Novartis reported Friday that pelacarsen, a late stage hopeful for preventing cardiovascular events, failed to show a benefit on major outcomes compared with placebo. While the drug lowered lipoprotein(a), or Lp(a), it failed to produce a reduction in cardiovascular deaths, heart attacks, or strokes. The company evaluated those events together as MACE. Novartis tested more than 8,000 adults to see if targeting Lp(a) could move the needle on those risks.
"These are not the results we hoped for, but they 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," said Shreeram Aradhye, Novartis' chief medical officer.
Lp(a) has been viewed as a fresh angle in heart disease because millions have elevated levels of this cholesterol-carrying particle. It is largely inherited, so lifestyle changes tend to have little effect. The open question has been whether trimming Lp(a) would actually cut major cardiovascular events in the real world. That is why this Novartis readout was seen as a bellwether while other companies press ahead with similar approaches.
Amgen and Eli Lilly are both developing Lp(a)-lowering medicines, though they remain earlier in their programs.
Wall Street did not expect this outcome. Novartis' US-listed shares slid more than 7% shortly after regular trading ended. The company's American Depositary Receipts had been up 16% for the year through the close. Amgen fell almost 7% in postmarket trading.
Novartis previously projected that the Lp(a) treatment market could top $5 billion. UBS analysts had penciled in around $1.5 billion at peak for pelacarsen, factoring in competition. Novartis licensed the drug from Ionis Pharmaceuticals in 2019.
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Citi's Geoffrey Meacham said Novartis' failure "increases uncertainty across the Lp(a) field." He added he "would not declare the mechanism dead." He also noted the complete readout will be key to sorting out whether the miss stems from the way the drug works, how the trial was run, or a broader challenge to the Lp(a) hypothesis.
Gissette Reyes-Soffer, from Columbia University Irving Medical Center, urged restraint in judging the entire field on a single study, noting that other trials test different drugs and populations. "I remain optimistic," she said.
Novartis plans to present the full results at an upcoming medical meeting. For regular folks weighing future treatments, the takeaway is simple: this one trial didn't deliver on outcomes, but it will be the fine print - and data from other contenders - that shows whether Lp(a) lowering can meaningfully change cardiovascular risk.
