Novo’s blockbuster hopes for CKD program dwindle after more phase 3 trials scrapped

Novo Nordisk has given up on two more phase 3 trials of ziltivekimab, further eroding the prospects for a molecule that analysts had once tipped as a potential blockbuster. The Danish drugmaker had been evaluating the IL‑6 ligand in the late-stage Hermes and Athena trials, which enrolled 4,900 and 673 patients, respectively, with heart failure with mildly reduced or preserved ejection fraction. Success in both trials was to be judged by ziltivekimab’s ability to delay death or hospitalization from heart failure. The original plan, according to the federal trials database, had been to read out Hermes in the first half of 2027. But Novo notified investigators on Friday that it was winding up both of the studies early. The pharma made the decision after the trials’ data monitoring committee had assessed “the totality of the data,” Novo confirmed to Fierce. Specifically, the committee had assessed the “low likelihood of a different outcome from Zeus”—a reference to a phase 3 trial in atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease and inflammation which missed its primary endpoint in July. Before Zeus crashed down to earth, analysts at BMO had described ziltivekimab as “an important opportunity for Novo to extend its cardiovascular presence beyond obesity/diabetes,” while suggesting peak sales of around $3 billion. Despite Novo execs having warned that the Zeus trial was always going to be a long shot, that study’s failure still caused some consternation, with Jefferies analysts reflecting at the time that the fail “calls into question whether IL-6/hsCRP reduction is a viable target in ASCVD, and by extension is a blow to the NLRP3 thesis, which sits upstream of IL-6.” With Athena and Hermes also confirmed as duds, that thesis looks even further in doubt. Novo’s hopes for ziltivekimab now rest with Artemis, a phase 3 study in patients following an acute heart attack. Novo told Fierce that Artemis will “continue as planned,” with a readout penciled in for the first half of next year. If Artemis also falls short, bringing to an end any hopes for ziltivekimab, it will wipe out one of Novo’s best shots at expanding beyond its narrow, if lucrative, comfort zone of obesity and diabetes.