AstraZeneca’s AZD6793 holds potential to expand oral COPD treatment options, says GlobalData

At the European Respiratory Society (ERS) Congress 2026, AstraZeneca presented the design of the Phase IIb PRESTO trial, a large study set to evaluate whether AZD6793, an oral IRAK4 inhibitor, can reduce disease exacerbations in adults with moderate to very severe chronic obstructive pulmonary disease (COPD).

By targeting a shared signalling protein downstream of several inflammatory pathways, AZD6793 could offer a broad and convenient anti-inflammatory approach for patients who remain at risk despite stable inhaled treatment, says GlobalData, a leading intelligence and productivity platform.

AZD6793 inhibits IRAK4 downstream of IL-33/ST2, IL-1 beta, IL-18, IL-36, and toll-like receptor signalling, with the aim of modulating neutrophilic and eosinophilic inflammation and mucus production.

Eligible participants in the study are aged 40 years or older; have a post-bronchodilator FEV1 of 25% to less than 80% predicted and an FEV1/forced vital capacity ratio below 0.7; and have a recent exacerbation history while receiving stable inhaled therapy. The investigators note that a recent protocol amendment has reduced the initial submitted design from four arms and approximately 1,160 participants to two active-dose arms and one placebo arm, with approximately 970 participants randomized 1:1:1.

The primary endpoint is the annualized rate of moderate or severe COPD exacerbations over 24 weeks. Secondary measures include time to first exacerbation, severe and healthcare-intensive exacerbations, COPDCompEx events, pre- and post-bronchodilator lung function, pharmacokinetics, patient-reported outcomes, adverse events, and tolerability.

Graysen Vigneux, Immunology Analyst at GlobalData, comments: “PRESTO is an important clinical test because it moves IRAK4 inhibition beyond target engagement and into a large trial focused on exacerbations, a clear, real-world clinical outcome. A meaningful reduction on top of stable inhaled therapy would provide strong support for this upstream anti-inflammatory strategy.”

Reported Phase I data showed acceptable safety, pharmacokinetics, and pharmacodynamic target engagement in healthy participants and participants with COPD. The Phase IIb dose-ranging design is intended to identify a dose that provides sufficient pathway inhibition while retaining a safety profile suitable for chronic treatment.

Vigneux adds: “AZD6793 is differentiated by combining broad pathway coverage with oral administration. The practical advantage of an oral option could be valuable in COPD, but convenience will only matter if the study demonstrates a clear and durable clinical benefit without introducing limiting adverse effects.”

Patients with COPD can continue to experience exacerbations despite maintenance treatment. PRESTO directly addresses this residual risk through a clinically relevant primary endpoint, while its severe and healthcare-use measures should show whether any benefit extends to the events with the greatest consequences for patients and health systems.

Vigneux concludes: “Currently, PRESTO is active recruiting, and no Phase II efficacy results are available. The 24-week observation period, amended dose structure, and safety implications of inhibiting several innate immune pathways will be important when interpreting the findings. The trial must also demonstrate that any numerical reduction is both statistically reliable and clinically meaningful.”