On September 5, 2026, Reuters reported that pelacarsen, an experimental drug from Novartis AG (NYSE:NVS) and partner Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) meant to lower a cholesterol-carrying particle called Lp(a), failed to reduce heart attacks, strokes and related cardiovascular events in the Lp(a)HORIZON trial, which enrolled more than 8,000 patients.
The drug did lower Lp(a) levels as expected, but that reduction did not translate into fewer real-world cardiac events. Novartis shares fell 5%, and Ionis shares fell 12% in aftermarket trading. Novartis called the results a disappointment but said they still advance scientific understanding of the Lp(a) pathway.
Bull Case
Novartis AG (NYSE:NVS) still has important pipeline opportunities beyond pelacarsen. The failure removes one potential blockbuster. But remibrutinib recently succeeded in a late-stage multiple sclerosis trial and could generate up to $9 billion in peak annual sales if approved. Novartis is also developing other late-stage medicines. It gives the company multiple opportunities to replace revenue as older drugs face patent pressure.
The pelacarsen result does not eliminate the commercial opportunity in Lp(a). Pelacarsen successfully lowered Lp(a), but it failed to reduce heart attacks and strokes in the Phase III trial. Lp(a) affects about 20% of people worldwide, and no approved drug specifically targets it. It leaves a large unmet need for companies that can eventually prove that deeper Lp(a) reduction improves cardiovascular outcomes.
Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) has built a business that goes beyond pelacarsen. Ionis discovered pelacarsen and conducted its early development. However, Novartis holds the rights to develop and commercialize the drug for cardiovascular disease. So Ionis retains its broader pipeline and commercial operations even after the setback, while the firm’s recent approval of Zanvastro for Alexander disease provides another commercial product and validates its focus on RNA-targeted medicines.
Bear Case
Pelacarsen’s failure removes a major potential growth driver for both companies. The six-year study enrolled more than 8,000 patients and showed that pelacarsen lowered Lp(a). Yet the drug failed to reduce major cardiovascular events. Hence, the result weakens the investment thesis behind one of Novartis’ most closely watched pipeline assets and raises the burden of proof for other Lp(a) drugs.
Novartis AG (NYSE:NVS) now faces greater pressure to replace revenue as Entresto and other products approach patent challenges. Investors had identified pelacarsen, remibrutinib, and del-desiran as three key potential growth drivers with combined peak annual sales of more than $10 billion. Losing pelacarsen makes the remaining pipeline more important as Novartis manages one of its most significant periods of patent expirations.
Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) faces greater concentration risk because pelacarsen matters more to the smaller company. Ionis shares fell about 12% after the result, compared with a roughly 5% decline for Novartis. It shows the market assigned greater importance to the drug relative to Ionis’ overall value. This setback also casts doubt on the company’s ability to turn promising RNA medicines into successful cardiovascular products, especially after another late-stage cardiovascular candidate, eplontersen, missed its primary endpoint.
Hedge Fund Sentiment
Hedge fund interest in Novartis AG (NYSE:NVS) actually grew heading into the pelacarsen trial failure, with 38 funds holding a stake at the end of the second quarter versus 31 in the first, and the combined position value rising to $3.66 billion from $3.02 billion. Ionis Pharmaceuticals, Inc. (NASDAQ:IONS) saw the opposite trend, with holders slipping to 54 from 60, even though position value ticked up to $1.74 billion from $1.68 billion. Amgen, whose competing Lp(a) drug olpasiran was also caught up in the market’s reaction, saw its hedge fund position value nearly double to $3.14 billion from $1.63 billion, with holder count little changed at 66.
Conclusion
Pelacarsen’s failure removes a potentially multibillion-dollar growth opportunity and puts greater pressure on Novartis to deliver from its remaining pipeline as Entresto faces patent pressure. Ionis faces a more concentrated impact because pelacarsen carried greater importance relative to its smaller business, even though its broader RNA portfolio and newly approved Zanvastro provide some diversification.
The Lp(a) market remains attractive, but investors now need to see whether rival therapies can prove that deeper Lp(a) reduction actually prevents cardiovascular events and whether Novartis and Ionis can replace the growth they expected from pelacarsen.
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