AstraZeneca is evaluating its oral IRAK4 inhibitor AZD6793 in a Phase 2b trial designed to test whether it can reduce COPD exacerbations.

Phase 2b trial tests AZD6793

The PRESTO trial is recruiting adults with moderate to very severe chronic obstructive pulmonary disease (COPD) who continue to experience exacerbations despite stable inhaled maintenance treatment.

AstraZeneca’s trial record describes PRESTO as a randomised, double-blind, placebo-controlled study comparing two doses of AZD6793 with placebo over 24 weeks. The amended design is expected to enrol approximately 970 participants across around 350 sites globally, with participants randomised in a 1:1:1 ratio.

The trial is evaluating adults aged 40 years and older with documented COPD and a history of at least two moderate or one severe exacerbation in the previous 12 months. Participants must also be receiving stable inhaled dual or triple maintenance therapy.

The primary endpoint is the annualised rate of moderate or severe COPD exacerbations over the 24-week treatment period.

Targeting IRAK4 inflammation pathways

AZD6793 is an oral inhibitor of interleukin-1 receptor-associated kinase 4 (IRAK4), a protein involved in signalling from several inflammatory pathways.

The drug is being developed to interfere with signalling involving interleukin-1, interleukin-18, interleukin-36, interleukin-33 and toll-like receptors. These pathways are involved in inflammatory responses in the lungs.

The Phase 2b study will assess whether inhibiting IRAK4 can reduce exacerbations in people with COPD who remain at risk despite maintenance treatment.

Earlier Phase 1 research evaluated AZD6793 in healthy volunteers and people with COPD. The study found no severe or serious adverse events, while target engagement was demonstrated through inhibition of inflammatory cytokine release.

Exacerbations are the key measure

PRESTO will assess whether AZD6793 can reduce the frequency of moderate and severe COPD exacerbations rather than relying only on measures of lung function or inflammatory activity.

Secondary endpoints include time to the first exacerbation, severe exacerbations, healthcare-intensive exacerbations, lung function, pharmacokinetics, patient-reported outcomes and safety.

The trial is currently recruiting, with AstraZeneca estimating primary completion in November 2027.

The development of AZD6793 comes as AstraZeneca also advances other approaches to COPD treatment. The company recently reported positive Phase 3 results for tozorakimab, an IL-33-targeting antibody, in the OBERON and TITANIA trials, with reductions in moderate and severe COPD exacerbations reported across a broad patient population.

No Phase 2b efficacy results for AZD6793 are currently available. The PRESTO trial will therefore provide the first substantial test of whether IRAK4 inhibition can translate into a reduction in COPD exacerbations in a larger patient population.