A late-stage trial failure for a closely watched heart drug from Ionis Pharmaceuticals and Novartis is fueling doubts about whether rival therapies built on the same idea will succeed.
Ionis discovered the drug, pelacarsen, and partnered with Novartis in 2019 to develop it. Novartis disclosed in September that the once-monthly injection had failed its Phase 3 trial, and over the weekend a medical journal published the full findings. The detailed data showed that pelacarsen did not reduce the risk of major adverse cardiovascular events, such as heart attacks and strokes, after about five years, even though it did lower levels of lipoprotein(a), or Lp(a).
Novartis will no longer develop the drug, according to Bloomberg.
Investors reacted sharply. Ionis shares plunged 17.8% in premarket trading on Monday, a move driven by the trial data as well as the company's third-quarter results, which included reduced sales guidance for Tryngolza, another heart drug. Swiss-listed shares of Novartis were up about 1%.
Pelacarsen is an antisense oligonucleotide, a type of drug that blocks the production of certain proteins that can damage the heart. In the trial, known as Horizon, it reduced Lp(a), a substance similar to so-called bad cholesterol, except that it is inherited. Neither changes in diet nor statins can lower Lp(a), and scientists had believed that bringing those levels down would translate into fewer serious cardiac events. In 2025, one researcher described targeting Lp(a) as "the next frontier in cardiovascular disease."
The failure now hangs over other drugmakers pursuing Lp(a)-lowering treatments. Eli Lilly's lepodisiran and Amgen's olpasiran are both in Phase 3 studies, and analysts have projected that olpasiran could generate $2.3 billion in peak sales by 2036.
"The data from the HORIZON [trial] call the trial designs of other LP(a) focused programs like Amgen's olpasiran and Lilly's lepodisiran into question," BMO Capital Markets analyst Evan David Seigerman told investors on Sunday. "Given what we saw today, we think the probability of either of their programs demonstrating a clear benefit in secondary prevention in patient populations with well-controlled LDL-C is extremely low."
Ionis stock is now trading at its lowest level of the year. Shares closed at $38.80 on Thursday, well below the year-to-date high of $86.50 reached on Feb. 6.
