A failed trial for a heart drug casts shadow over rivals developing similar therapies

By Jaimy Lee

The full data from the closely watched clinical trial showed that the drug had no cardiovascular benefit even though it reduced Lp(a) levels

The full clinical-trial data for a heart drug from Ionis and Novartis showed that pelacarsen didn't reduce the risk of major cardiovascular events.

A late-stage clinical-trial failure of Ionis Pharmaceuticals and Novartis' highly anticipated heart drug is raising questions about whether similar therapies will work.

Ionis and Novartis teamed up in 2019 to develop pelacarsen, which Ionis discovered. But in September, Novartis revealed that the once-monthly injection failed the Phase 3 trial. And over the weekend, a medical journal published detailed findings that showed pelacarsen didn't lower the risk of major adverse cardiovascular events like heart attacks or strokes after about five years.

Novartis has now stopped work on the drug for patients with atherosclerotic cardiovascular disease, according to a company spokesperson. However, it will continue studies evaluating pelacarsen as a treatment for calcific aortic valve stenosis.

Ionis' stock (IONS) plunged 28.1% on Monday morning in response to the data and its third-quarter results, which included lowering sales guidance for Tryngolza, another heart drug.

Swiss-listed shares of Novartis (CH:NOVN) were up 0.3%.

Pelacarsen is an antisense oligonucleotide, which blocks production of certain proteins that can damage the heart. In the "Horizon" trial, the drug reduced lipoprotein(a), which is similar to "bad" cholesterol - except it's inherited. Changing your diet or taking a statin doesn't lower Lp(a). Scientists believed that reducing Lp(a) would lead to a reduction in serious heart events. In 2025, one doctor even described targeting Lp(a) as "the next frontier in cardiovascular disease."

But now that the study's results are out, pelacarsen's failure raises questions about similar LP(a)-lowering therapies being developed by other drugmakers. That includes Eli Lilly's (LLY) lepodisiran and Amgen's (AMGN) olpasiran, both of which are in Phase 3 studies. Analysts have said they expect olpasiran to 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 trading at its lowest price this year. Its closing price was $38.80 on Thursday, down from its year-to-date high of $86.50 on Feb. 6.

-Jaimy Lee

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11-09-26 1016ET