Tozorakimab Cuts COPD Exacerbations Across Eosinophil Levels: Frank Sciurba, MD

Full phase 3 results from the replicate OBERON and TITANIA trials show tozorakimab, an anti-interleukin-33 (IL-33) monoclonal antibody, significantly reduced chronic obstructive pulmonary disease (COPD) exacerbations regardless of patients' blood eosinophil count (BEC) or smoking status, according to Frank C. Sciurba, MD, FCCP, professor of medicine at the University of Pittsburgh School of Medicine and chief investigator of the LUNA programme. Sciurba discussed the data, presented as a late-breaking oral presentation at the European Respiratory Society (ERS) Congress 2026 in Barcelona, Spain, held September 5 to 9, in an interview with HCPLive.

What benefits were seen with tozorakimab?

Tozorakimab 300 mg, dosed every 4 weeks, reduced moderate and severe exacerbations by 29% in OBERON and 34% in TITANIA in the primary population of former smokers, and by 30% and 29%, respectively, in the overall population of current and former smokers.1 In a pooled subgroup analysis, benefit scaled with eosinophil count but remained significant even at the low end: patients with a baseline BEC under 150 cells/µL had a 23% reduction in exacerbations, those at or above 150 cells/µL had a 34% reduction, and those at or above 300 cells/µL had a 43% reduction.1 Sciurba said that breadth matters clinically because most of the COPD biologics available before tozorakimab were effective mainly in the minority of patients with elevated eosinophils, leaving few options for the larger group with low or moderate counts.

“Our oath is to do no harm, and so once you get past that, then benefit is really clearly something that we embrace, and it does both, no harm and improvement,” he said of the safety profile.

On safety, Sciurba said there were no signals relative to placebo beyond the expected injection-site reactions, consistent with the study's characterization of injection-site reaction as the only identified adverse drug reaction.1 He noted a slight imbalance in major adverse cardiovascular events in one trial, but attributed it to an unusually low event rate in that trial's placebo arm given the comorbidity burden of the population, and said broader exposure data from the phase 2 and extension trials should clarify that this was an isolated finding rather than a true signal.

What effects did tozorakimab have on mucus plugging?

A separate poster from the same program showed tozorakimab reduced mucus plug burden on CT imaging, making it the first COPD biologic to demonstrate that effect in a broad population.2 Sciurba said this likely reflects the drug's unique mechanism, which blocks both the reduced and oxidized forms of IL-33, the latter of which acts on airway epithelial cells to drive mucus hyperplasia and airway remodeling independent of classic eosinophilic inflammation. He said mucus plugging is increasingly recognized as tied to higher mortality and symptom burden in COPD, and expects the field to learn more about how imaging-based mucus outcomes correlate with symptoms as more data emerge.

Next steps for tozorakimab?

Tozorakimab's Biologics License Application has been accepted for Priority Review by the FDA for COPD, with a Prescription Drug User Fee Act date anticipated in the first quarter of 2027. Sciurba said the drug will fill a real gap for patients who have exhausted other options.

“If you have frequent flare-ups and you're on guideline-based therapy, and you're still having a lot of bad days, I got a drug that can be beneficial and can offer hope,” he said.

Sciurba’s disclosures include AstraZeneca and others.

References

1. Sciurba FC, Watz H, Bourdin A, et al. Tozorakimab to prevent COPD exacerbations: results from the replicate OBERON and TITANIA phase 3 studies. Oral presentation at: European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.

2. Washko G, et al. Tozorakimab reduces the number of lung segments with mucus plugs in patients with COPD at high risk of exacerbations: integrated analysis of the replicate OBERON and TITANIA phase 3 studies. Poster presentation at: European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.