Few concepts in cardiovascular medicine have sparked as much optimism as Lp(a)-lowering medications. That optimism was dashed on September 4 when Novartis AG (NYSE:NVS) revealed that its experimental medication Pelacarsen failed to reduce heart attacks, strokes, and cardiovascular deaths in a major trial. The impact rippled far beyond Novartis. Shares of partner Ionis Pharmaceuticals (NASDAQ:IONS) dropped 10%, and rival Amgen Inc. (NASDAQ:AMGN) dropped as much as 10% on its own, although Amgen’s competing drug has yet to release results.
A Negative First-of-Its-Kind Trial
Pelacarsen, developed with Ionis, accomplished exactly what it was supposed to do at the biomarker level: it reduced Lp(a) levels. However, Novartis reported that this reduction didn’t result in fewer cardiovascular deaths, heart attacks, strokes, or urgent coronary operations than the placebo. It was the first completed outcomes trial to determine if reducing Lp(a) prevents cardiovascular events, and the results were negative.
A Big Hit for Novartis Itself
Novartis’ shares fell more than 3% in Swiss trading following the pelacarsen setback, while Ionis also sold off sharply. Novartis suffered a much larger decline the following day after a separate Phase 3 failure for del-desiran, so that later selloff cannot be attributed solely to pelacarsen. Analysts had predicted peak annual sales of $3-6 billion if the treatment was successful, and CEO Vas Narasimhan has described the company as facing its steepest patent cliff yet, with blockbuster heart drug Entresto already losing important exclusivity rights.
Amgen: A Victim of Pure Read-Through
Amgen does not yet commercialize a Lp(a) medicine; its candidate, olpasiran, is still being studied in the Phase 3 OCEAN(a)-Outcomes trial, and outcome data isn’t yet publicly available. However, Amgen shares fell about 10% on September 8, marking their worst trading day since October 2000, owing to the fact that olpasiran targets the same biological pathway via a comparable RNA-based approach. Wall Street had already priced in significant optimism for the drug: Cantor Fitzgerald assessed that the market was expecting at least a 65% probability that olpasiran would succeed. Novartis’ failure required an immediate downward adjustment of that probability, despite the lack of a single new data point from Amgen’s trial.
Smart Money Sentiment
Institutional positions differed across the three companies prior to this announcement. Novartis saw hedge fund ownership increase from 31 in the first quarter to 38 in the second. Amgen also had a minor growth, from 65 funds to 66. In contrast, Ionis saw hedge fund holdings fall from 60 to 54 over the same period, a decrease that predates the trial failure but coincides with the company suffering one of the sharpest falls on the news itself.
Why Amgen and Novartis Could Still Win
The case for these companies is based on the concept that a single failed trial does not always mean the end of the Lp(a)-lowering medication class. Pelacarsen and olpasiran, while targeting the same biomarker, use different molecular designs, dosing regimens, and patient populations, implying that Amgen’s olpasiran could succeed where pelacarsen failed, especially if trial-specific factors, such as patient selection or dosing, contributed to Novartis’ disappointing results. For Novartis, some of the pelacarsen disappointment may already be reflected in the stock, although the much larger later selloff was also driven by the separate Phase 3 failure of del-desiran.
What If Lowering Lp(a) Just Doesn’t Work?
However, this was the first-ever completed outcomes trial testing the entire Lp(a)-lowering hypothesis, and a negative result raises a fundamental scientific question about whether lowering this specific biomarker actually prevents cardiovascular events, a concern that applies to all drugs in the class, not just Pelacarsen. According to Cantor Fitzgerald, Amgen’s about 65% priced-in probability of success indicates that the market still has legitimate hopes for olpasiran, and any similar disappointment when its own trial results are released might compound the damage rather than reverse it.
Insider Monkey’s Bottom Line
The trial’s failure poses a scientific concern that goes beyond any single company: whether reducing Lp(a) levels has any significant cardiovascular benefit at all. Novartis faces the most immediate financial consequences due to its greater reliance on Pelacarsen during an already challenging patent cliff. Ionis also faces a direct setback because it discovered and conducted the early development of pelacarsen before licensing development and commercialization rights to Novartis. The selloff in Amgen, in the absence of new data, is the best sign of how much this result has changed Wall Street’s perception of the entire drug class, and investors should view the eventual readout of olpasiran’s trial as the next key test, which will either validate the market’s now more negative view of Lp(a)-lowering therapies or offer a reprieve if Amgen’s unique drug design leads to a different result.
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