Novo Nordisk’s IL-6 inhibitor ziltivekimab failed to reduce the risk of cardiovascular events in the late-stage trial, dashing hopes for an edge in the hyper-competitive cardiometabolic space.
Novo Nordisk’s gamble that reducing cardiovascular inflammation using an IL-6 inhibitor would result in fewer major adverse cardiovascular events appears to have fallen flat.
In a Phase 3 study of the IL-6 inhibitor ziltivekimab, the asset’s ability to reduce inflammation did not translate into risk reduction for cardiovascular events such as heart attack, stroke and death in patients with atherosclerotic cardiovascular disease, chronic kidney disease and inflammation, according to a Friday press release.
Novo was approaching the study, called ZEUS, as “high risk/high reward,” according to BMO Capital Markets, with the unfavorable result likely sending shares downward. Indeed, Novo’s stock price fell nearly 9% to $47.10 in Friday morning trading.
Novo’s high-profile rivalry with fellow industry behemoth Eli Lilly in the GLP-1 space has led the Danish company to seek differentiators that could give it an edge in the cardiometabolic area. As Lilly pulls away with sales of its GLP-1 drugs, Novo has scaffolded studies such as ZEUS to provide a pipeline that can stand out.
A previous mid-stage study of ziltivekimab demonstrated meaningful reduction in C-reactive protein, which measures inflammation, BMO analysts noted. But that biomarker study didn’t translate to the clinic.
ZEUS, the full results of which will be presented later this year, isn’t the end of the road for ziltivekimab. The IL-6 inhibitor is being examined in patients with heart failure through the HERMES study, as well as acute heart attack in the ARTEMIS study, both of which are expected to read out in the first half of next year. But the BMO analysts “view it as unlikely that either will read out positively” based on today’s findings.
“While ziltivekimab did not achieve the MACE benefit we had hoped for, this does not change our strategic commitment to cardiovascular disease,” Novo CSO Martin Holst Lange said in Friday’s release. “The study provides important scientific evidence that will inform our ongoing cardiovascular research and the development of treatments for patients who continue to face substantial unmet need.”
BMO analysts expect Novo to explore external business development following the high-profile failure, noting that the 2025 acquisition of Akero was “a good example of leaning into its strengths while still diversifying its potential revenue base.” Novo acquired ziltivekimab through the purchase of Corvidia Therapeutics for $725 million in 2020.
Novo will report second-quarter earnings next week, where analysts will look for updated details on the ongoing launch of oral Wegovy, as well as other pillars in the company’s obesity and metabolic portfolio. The weight loss pill has been a boon for Novo since its late-2025 approval, analysts have pointed out, but the company faces competition from Lilly’s Foundayo there, as well.
Meanwhile, Novo’s failure to prevent major cardiovascular events with the IL-6 inhibition approach rippled through the industry. Shares of BioAge, a smaller biotech with a Phase 1 NLRP3 inhibitor designed to address the same patient population and target effect, plummeted more than 50% Friday morning, which William Blair analysts in a Thursday note attributed to Novo’s news.
