Novartis’ failure in a closely watched cardiovascular trial has cast a shadow over one of the pharmaceutical industry’s most anticipated drug races, hitting shares of rivals Amgen and Eli Lilly as analysts reassess the potential of a new class of cholesterol treatments.
The Swiss drugmaker said after the bell on Friday that pelacarsen, developed with Ionis Pharmaceuticals, successfully reduced a particularly harmful form of cholesterol in a late-stage trial but failed to significantly improve cardiovascular outcomes. Novartis shares fell 3% on Monday, while Amgen dropped about 5% in extended trading on Friday and Ionis sank 10%. U.S.-listed shares of NewAmsterdam Pharma, another Lp(a) developer, fell 12% in extended trading Friday.
The setback is the first major clinical failure in the race to develop drugs that lower lipoprotein(a), or Lp(a), a genetically determined cholesterol subtype linked to elevated cardiovascular risk. Lp(a) affects roughly one in five people worldwide, and no approved treatment specifically targets it.
Pelacarsen is an antisense oligonucleotide, while Amgen’s olpasiran and Eli Lilly’s lepodisiran use different technologies—small interfering RNA and a novel silencing approach, respectively. All three have shown deep Lp(a) reductions in earlier studies, but pelacarsen’s miss raises questions about whether lowering Lp(a) actually translates into fewer heart attacks and strokes.
“The Lp(a) hypothesis is weakened, but not disproven,” Citi analysts said in a research note, emphasizing that details beyond the topline miss remain scarce, including the size of the Lp(a) reduction achieved. They said more data is needed to determine whether the failure reflects pelacarsen’s specific mechanism, the trial’s design, or a fundamental challenge to the entire approach.
Pressure builds on later studies
Citi analysts said 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.”
Amgen’s olpasiran faces the clearest read-through, given its similar patient population. Lilly’s lepodisiran is being tested in a broader group, including patients without established cardiovascular disease, which could limit direct comparisons, the analysts noted. They also said lepodisiran is less material to Lilly’s overall valuation.
Analysts at Jefferies pointed to improving standards of care as a possible factor in the miss. Novartis emphasized that the more than 8,000 patients in the trial were already receiving optimized treatment. Better background therapy is reducing cardiovascular events in the general population, making it harder and more expensive for experimental drugs to prove an added benefit, Jefferies said in a Sunday note.
Novartis said full results would be presented at an upcoming medical congress. The company’s chief medical officer, Shreeram Aradhye, said the data “provide important evidence that advances scientific understanding of the relationship between Lp(a) lowering and cardiovascular outcomes.”
High hopes, big stakes
Analysts had modeled peak annual sales of $4 billion to $5 billion for pelacarsen if it proved successful, a potential boost for Novartis as CEO Vas Narasimhan has described the steepest patent cliff in the company’s history. Its top-selling heart drug Entresto has already lost key patent exclusivities, and more blockbusters will face generic competition soon.
Investor expectations had tempered the immediate fallout—Novartis fell just 3% in extended trading on Friday—because many already viewed the trial as risky. “The market was expecting a moderate benefit, if not transformational blue-sky result,” Barclays said, adding that Novartis had said even a 13% benefit would have been statistically significant. “Reading between the lines of the release, pelacarsen appears to have fallen materially short of this threshold.”
Novartis did not immediately respond to a request for details on the magnitude of Lp(a) lowering or cardiovascular risk reduction observed.
Lp(a), discovered in 1963, contributes to plaque buildup in arteries and promotes blood clotting. Nearly 50 years after its discovery, researchers found that people with elevated Lp(a) face more than twice the risk of heart attack. Unlike LDL cholesterol, Lp(a) levels are largely determined by genetics and are not significantly changed by diet or exercise.
Because other experimental drugs use different techniques that may produce deeper Lp(a) reductions, some analysts see reason to continue development, especially for patients with very high starting levels. But William Blair analysts said they saw “meaningful risk to a potential future” in Lp(a)-driven cardiovascular trials in light of Novartis’ results.
Source: www.cnbc.com — https://www.cnbc.com/2026/09/08/novartis-cholesterol-setback-drug-race-eli-lilly-amgen.html
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