Key takeaways
- Novo Nordisk’s U.S.-listed shares closed 8.8 per cent lower after ziltivekimab failed a pivotal cardiovascular trial.
- The drug produced the expected biological response but did not reduce cardiovascular deaths, non-fatal heart attacks or non-fatal strokes.
- The ZEUS trial’s hazard ratio of 0.99 indicated virtually no difference between ziltivekimab and placebo.
- Novo will record a non-cash impairment charge but has maintained its 2026 adjusted operating-profit outlook.
- Two additional ziltivekimab trials will continue, although analysts have become increasingly sceptical about their prospects.
Novo Nordisk A/S (NYSE:NVO) shares tumbled Friday after the Danish pharmaceutical company’s experimental cardiovascular drug failed to reduce major adverse cardiovascular events in a Phase 3 trial.
The stock closed 8.8 per cent lower at US$47.08 after falling as low as US$45.45 during the session. Shares traded in Copenhagen ended approximately 7.7 per cent lower at 306.50 Danish kroner.
The result removes one of Novo Nordisk’s most closely watched opportunities to expand beyond the obesity and diabetes medicines that generated more than 90 per cent of its sales last year.
Ziltivekimab produces no cardiovascular benefit
The ZEUS trial enrolled more than 6,300 people with atherosclerotic cardiovascular disease, chronic kidney disease and elevated inflammation.
Participants received either a 15-milligram injection of ziltivekimab once monthly or a placebo alongside standard care. The primary endpoint measured the time until cardiovascular death, a non-fatal heart attack or a non-fatal stroke.
Ziltivekimab successfully inhibited the IL-6 inflammatory pathway and reduced levels of free IL-6 and high-sensitivity C-reactive protein. However, those biological effects did not translate into fewer cardiovascular events.
The trial produced a hazard ratio of 0.99, with a 95 per cent confidence interval of 0.88 to 1.11. A hazard ratio of 1 would indicate identical event rates, meaning the result showed virtually no difference between the treatment and placebo groups.
“Although ziltivekimab produced the expected biological effect, this did not result in MACE benefits in this population,” Chief Scientific Officer Martin Holst Lange said in Novo Nordisk’s announcement.
Analysts had generally considered a relative risk reduction of at least 15 per cent necessary to support the drug’s regulatory and commercial prospects.
Serious infections occur more frequently
Overall adverse-event and serious adverse-event rates were similar between the two trial groups. However, serious infections occurred more frequently among patients receiving ziltivekimab, consistent with the known risks of inhibiting IL-6.
Novo Nordisk reported no difference in deaths from all causes.
The safety finding added to concerns surrounding anti-inflammatory cardiovascular treatments. Novartis previously failed to secure U.S. approval for canakinumab after the drug reduced cardiovascular events but increased the risk of fatal infections.
The ZEUS result also raises wider questions about whether reducing inflammatory biomarkers such as high-sensitivity C-reactive protein will reliably prevent cardiovascular events.
Failure weakens diversification strategy
Novo Nordisk acquired ziltivekimab through its 2020 purchase of Corvidia Therapeutics. The company paid US$725 million upfront, with the transaction potentially worth as much as US$2.1 billion through milestone payments.
Consensus estimates had placed potential peak annual sales at approximately US$3 billion. UBS had assigned a 60 per cent probability to that forecast and estimated that the program represented 1.7 per cent of Novo Nordisk’s net present value.
The financial impact therefore represents only part of investors’ concern. The trial failure compounds pressure on Novo’s research pipeline as the company seeks growth beyond Wegovy and Ozempic while competing with Eli Lilly and Company (NYSE:LLY) in the obesity market.
TD Cowen described ZEUS as a missed opportunity to broaden Novo Nordisk’s investment case. BMO Capital Markets said a major acquisition in cardiovascular, metabolic or rare diseases could help restore investor interest.
Novo said the result would not change its previously issued 2026 adjusted operating-profit outlook. It will nevertheless record a non-cash impairment charge during the third quarter, with the amount yet to be disclosed.
Two additional trials will continue
Novo Nordisk plans to continue two other Phase 3 cardiovascular-outcomes trials involving ziltivekimab.
HERMES is testing the drug in people with heart failure, while ARTEMIS is studying patients following an acute heart attack. Both trials are expected to report results during the first half of 2027.
BMO analysts said positive results from either study now appear “highly unlikely,” although the different patient populations mean ZEUS does not determine their outcomes.
The failure also has no direct bearing on the effectiveness of Wegovy, Ozempic or Novo Nordisk’s other GLP-1 medicines, which use a different mechanism. However, it leaves the company more dependent on its existing obesity and diabetes portfolio while investors await evidence of a successful new growth driver.