Novo Nordisk ends two more phase 3 trials

Novo Nordisk has scrapped two more phase 3 trials for its drug candidate ziltivekimab. The Danish drugmaker confirmed the termination of the Hermes and Athena studies to Fierce Biotech after a data monitoring committee assessed the totality of the data.

The decision follows the failure of a related phase 3 trial called Zeus in July. That study, which targeted atherosclerotic cardiovascular disease, chronic kidney disease, and inflammation, missed its primary endpoint. The committee concluded the new heart failure trials had a low likelihood of a different outcome from the Zeus results.

Trial details and patient enrollment

The halted trials were investigating ziltivekimab, an IL-6 ligand, in patients with specific types of heart failure. The larger Hermes trial had enrolled 4,900 participants, while the Athena trial had enrolled 673 patients. Both studies focused on heart failure with mildly reduced or preserved ejection fraction.

The primary goal for both trials was to see if the drug could delay death or hospitalization from heart failure. According to the federal trials database, the Hermes trial was originally scheduled to read out results in the first half of 2027. Novo Nordisk notified investigators of the early termination on Friday.

Impact on blockbuster potential

Analysts had once seen significant commercial potential in ziltivekimab. Before the Zeus trial failed, BMO analysts described it as an important opportunity for Novo to expand its cardiovascular presence beyond obesity and diabetes. They suggested the drug could achieve peak sales of around $3 billion.

The consecutive trial failures cast doubt on the scientific approach. Jefferies analysts previously noted that the Zeus failure "calls into question whether IL-6/hsCRP reduction is a viable target in ASCVD." They added it was a blow to the NLRP3 thesis, which sits upstream of IL-6. With the end of Athena and Hermes, that underlying scientific thesis faces further scrutiny.

Remaining study and future prospects

Novo Nordisk's hopes for ziltivekimab now rest entirely on a single ongoing phase 3 trial named Artemis. This study is testing the drug in patients following an acute heart attack. The company told Fierce Biotech that Artemis will "continue as planned." A readout is scheduled for the first half of next year.

The future of the entire program hinges on the Artemis results. If that trial also fails, it would end development for ziltivekimab. Such an outcome would eliminate one of Novo Nordisk's key pipeline projects aimed at expanding beyond its core, though highly profitable, focus on obesity and diabetes treatments. The company had previously warned that the Zeus trial was always a long shot.