AstraZeneca Tozorakimab BLA Accepted for FDA Priority Review in COPD

AstraZeneca (AZN ) said on 8 September 2026 that the US Food and Drug Administration has accepted for Priority Review its Biologics License Application for tozorakimab 300mg, administered once every four weeks, as an add-on maintenance treatment for adults with chronic obstructive pulmonary disease. The application is supported by full results from the Phase III OBERON and TITANIA trials, in which the company said tozorakimab became the first biologic to show statistically significant and highly clinically meaningful reductions in moderate and severe COPD exacerbations across a broad patient population. AstraZeneca said the Prescription Drug User Fee Act date is anticipated during the first quarter of 2027, following use of a Priority Review voucher.

According to the company’s announcement, tozorakimab reduced the annualised rate of moderate and severe exacerbations in the primary population of former smokers by 29% in OBERON and 34% in TITANIA compared with placebo while patients remained on inhaled standard of care. In the overall population of current and former smokers, the reductions were 30% in OBERON and 29% in TITANIA. The trials enrolled patients across all blood eosinophil counts and all stages of lung function severity.

In a pooled analysis of the two trials, AstraZeneca reported clinically meaningful reductions in moderate and severe exacerbations across all prespecified patient subgroups, including subgroups defined by blood eosinophil count. Patients with a baseline blood eosinophil count below 150 achieved a 23% reduction, patients at or above 150 achieved a 34% reduction, and patients at or above 300 achieved a 43% reduction.

The full results were presented as a late-breaker oral presentation in the ALERT-2 plenary session at the European Respiratory Society Congress 2026 in Barcelona and were simultaneously published in the New England Journal of Medicine. In a separate poster presentation at the congress, AstraZeneca presented an integrated analysis of OBERON and TITANIA that it said demonstrated a reduction in patients’ mucus plug score, which it described as an emerging outcome measure associated with worse outcomes in COPD.

Tozorakimab was generally well tolerated with a favourable safety profile, the company said, with injection-site reaction the only adverse drug reaction identified.

Trial Design and Patient Population

OBERON and TITANIA were replicate Phase III double-blind, placebo-controlled trials in adults with symptomatic COPD who had a history of at least two moderate or at least one severe exacerbation in the 12 months before enrolment. A total of 2,306 patients were randomised across the two trials, including former and current smokers, patients across all blood eosinophil counts, and patients at all stages of lung function severity.

Patients received tozorakimab 300mg once every four weeks, or placebo, over 52 weeks on top of inhaled therapy. Before enrolment, patients had received standard-of-care inhaled maintenance therapy for at least three months. The primary endpoint was the annualised rate of moderate-to-severe COPD exacerbations in former smokers, and a key secondary endpoint measured the same rate in the overall population of former and current smokers.

Mechanism and Regulatory Position

Tozorakimab is a potential first-in-class monoclonal antibody targeting interleukin-33. According to AstraZeneca, it uniquely inhibits the signalling of both the reduced and oxidised forms of IL-33, offering the potential to reduce inflammation and disrupt the cycle of mucus dysfunction that contributes to COPD worsening.

Beyond the US filing, tozorakimab is under regulatory review for COPD in other major markets, including the European Union and China. The drug is also being studied in a Phase II trial in severe asthma and a Phase III trial in severe viral lower respiratory tract disease. The FDA granted Fast Track Designation to tozorakimab for severe viral lower respiratory tract disease in November 2023 and for COPD in December 2024.

“AstraZeneca has clinically validated the novel approach of targeting the signalling of the two forms of IL-33 to both decrease inflammation and disrupt the cycle of mucus dysfunction,” Sharon Barr, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, said in the announcement. “With our FDA Priority Review, we look forward to bringing this treatment to patients as quickly as possible.”

Frank Sciurba, Professor of Pulmonary and Critical Care Medicine at the University of Pittsburgh and Chief Investigator of the LUNA programme, said the trials marked the first time a biologic in COPD achieved efficacy across blood eosinophil thresholds, including in patients with baseline eosinophils below 150, and irrespective of smoking status.

Programme Background

AstraZeneca announced positive high-level results from OBERON and TITANIA on 27 March 2026, reporting at that time that tozorakimab met its primary endpoint in both trials. The tozorakimab Phase III COPD development programme, known as LUNA, includes four clinical trials: OBERON, TITANIA, PROSPERO, and MIRANDA. PROSPERO is a long-term extension trial that enrolled 1,713 patients who completed OBERON or TITANIA, with a primary endpoint of the annualised rate of severe exacerbations in former smokers over 104 weeks. MIRANDA randomised 1,454 patients to tozorakimab 300mg once every two weeks or placebo over 52 weeks.

COPD is the third leading cause of death worldwide excluding COVID-19, and nearly 400 million people are diagnosed with the disease. In the United States, exacerbations cause more than 2,500 emergency department visits per day, and only 50% of COPD patients live more than 3.5 years after their first severe exacerbation.