Danish pharmaceutical giant Novo Nordisk A/S (NVO.US) faced a significant research and development setback on Friday, announcing that its closely watched experimental heart drug, ziltivekimab, failed to meet its primary endpoint in a large-scale late-stage clinical trial, causing the company's stock to briefly plunge over 10% during trading.

The trial, named "Zeus," evaluated the monthly injectable IL-6 inhibitor ziltivekimab's ability to reduce the risk of major adverse cardiovascular events (MACE) compared to a placebo when added to standard therapy in a specific patient population. MACE was defined as cardiovascular death, non-fatal heart attack, or non-fatal stroke, with Jefferies estimating the market size at over $10 billion annually. The study enrolled more than 6,300 patients with atherosclerotic cardiovascular disease, chronic kidney disease, and elevated levels of inflammation.

Results showed that while the drug effectively reduced target proteins in the body, demonstrating biological activity, this effect did not translate into a statistically significant reduction in MACE risk. Regarding safety, overall adverse event rates were similar between the two groups, but the ziltivekimab group experienced a higher incidence of serious infections, while overall mortality rates showed no difference.

This outcome has deeply disappointed the market. Analysts had generally anticipated at least some degree of efficacy from the drug. Jefferies noted before the results were released that the study would need to show at least a 20% risk reduction to support widespread use, while BMO Capital Markets suggested that a 15% risk reduction combined with clean safety data could also be considered a positive signal. Goldman Sachs analysts stated prior to the results that a successful trial would have positioned ziltivekimab as a cornerstone for Novo Nordisk A/S to build a cardiovascular disease franchise, reducing the company's heavy reliance on Ozempic and Wegovy.

As a result of this setback, Novo Nordisk A/S's shares listed in Copenhagen tumbled as much as 10.5%, marking the biggest intraday drop since February, while its American Depositary Receipts (ADRs) also fell over 8% in pre-market trading. Despite retaining a 5% gain year-to-date as of Thursday's close, the company's shares in Denmark had already fallen 7% prior to this development.

Chief Scientific Officer Martin Holst Lange stated, "While ziltivekimab did not achieve the MACE benefit we hoped for, this does not change our strategic commitment to cardiovascular disease." The company confirmed it will continue advancing two other heart outcome trials for the drug, targeting patients with heart failure and those recovering from a recent acute heart attack, with results expected in the first half of next year. Competitors, including Novartis (NVS.US) and Eli Lilly (LLY.US), are also developing compounds targeting the same pathway. This failure to meet the primary endpoint is another blow for the Danish drugmaker, which is striving to restore investor confidence in its R&D pipeline and execution capabilities, particularly in the challenging U.S. market.