lp(a), which is estimated to raise cardiovascular risk for about one in five people worldwide and currently has no approved therapy that directly targets it. Lp(a) was identified in 1963 and is linked to plaque buildup and clotting; decades later, researchers found people with high Lp(a) faced more than double the risk of a heart attack. Levels are determined predominantly by heredity and, in contrast to LDL cholesterol, respond little to diet or exercise.
Citi analysts summed up the signal this way: "The Lp(a) hypothesis is weakened, but not disproven." They said information is limited beyond the topline miss, including how much pelacarsen actually lowered Lp(a), and that more data are needed to understand whether the outcome reflects the drug's mechanism, the study's design, or a broader challenge to the idea that lowering Lp(a) will reduce heart attacks and strokes. Novartis' chief medical officer, Shreeram Aradhye, said the results "provide important evidence that advances scientific understanding of the relationship between Lp(a) lowering and cardiovascular outcomes and may help inform future approaches to cardiovascular risk management."
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Amgen and Eli Lilly are evaluating distinct platforms that have produced larger drops in Lp(a), but pelacarsen's failure raises the perceived risk in a field many thought could yield billions in revenue. Analysts had penciled in roughly $4 billion to $5 billion in peak annual revenue for pelacarsen if successful, which would have helped Novartis as it navigates what CEO Vas Narasimhan has termed the steepest patent cliff in the company's history. The broader market took notice: in Friday's after-hours session, Amgen declined roughly 5%, while Ionis dropped 10%. U.S.‑listed NewAmsterdam Pharma also slid 12%.
Citi wrote that "the first dedicated outcomes failure lowers confidence across the class and places greater pressure on later studies to demonstrate that deeper lowering can produce a clinically meaningful ~15% [major adverse cardiovascular events] reduction." They said Amgen's olpasiran has the clearest readthrough, while Lilly's lepodisiran is being tested in a broader population, including patients without established cardiovascular disease, which may limit direct comparisons to Novartis' result. They also noted lepodisiran is less material to Lilly's valuation. William Blair analysts said some approaches could still reduce Lp(a) more than pelacarsen, especially in patients starting with very high levels, but they see "meaningful risk to a potential future" in Lp(a) trials after this update.
Novartis noted that over 8,000 participants in the trial were already receiving optimized care. Jefferies analysts emphasized that rising standards of care are cutting the rate of cardiovascular events, making it tougher and costlier for experimental therapies to demonstrate incremental benefit. Many investors had considered the trial high risk and anticipated only a modest success, which may account for the relatively muted reaction in Novartis shares. Barclays put it this way: "The market was expecting a moderate benefit, if not transformational blue‑sky result." They added that "NOVN had noted even a 13% benefit would have been statistically significant in the overall population, and reading between the lines of the release, [pelacarsen] appears to have fallen materially short of this threshold."
For everyday investors, the next milestones are the detailed readout at a medical meeting and how Amgen's and Lilly's programs perform. If deeper Lp(a) lowering translates into fewer heart attacks and strokes, this category could still matter. If not, expectations and valuations tied to Lp(a) will likely reset. Either way, this is a reminder that even big, promising drug ideas have a long road from lab theory to real‑world outcomes.
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