The drug is pelacarsen, developed by Novartis and Ionis to lower lipoprotein(a), or Lp(a)—an inherited cholesterol-carrying particle linked to cardiovascular risk. In the large Phase 3 Lp(a)HORIZON trial, it did not significantly reduce major cardiovascular events, despite earlier studies showing it could lower Lp(a) substantially.
Why it failed is not yet clear from the reported topline results. Possible explanations include the amount or duration of Lp(a) reduction, the patients enrolled, and the trial’s composite outcome—which included stroke, whose relationship to Lp(a) is less certain. Another possibility is that lowering Lp(a) does not translate into as much risk reduction as researchers hoped, particularly when other risk factors are already treated.
The result weakens—but does not settle—the case for Lp(a) as a treatment target. Amgen’s olpasiran and Eli Lilly’s lepodisiran remain in large outcomes trials, using different approaches and reportedly producing deeper Lp(a) reductions in earlier studies. Their results will help show whether pelacarsen’s miss was specific to its drug or trial, or challenges the broader strategy.
Bottom line:
there is still hope, but the field now needs hard evidence that lowering Lp(a) prevents heart attacks and other events—not just that it lowers the blood measurement. Full trial data are important for understanding the miss.
Sources:
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