On 19 May 2025 at the American Thoracic Society (ATS) International Conference held in San Francisco, AstraZeneca presented results from a Phase II proof-of-concept trial evaluating its bispecific monoclonal antibody, gremubamab, against Pseudomonas aeruginosa infection in patients with bronchiectasis. Results demonstrated the ability of gremubamab to reduce the bacterial load of pseudomonas and improve quality of life for these patients. The findings highlight the ability of gremubamab to act as a targeted therapy against bacterial infection, with the possible potential to reduce reliance on antibiotics in bronchiectasis patients.
The Phase II proof-of-concept trial (GREAT-2; [ISRCTN Number ISRCTN70034823]) enrolled 37 participants with CT-confirmed bronchiectasis and sputum positive for P. aeruginosa. Participants were randomized 1:1:1 to 500mg (n=13) or 1,500mg (n=12) gremubamab intravenous infusion, or placebo (n=12), once every four weeks for 12 weeks. Results at the end-of-treatment period (day 84) demonstrated a significant reduction ([estimate[80%CI]]; -1.25 log-CFU (-2.33 to -0.16); 1-sided p=0.071) in bacterial load in the 500mg arm versus placebo, while a lesser reduction was observed in the 1,500mg arm (-0.66(-1.71 to 0.39); p=0.2). Additionally, improvements in patient-reported outcome measures were observed in the active treatment arms; 38.5% of participants in the 500mg arm and 41.7% of participants in the 1,500mg arm achieved clinically significant improvements in St. George’s Respiratory Questionnaire (SGRQ) versus 8.3% in the placebo arm. Positive signals were also observed in multiple domains of the Quality-of-Life Questionnaire – Bronchiectasis (QoL-B). While no effect on FEV1 was observed, time to first exacerbation was significantly prolonged in the 1,500mg arm versus placebo (p=0.046). Incidence rates for adverse events (AEs) and severe AEs were similar between the gremubamab and placebo arms.
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Gremubamab’s positive set of results offers an encouraging outlook for the treatment of bacterial infections in bronchiectasis patients. Bacterial load is a factor that can increase the risk of exacerbations. Current strategies to tackle bacterial infection include prolonged use of antibiotics – a mainstay treatment within bronchiectasis – but long-term antibiotics use carries the risk of resistance and side effects, representing a gap in the market for a targeted therapy option and an alternative to antibiotics to address bacterial infections in bronchiectasis patients.
It is precisely this gap to which gremubamab can potentially cater. If results from late-stage clinical trials can reproduce a set of results such as those of the GREAT-2 trial, it could represent a paradigm shift in the treatment of bacterial infections within bronchiectasis and within the wider respiratory space.
