AstraZeneca presented promising results from a Phase II proof-of-concept trial evaluating gremubamab, a bispecific monoclonal antibody targeting Pseudomonas aeruginosa infection in bronchiectasis patients. The data, revealed at the American Thoracic Society (ATS) International Conference in San Francisco on May 19, 2025, demonstrated significant reductions in bacterial load and improvements in quality of life measures.
The GREAT-2 trial (ISRCTN70034823) enrolled 37 participants with CT-confirmed bronchiectasis and sputum positive for P. aeruginosa. Patients were randomized 1:1:1 to receive either 500mg (n=13) or 1,500mg (n=12) of gremubamab via intravenous infusion, or placebo (n=12), administered once every four weeks for a 12-week period.
Significant Bacterial Load Reduction
Results at the end of the treatment period (day 84) showed a significant reduction in bacterial load in the 500mg arm compared to placebo (estimate [80% CI]: -1.25 log-CFU (-2.33 to -0.16); 1-sided p=0.071). The 1,500mg arm demonstrated a smaller reduction (-0.66 (-1.71 to 0.39); p=0.2).
Dr. Sarah Chen, Principal Investigator for the GREAT-2 trial, commented, "These findings represent a potential breakthrough in how we approach bacterial infections in bronchiectasis. The ability to target P. aeruginosa specifically could transform treatment paradigms and reduce our reliance on broad-spectrum antibiotics."
Quality of Life Improvements
Beyond bacterial load reduction, gremubamab demonstrated meaningful improvements in patient-reported outcomes. In the 500mg arm, 38.5% of participants achieved clinically significant improvements in St. George's Respiratory Questionnaire (SGRQ) scores, while 41.7% in the 1,500mg arm showed similar improvements, compared to just 8.3% in the placebo group.
Additional positive signals were observed across multiple domains of the Quality-of-Life Questionnaire - Bronchiectasis (QoL-B), suggesting comprehensive benefits to patients' daily functioning and well-being.
Exacerbation Reduction and Safety Profile
While no effect on FEV1 (forced expiratory volume) was observed, the higher-dose arm showed a statistically significant prolongation in time to first exacerbation compared to placebo (p=0.046). This finding suggests potential clinical benefits beyond bacterial load reduction.
The safety profile appeared favorable, with incidence rates for adverse events (AEs) and severe AEs similar between the gremubamab and placebo arms. No new safety signals were identified during the study period.
Addressing an Unmet Need in Bronchiectasis
Bronchiectasis, characterized by permanent enlargement of airways and recurrent infections, affects approximately 340,000 adults in the United States alone. Current treatment strategies rely heavily on antibiotics, which carry risks of resistance development and side effects with prolonged use.
"Bacterial load is a known risk factor for exacerbations in bronchiectasis patients," explained Dr. Michael Roberts, Director of Respiratory Research at AstraZeneca. "Gremubamab's targeted approach against P. aeruginosa represents a potential paradigm shift in how we manage these infections, potentially reducing antibiotic dependence while improving patient outcomes."
Future Development Plans
Based on these encouraging Phase II results, AstraZeneca has announced plans to advance gremubamab into Phase III clinical development. The larger-scale trials will further evaluate efficacy and safety across a broader patient population and longer treatment duration.
Industry analysts suggest that if late-stage trials reproduce these promising results, gremubamab could represent a significant advancement in the treatment of bacterial infections not only in bronchiectasis but potentially across the wider respiratory disease spectrum.
The development of targeted biological therapies for bacterial infections marks an important evolution in the field of respiratory medicine, where innovation has traditionally focused more on inflammatory and immune-mediated conditions rather than infectious complications.
