Amgen (AMGN) Fell 5% on a Drug That Isn’t Even Its Own. Here’s the Lp(a) Bet Now in Question.

Amgen Inc. (NASDAQ: AMGN ) shed roughly $12 billion in market value after hours on September 4, 2026. The stock declined by about 5% to $415. The reason, as strange as it sounds, is a drug it does not own. Novartis announced that pelacarsen, an Lp(a)-lowering therapy, missed its Phase 3 cardiovascular-outcomes trial, Lp(a)HORIZON. And since Amgen's late-stage asset olpasiran relies on the same biological premise, investors immediately marked down Amgen on the negative read-through.

The result strikes at a premise rather than at a product. Pelacarsenhad lowered Lp(a) by roughly 80% in earlier studies. In Lp(a)HORIZON, Novartis said pelacarsen substantially lowered Lp(a), but it still failed to reduce the composite of cardiovascular death, heart attack, stroke, and urgent revascularization. It still could not reduce the composite of cardiovascular death, heart attack, stroke, and urgent revascularization. And now the entire hypothesis that lowering Lp(a), a genetic cardiovascular risk factor, actually cuts events, is being directly challenged. Olpasiran is built on the same hypothesis, leading to the repricing of odds as soon as pelacarsen's data were out.

Amgen's olpasiran, an siRNA, lowered Lp(a) by more than 95% at certain doses in Phase 2, compared with reductions of roughly 80% for pelacarsen in earlier studies. The bull case is that this deeper reduction could help olpasiran deliver better cardiovascular outcomes.. The bull case is that this 15% will help Amgen to make a deeper cut and deliver results. While biologically possible, the Lp(a)HORIZON trial provided no evidence that a clinical threshold exists above an 80% reduction. The topline Phase 3 announcement did not establish that deeper Lp(a) lowering would have produced a cardiovascular benefit. It is therefore appropriate to say that the miss lowered olpasiran's probability of success rather than pretending it is irrelevant. Eli Lilly's lepodisiran is running the same deep-reduction experiment, so the hypothesis will be tested with or without Amgen.

Amgen is not an Lp(a) pure-play. MariTide in obesity, Repatha in cholesterol, and Tezspire in asthma drive more value for the company, and this diversification creates a cushion for the stock, although the selloff ultimately became much larger than the initial 5% after-hours reaction. Positioning has stayed calm since the beginning of 2026. Insider Monkey data shows 66 hedge funds held AMGN in the second quarter of 2026, up slightly from 65 in the first. Short interest, on the other hand, sits at just 2.4% of float, reflecting minimal bets against the stock in the market.