Tozorakimab Phase III Data Establish IL-33 Pathway in COPD

On March 27, 2026, AstraZeneca reported positive phase 3 results (OBERON and TITANIA trials) for tozorakimab, an investigational monoclonal antibody (mAb), which successfully demonstrated that an interleukin-33 (IL-33)–targeting biologic can reduce exacerbations in chronic obstructive pulmonary disease (COPD). According to the company, the findings represent a milestone that could expand biologic treatment beyond eosinophil-driven subtypes.¹

High-level data from the replicate OBERON and TITANIA trials, both part of the company’s phase 3 LUNA program, showed “statistically significant” and “clinically meaningful” reductions in the annualized rate of moderate-to-severe exacerbations versus placebo, which the company said positions the mAb as a potential first-in-class option in a broad COPD population.¹

“These trial results suggest that targeting the IL-33 pathway with tozorakimab delivers meaningful clinical benefit in a trial representing a broad COPD population, independent of smoking status and eosinophilic levels,” said Frank Sciurba, MD, professor of Pulmonary and Critical Care Medicine at the University of Pittsburgh and chief investigator of the LUNA program, in a company press release.¹ “COPD has long been a difficult-to-treat disease with inherent heterogeneity and significant unmet need … underscoring the importance of these results for advancing COPD science.”

What exactly did the trials show and why are these results significant?

The trials evaluated tozorakimab 300 mg administered every four weeks on top of standard inhaled therapy in adults with symptomatic COPD who continued to experience exacerbations. Across both studies, efficacy was observed in the primary population of former smokers and in the overall population, which included both current and former smokers, spanning all eosinophil levels and lung function severities. The therapy was generally well tolerated, with a safety profile consistent with prior studies.^2,3

COPD affects nearly 400 million people globally and remains the third leading cause of death worldwide. Despite maintenance inhaled therapies, more than half of patients experience exacerbations, which accelerate disease progression and increase the risk of hospitalization and mortality. Existing biologics have shown benefit primarily in eosinophilic subpopulations, limiting their broader applicability.⁴

Tozorakimab targets IL-33, an upstream cytokine implicated in inflammation and tissue damage. Unlike other approaches, the mAb inhibits both reduced and oxidized forms of IL-33, aiming to suppress inflammatory signaling while disrupting mucus dysfunction, which are two key drivers of disease worsening. This dual mechanism may enable efficacy across a more heterogeneous patient population.⁵

“Today’s tozorakimab results deliver the first two confirmatory [phase 3] trials for an IL-33 biologic, which is a major scientific advancement in COPD,” said Sharon Barr, PhD, executive vice president, BioPharmaceuticals R&D, AstraZeneca, in the release.¹ “Tozorakimab works in a fundamentally different way … to both decrease inflammation and disrupt the cycle of mucus dysfunction that are key disease drivers in COPD.”

What is next in the mAb’s regulatory pathway?

The OBERON and TITANIA trials enrolled a combined 2306 patients and were designed as double-blind, placebo-controlled studies. The primary endpoint was the annualized rate of moderate-to-severe exacerbations in former smokers, with key secondary analyses assessing outcomes in the broader population. Patients received treatment for 52 weeks in addition to standard-of-care inhaled therapy.^2,3

Additional phase 3 trials under the LUNA program are ongoing. The PROSPERO extension study is evaluating long-term outcomes over 104 weeks, with results expected in the first half of 2026. The MIRANDA trial is assessing an alternative dosing regimen, with data also anticipated in 2026. Beyond COPD, tozorakimab is being studied in severe viral lower respiratory tract disease and asthma, reflecting broader potential across respiratory indications.

Full data from OBERON and TITANIA are expected to be presented at an upcoming medical meeting.¹ If confirmed, these findings could redefine the biologic treatment landscape in COPD by introducing a mechanism capable of addressing multiple disease drivers across diverse patient populations, potentially shifting clinical practice toward earlier and more inclusive use of targeted therapies.

References

1. AstraZeneca. Tozorakimab met primary endpoint in both OBERON and TITANIA Phase III trials in patients with COPD. Published March 27, 2026. Accessed March 27, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/tozorakimab-met-primary-endpoint-in-oberon-titania-phase-iii-trials-in-patients-with-copd.html
2. Efficacy and safety of tozorakimab in symptomatic chronic obstructive pulmonary disease with a history of exacerbations (OBERON). ClinicalTrials.gov; NCT05166889. Updated Jan. 16, 2026. Accessed March 27, 2026. https://clinicaltrials.gov/study/NCT05166889
3. Efficacy and safety of tozorakimab in symptomatic chronic obstructive pulmonary disease with a history of exacerbations. (TITANIA). ClinicalTrials.gov; NCT05158387. Updated Jan. 16, 2026. Accessed March 27, 2026. https://clinicaltrials.gov/study/NCT05158387
4. de Oca MM, Perez-Padilla R, Celli B, et al. The global burden of COPD: epidemiology and effect of prevention strategies. Lancet Respir. Med. 2025;13(8):709-724. doi: 10.1016/S2213-2600(24)00339-4
5. England E, Rees DG, Scott IC, et al. Tozorakimab (MEDI3506): an anti-IL-33 antibody that inhibits IL-33 signalling via ST2 and RAGE/EGFR to reduce inflammation and epithelial dysfunction. Sci Rep. 202;13(1):9825. doi: 10.1038/s41598-023-36642-y