Tozorakimab Cuts COPD Exacerbations Up to 34% in Phase 3 Trials

Tozorakimab, an investigational monoclonal antibody targeting interleukin-33 (IL-33), significantly reduced the rate of moderate and severe chronic obstructive pulmonary disease (COPD) exacerbations compared with placebo in 2 replicate phase 3 trials, with the benefit holding regardless of patients’ smoking status or blood eosinophil count, according to results published in the New England Journal of Medicine and presented at the European Respiratory Society (ERS) Congress 2026 in Barcelona, Spain.^1,2

The findings from the OBERON and TITANIA trials position tozorakimab as a potential add-on option for a wider swath of patients with COPD than the biologics currently on the market, most of which are restricted to patients with elevated blood eosinophil counts.^2,3

“We all know COPD exacerbations are important events in the lives of our patients,” Frank Sciurba, MD, professor of pulmonary and critical care medicine at the University of Pittsburgh and chief investigator of the trial program, said during a presentation of the late-breaking data at ERS. “They result in downstream effects on quality of life, accelerated decline in lung function, and cost effects on hospitalization as well as death. Despite this, most of our patients continue to exacerbate, despite guideline-based therapy.”

How Did Tozorakimab Perform in OBERON and TITANIA?

OBERON and TITANIA were identically designed, double-blind, placebo-controlled trials that enrolled a combined 2306 adults with symptomatic COPD who continued to have exacerbations despite stable inhaled maintenance therapy, most often triple therapy.^2,3 Patients received subcutaneous tozorakimab, 300 mg every 4 weeks or placebo for 52 weeks on top of their existing regimen.

The primary end point, the annualized rate of moderate or severe exacerbations among former smokers, dropped 29% with tozorakimab in OBERON and 34% in TITANIA compared with placebo. In the overall population of current and former smokers, a key secondary end point, exacerbation rates fell 30% in OBERON and 29% in TITANIA. Both trials capped enrollment of current smokers at 25% and included patients across the full severity spectrum, down to Global Initiative for Chronic Obstructive Lung Disease grade 4 (very severe) airflow obstruction.^1,3

Sciurba called the results “statistically and clinically” significant, and “all subpopulations showed a nearly consistent effect with tozorakimab.”¹ The drug was effective independent of severity and independent of eosinophil level.

“Tozorakimab, a first-in-class biologic, demonstrates a valuable potential therapeutic agent for our patients with COPD who continue to exacerbate despite guideline-based therapy,” Sciurba said.

Why Does Efficacy Across Eosinophil Levels Matter for Access?

A prespecified pooled subgroup analysis of the 2 trials found that treatment effects were consistent across current and former smokers, disease severity, and blood eosinophil thresholds.^2,3 Patients with eosinophil levels less than 150 cells/µL, an area of unmet need, had a 23% reduction in exacerbation rate. Patients at or above 150 cells/µL had a 34% reduction, and patients with at or above 300 cells/µL had a 43% reduction in exacerbation, Sciurba said before being interrupted by a spontaneous applause from the audience.¹

The 2 biologics currently approved for COPD, dupilumab (Dupixent; Sanofi and Regeneron) and mepolizumab (Nucala; GSK), are indicated only for patients with elevated eosinophil counts, leaving a substantial share of exacerbation-prone patients without an add-on biologic option.² Because tozorakimab inhibits both the reduced and oxidized forms of IL-33, which act on inflammatory and epithelial repair pathways beyond classic type 2, eosinophil-driven pathways, it benefits patients independent of eosinophil status, according to the new phase 3 data.

What Do the Safety Data for Tozorakimab Show?

Adverse events were generally balanced between tozorakimab and placebo groups in both trials, with rates of 70.4% versus 77.2% in OBERON and 80.1% versus 79.8% in TITANIA.² Serious adverse events were similarly comparable, occurring in 23.3% versus 27.0% of patients in OBERON and 31.1% versus 32.4% in TITANIA. The most consistent difference was injection site reactions, which were more common with tozorakimab, an effect investigators noted is typical of subcutaneously administered monoclonal antibodies.^2,3

Major adverse cardiovascular events (MACE) and deaths were rare but occurred somewhat more often with tozorakimab than placebo across the pooled trials.²

“There was very low MACE signal, although there was a slight imbalance, which we attribute to a remarkable absence of MACE events in the placebo group,” Sciurba said during his presentation. “But overall, I think this would be judged as safe.”

What's Next for Tozorakimab's Regulatory Path?

AstraZeneca's biologics license application for tozorakimab, 300 mg every 4 weeks, has been accepted for priority review by the FDA as an add-on maintenance treatment for adults with COPD, with a Prescription Drug User Fee Act decision anticipated in the first quarter of 2027.³

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 6571. Presented at: European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.
2. Sciurba FC, Watz H, Bourdin A, et al. Tozorakimab to prevent COPD exacerbations. N Engl J Med. Published online September 8, 2026. doi:10.1056/NEJMoa2606998
3. Tozorakimab demonstrated statistically significant and highly clinically meaningful reduction in COPD exacerbations in OBERON and TITANIA Phase III trials. News release. AstraZeneca. September 8, 2026. Accessed September 8, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/tozorakimab-demonstrated-statistically-significant-highly-clinically-meaningful-reduction-copd-exacerbations-oberon-titania-phase-iii-trials.html