A Bispecific Monoclonal Antibody Targeting Psl and PcrV for Chronic Pseudomonas Aeruginosa Infection in Patients With Bronchiectasis: Results From a Randomized, Double-Blind Placebo-Controlled Trial (GREAT-2)
Gremubamab in Bronchiectasis: A New Approach to Chronic Pseudomonas Aeruginosa Infection
Rationale:
Pseudomonas aeruginosa airway infection is associated with increased exacerbations and poor outcomes in bronchiectasis. Our prior study (GREAT-1) showed that gremubamab—a bivalent, bispecific mAb targeting Psl exopolysaccharide and PcrV T3SS component—enhanced neutrophil clearance of P. aeruginosa and reduced virulence ex-vivo.
Here we report the efficacy and safety of gremubamab in a proof-of-concept trial in bronchiectasis patients with P. aeruginosa infection.
Clinical Efficacy of Gremubamab in Bronchiectasis
Gremubamab treatment resulted in a significant reduction in bacterial load at EoT (day 84) with the 500mg dose compared with placebo treatment (-1.25 log-CFU (-2.33 to -0.16); p=0.071; ANCOVA), meeting the trial primary endpoint.
A non-significant directional trend was observed for the 1500mg dose (-0.66(-1.71 to 0.39); p=0.2).
The SGRQ was significantly improved versus placebo at EoT (500mg: -10.8; 1500mg: -12.1), and the proportion of patients achieving a clinically significant SGRQ improvement was higher for both gremubamab 500mg (38.5%) and 1500mg (41.7%) versus placebo (8.3%).
Clinically significant benefit in favour of gremubamab treatment at EoT was observed for multiple QoL-B domains.
Impact on Exacerbations and Pulmonary Function
Time to first exacerbation was significantly prolonged at the 1500mg dose versus placebo (p=0.046).
Conclusions – Proof of Concept for Targeted Monoclonal Antibody Therapy
Gremubamab treatment significantly reduced P. aeruginosa airway bacterial load and improved patient-reported quality of life in patients with bronchiectasis, providing proof-of-concept for specific anti-microbial monoclonal antibody therapy.
Authors
M.B. Long, R.C. Hull, A. Gilmour, K. Viligorska, H. Richardson, B.J.M. New, C. Hennayake, R. Galloway, E. Johnson, E. McIntosh, Z. Eke, H. Lind, M. Band, H. Bandara, G. Martin, S. Aliberti, A. Timothy, J. Norwell, J. Whitehouse, C.L. Addy, L. Finney, P. Mitchelmore, S.J. Caskey, R.W. Lord, A.T. Hill, M. Vendrell, E. Polverino, A. Marin, G. Suarez-Cuartin, M.R. Loebinger, M. Tunney, K. Cartwright, R. Hughes, A. Digiandomenico, M.G. Belvisi, W. Brailsford, C. Haworth, O. Sibila, J. Stobo, J.D. Chalmers
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Fecha de publicación
Published 2025, 19 May
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