AZ’s COPD drug cuts flare-ups in two phase 3 trials

AstraZeneca’s experimental lung disease drug has significantly reduced COPD flare-ups in two late-stage trials, strengthening the case for a potential new biologic treatment for the condition.

Results from the phase 3 OBERON and TITANIA trials showed tozorakimab cut moderate-to-severe exacerbations significantly in former smokers, the trials’ primary population, compared with placebo.

Benefits across broad COPD population

COPD is a progressive lung disease that causes breathing difficulties, coughing and excess mucus production. Flare-ups can worsen the condition and increase the risk of hospitalisation and poorer long-term health outcomes.

More than 2,300 participants were randomised across the two trials. Eligible patients had symptomatic COPD and had experienced at least two moderate or one severe exacerbation in the previous 12 months despite receiving maintenance inhaled treatment.

Patients received either 300mg of tozorakimab or placebo every four weeks for 52 weeks alongside inhaled standard-of-care treatment.

AstraZeneca reports that the drug cut moderate-to-severe exacerbations in former smokers by 29% in OBERON and 34% in TITANIA, compared with placebo.

It also reduced exacerbations by 30% and 29%, respectively, in the overall trial populations, which included both current and former smokers.

Importantly, benefits were observed across blood eosinophil levels, including in patients with lower levels of the inflammatory cells. This could potentially broaden the population able to benefit from biologic treatment.

Tozorakimab, a monoclonal antibody, targets interleukin-33 (IL-33), a protein involved in inflammation and mucus dysfunction in the lungs.

Overall safety was generally similar between the tozorakimab and placebo groups, although injection-site reactions occurred more frequently with tozorakimab.

‘New standard’ for COPD treatment

The results represent the first time a biologic has demonstrated significant efficacy across such a broad COPD population in two replicate phase 3 trials, according to AstraZeneca.

The drugmaker’s application for tozorakimab is now under Priority Review by the FDA as an add-on maintenance treatment for adults with COPD, with a regulatory decision expected in the first quarter of 2027.

Study leader, Dr Frank Sciurba, University of Pittsburgh, said in a statement: “Reducing exacerbations is one of the most important goals in the treatment of COPD because flare-ups have a profound impact on patients’ health, quality of life and long-term outcomes. It is encouraging to have an additional, safe therapy for patients who often struggle to breathe.”

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Today’s groundbreaking tozorakimab results, from two replicate trials, set a new standard for COPD treatment outcomes in a broad population of patients.

“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. With our FDA Priority Review, we look forward to bringing this treatment to patients as quickly as possible.”

The results drew a positive response from some analysts, although AstraZeneca shares fell following the data release.

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