Ziltivekimab

iStock, Mohammed Haneefa Nizamudeen After the failure of Novo Nordisk’s IL-6 inhibitor ziltivekimab sent waves through the industry, the company has terminated two other studies of the asset, bringing the total number of high-pro flops to six over nine weeks. Novo Nordisk is ending two more late-stage studies for its investigational IL-6 inhibitor, citing expected futility and dimming prospects for the class as a whole in cardiovascular disease. The early discontinuations are for a pair of Phase 3 heart failure studies called HERMES and ATHENA , a spokesperson told BioSpace in a Tuesday email. The Danish pharma’s decision to shutter the studies early was “based on a recommendation from the Data Monitoring Committee on the totality of the data (including the low likelihood of a different outcome from ZEUS),” the spokesperson added. At the end of July, Novo’s IL-6 inhibitor ziltivekimab failed to reduce the risk of cardiovascular events in the late-stage ZEUS trial, dashing the pharma’s hopes for the heart inflammation program while also shaking other industry players working on the same pathway. “IL-6 now looks like an invalid target in chronic cardiovascular disease,” Oppenheimer analysts wrote on Tuesday. The industry had held out hope that the futility in ZEUS was potentially related to the trial’s population, which included patients with cardiovascular disease, chronic kidney disease and inflammation. Now, however, the futility terminations of both HERMES and ATHENA “remove the population-selection defense,” Oppenheimer said. HERMES enrolled nearly 5,000 patients with heart failure with mildly reduced ejection fraction and systemic inflammation, while ATHENA recruited 680 patients for the same type of heart failure. Immunology and inflammation Novo’s late-stage IL-6 stumble shakes inflammation space Novo Nordisk was banking on the inflammatory benefits of its investigational therapy ziltivekimab to improve cardiovascular outcomes. Last week’s Phase 3 failure dashed not just the Danish pharma’s hopes but that of other drugmakers working on the same pathway. August 3, 2026 · 2 min read · Tristan Manalac Read more With the addition of the two new trial fails, six total cardiovascular studies have flopped in just nine weeks, according to Oppenheimer. Beyond Novo’s three studies, AstraZeneca and Ionis Pharmaceuticals’ antisense oligonucleotide Wainua failed to significantly help patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), shaking the field’s confidence in the transthyretin silencer drug class. Most recently, Novartis’ antisense therapy pelacarsen showed no significant benefit on cardiovascular risk in a late-stage study. This outcome, analysts said, raises questions about a popular target for heart disease. When including Tenax Therapeutics’ late-stage flop for oral levosimendan in pulmonary hypertension due to heart failure with preserved ejection fraction, the findings have produced a narrative that cardiovascular outcome trials “are becoming unwinnable,” Oppenheimer said. But the analysts believe a deeper framing is needed, pointing to differences across the trials, such as attempts to treat different aspects of heart conditions and population variances. As for Novo, the obesity heavyweight is still waiting on results for another Phase 3 trial called ARTEMIS , which is testing ziltivekimab in the acute setting after heart attack. The study will continue as planned, with a readout slated for the first half of next year. “ARTEMIS remains active with lower expectations for success,” BMO analysts wrote Tuesday. The firm pointed to Novo’s Capital Markets Day, which will take place Sept. 21, as a near-term focus for investors. Novo’s stock has dipped 2% to $45.59 per share since market open on Tuesday. While Oppenheimer analysts were not entirely surprised about the new HERMES and ATHENA discontinuations, they did say they expect Novo shares “to be mildly pressured” by the announcement. Earnings Novo CEO sees innovation as a matter of survival amid pipeline setbacks Novo Nordisk CEO Maziar Mike Doustdar on a second quarter earnings call argued that failure is par for the course in the drug development business. The Danish pharma is focused on building out its pipeline to move past recent clinical roadblocks. August 5, 2026 · 3 min read · Tristan Manalac Read more

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.