NEW YORK — Amgen built the case for olpasiran, its experimental cholesterol drug, on a premise that seemed scientifically sound: lower Lp(a) levels in the blood, lower cardiovascular risk. On September 8, a Novartis trial failure made that premise a question.
Amgen shares closed at $397.77, down $39.34, or 9.0%, as investors repriced the entire Lp(a) drug class following Novartis’ Phase 3 trial defeat, compounded by a morning analyst downgrade. The session erased roughly one month of gains and ranked as one of the stock’s worst single-day declines in recent years.
The Novartis data landed four days earlier. According to BioPharma Dive’s reporting on the Lp(a)HORIZON trial, pelacarsen enrolled 8,323 patients with elevated Lp(a) and established cardiovascular disease. The drug succeeded at the biomarker level, reducing Lp(a) concentrations meaningfully, yet failed to translate that biological effect into fewer cardiovascular deaths, heart attacks, or strokes compared with placebo. Markets absorbed the first shock on September 4 and 5. September 8 brought the secondary wave as institutional investors recalibrated the pipeline’s worth.
Amgen’s olpasiran targets the same biological pathway through a different mechanism: a small interfering RNA therapy designed to silence the gene responsible for Lp(a) production. An earlier Phase 2 study showed that olpasiran reduced Lp(a) levels by more than 90%, a result that fueled substantial investor optimism around Amgen’s cardiovascular drug pipeline. Novartis’ pelacarsen Phase 3 failure now raises an unavoidable question for Amgen stock investors: if lowering Lp(a) concentrations does not reduce cardiovascular events, what does a 90% biomarker reduction in Phase 2 actually predict for an eventual Phase 3 trial outcome?
Drug development has navigated similar paradoxes before. Statins reduce LDL cholesterol and conclusively lower cardiovascular risk. CETP inhibitors, developed over decades, also reduced LDL in trials but repeatedly failed to show cardiovascular benefit despite the biomarker effect, costing billions in abandoned programs. If Lp(a) follows the CETP pattern rather than the statin pattern, olpasiran’s Phase 3 program, for which Amgen has not yet disclosed a readout timeline, faces a fundamental rethink.
BMO Capital Markets analyst Evan Seigerman amplified the pressure with a downgrade to Market Perform from Outperform, maintaining a $450 price target but citing more balanced risk-reward following Amgen’s 34% year-to-date advance heading into Monday’s session. The stock reached a 52-week high of $447.03 just weeks before September 8. At $397.77, shares have now retreated nearly 11% from that peak.
Amgen’s financial position heading into September was a point of strength before the session. Per the Q2 2026 earnings release filed with the Securities and Exchange Commission, revenue rose 10% year over year to more than $10 billion, with 22 products posting double-digit sales growth. Management raised full-year revenue guidance to $38.8 billion at the midpoint and increased non-GAAP EPS guidance to $22.90. Thomas Dittrich returned to the company as chief financial officer, effective September 1.
The broader market provided no shelter. The Dow Jones Industrial Average fell 628 points on September 8, driven by Brent crude surging toward $99 a barrel following Houthi drone strikes on Saudi Aramco’s Jizan refinery complex and Canada’s retaliatory tariffs taking effect. American Express fell 1.11% in that selloff, with financials bearing the brunt of rate-path uncertainty. Amazon outperformed sharply, slipping just 0.66% after a Qualcomm AI chip deal provided company-specific counterweight. Amgen’s decline was of a different character: a science question whose answer will not come until olpasiran’s Phase 3 data arrives.
Eli Lilly, which is also developing an Lp(a)-targeting therapy, saw shares fall in sympathy. The class-wide move reflects how capital repositions when a shared biological thesis is challenged. The question before investors is not limited to pelacarsen or to Novartis, but to whether lowering Lp(a) levels translates into the same cardiovascular protection that LDL reduction has delivered for decades.
Amgen Inc. trades on the Nasdaq exchange under the ticker AMGN. The stock closed Monday at $397.77, down $39.34 from its Friday close of $437.11.
