Amgen Shares Fall About 10% After Novartis Says Pelacarsen Missed Its Main Goal in a Phase III Heart Trial

A Failed Trial Called Itself "Important New Evidence"

Novartis put out the news itself on September 4: its cholesterol-lowering drug pelacarsen had missed the main goal of its biggest trial^[1]. The drug did what it was designed to do — it lowered levels of a blood particle called lipoprotein(a), or Lp(a), in patients who had it^[1]. But lowering that number didn't translate into fewer heart attacks, strokes, cardiovascular deaths, or urgent artery procedures, the four things the trial was actually built to prevent^[1].

That's the tension sitting at the center of this story. A drug can move the marker doctors watch and still fail the test that matters to patients. Novartis's own headline on the release didn't use the word "fail" at all. It called the result "important new evidence on the relationship between Lp(a) lowering and cardiovascular outcomes^[1]."

The trial, called Lp(a)HORIZON, enrolled 8,323 people who already had heart disease and high Lp(a)^[1][18]. Every one of them was already on standard treatment — statins and blood-pressure drugs^[1]. Novartis says it will present the full data at a medical conference rather than just in a press release^[1].

What Lp(a) Actually Is, and Why Nobody Can Treat It Yet

Lp(a) is a cholesterol-carrying particle. Unlike regular cholesterol, which diet and exercise and statins can budge, Lp(a) is set almost entirely by a person's genes^[1]. You can do everything right and still carry the risk.

Roughly one in five people worldwide have elevated Lp(a), according to Novartis, and there is no approved drug that targets it specifically^[1]. Scientists have long known that people who are born with naturally low Lp(a) tend to have less heart disease. That genetic pattern is what convinced drugmakers that lowering Lp(a) with a medicine, later in life, should help too.

Pelacarsen was built to test that idea directly. It's what's called an antisense oligonucleotide — a lab-made strand that binds to the body's own instructions for building the Lp(a) protein and blocks them, so less of it gets made. Amgen's competing drug, olpasiran, and Eli Lilly's, lepodisiran, work on the same instructions but through a different chemical route, called siRNA, dosed on a different schedule.

That distinction is the crux of the argument now playing out among drugmakers and analysts: is this one drug's failure, or a strike against the whole strategy of lowering Lp(a) to prevent heart attacks?

The Selloff Didn't Match the News, Because Not All the Stocks Are the Same Stock

Money moved before that question got answered, and it moved differently depending on where you looked. Novartis's Zurich-listed shares — the deep, primary market for the company — fell about 1.9% on Monday, September 7, wiping out roughly 4.9 billion Swiss francs of value^[7]. For a company Novartis's size, that's a bad day, not a crisis.

Ionis Pharmaceuticals, the smaller biotech that discovered pelacarsen and shares in its economics, took a much harder hit: down about 12% in after-hours trading the night of the announcement, and about 9.8% pre-market the following Tuesday^[3][8]. Pelacarsen is a much bigger piece of what Ionis is worth than it is of Novartis, so the same news landed harder there.

Amgen, which has no financial stake in pelacarsen at all, still fell about 9.8% on Tuesday, September 8, closing at $394.56 — its worst single day since October 2000^[12]. That morning, BMO Capital Markets downgraded Amgen from Outperform to Market Perform, while keeping its price target at $450^[11]. BMO's note didn't blame pelacarsen alone; it also pointed to Amgen's own obesity drug, MariTide, and to the fact Amgen shares had already climbed about 34% for the year, well ahead of the S&P 500 and the rest of the drug sector^[11].

Some retail-investor outlets ran a much bigger number for Novartis itself — one headline paired "Amgen Falls 10%" with "NVS Stock Drops 14%^[9]." That 14% figure appears to trace to a thin, pre-market quote on Novartis's much smaller U.S.-listed shares, not the Zurich exchange where the stock actually trades^[7][8][9]. Reuters, sourcing the deeper market, put the real move at 1.9%^[7].

Why a Company With No Skin in This Trial Lost the Most Value

Amgen's drop is what traders call a "read-through" — investors betting that if Novartis's approach to lowering Lp(a) failed, Amgen's own effort probably will too, even though the two drugs aren't identical. Amgen's olpasiran is still in its own Phase III trial, called OCEAN(a), with results expected around 2027 or 2028^[6][11]. Lilly's lepodisiran won't report until 2029^[6][14]. Until either of those trials reads out, there's no new data — just inference from Novartis's result.

That's why Amgen and Lilly's defenders argue the market moved too fast. An analyst note covering the sector said the bet on olpasiran "shifts to a higher-risk/higher-reward rather than becoming outright impaired," pointing to real differences in chemistry and dosing between the drugs^[9]. JPMorgan, more cautiously, said the pelacarsen result lowers expectations for olpasiran ahead of its own readout^[11]. Citi's Geoff Meacham said the field needs the full pelacarsen data to know whether the miss reflects the drug itself, an insufficient drop in Lp(a), the trial's design, or a real problem with the underlying idea — and warned that "the first dedicated outcomes failure lowers confidence across the class and places greater pressure on later studies^[3]."

Underneath the market moves sits a structural fact that applies to every drugmaker in this race: large companies need their next big product lined up before older ones lose patent protection, so a late-stage failure gets punished harder in expectations than it costs in actual cash today^[5][6][11]. None of these companies has pulled a product already on the market, and none has cut its financial guidance over this^[1][18].

The Argument Nobody Can Settle Until 2028

For Novartis and Ionis, the case is that a negative trial is still real science, not wasted money. Every patient in the study was already on modern standard care, which leaves less room for any add-on drug to show extra benefit^[1]. They argue the answer may be hiding in how deep the Lp(a) drop went, in which patients, and over what timeframe — details that will come with the full dataset^[1].

Ionis has more riding on the outcome per dollar of its own value. In 2023, it sold Royalty Pharma a stake in royalty streams tied to two of its drugs, Spinraza and pelacarsen, for up to $1.125 billion, a deal built mainly around Spinraza but with pelacarsen as an added upside^[8]. Novartis needs pipeline wins to replace revenue from older drugs losing patent protection^[5][6].

For cardiologists and patients with elevated Lp(a), the stock swings are beside the point. The real question is whether a drug given for a few years, late in someone's disease, can reproduce the protective effect seen in people born with naturally low Lp(a) over a lifetime. That question stays open until Amgen's and Lilly's trials report, in 2028 and 2029^[6][14].

Coverage of all this split along familiar lines. Company statements framed the miss as a contribution to science, without disclosing the actual numbers behind it^[1]. Science-focused outlets like STAT led with what the result means for the biology, keeping stock prices low on the page^[4]. Retail-investor sites reached for the largest percentage available, even when it came from a thin pre-market quote that didn't match where the stock actually closed^[7][8][9]. Swiss coverage, by contrast, sized the loss in francs and treated it as a setback for one company's pipeline, not a verdict on the whole drug class^[7][13].