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Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia

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Abstract

The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal antibody panobacumab was developed as an adjunctive immunotherapy for the treatment of O11 serotype Pseudomonas aeruginosa infections. We evaluated the potential clinical efficacy of panobacumab in the treatment of nosocomial pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics of panobacumab. Patients treated with panobacumab (n = 17), including 13 patients receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14 patients who did not receive the antibody. Overall, the 17 patients receiving panobacumab were more ill. They were an average of 72 years old [interquartile range (IQR): 64–79] versus an average of 50 years old (IQR: 30–73) (p = 0.024) and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 17 (IQR: 16–22) versus 15 (IQR: 10–19) (p = 0.043). Adjunctive immunotherapy resulted in an improved clinical outcome in the group receiving the full three-course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 % (9/14) (p = 0.048). The Kaplan–Meier survival curve showed a statistically significantly shorter time to clinical resolution in this group of patients (8.0 [IQR: 7.0–11.5] versus 18.5 [IQR: 8–30] days in those who did not receive the antibody; p = 0.004). Panobacumab adjunctive immunotherapy may improve clinical outcome in a shorter time if patients receive the full treatment (three doses). These preliminary results suggest that passive immunotherapy targeting LPS may be a complementary strategy for the treatment of nosocomial O11 P. aeruginosa pneumonia.

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Acknowledgments

We thank Holger Koch, Verena Gafner, and Michael P. Rudolf from Kenta Biotech, Schlieren, Switzerland for the development of panobacumab. Now ARIDIS Pharmaceuticals, San Jose, USA.

Author contributions

Y-AQ, J-LP, PE, and J-PR acquired patient data and prepared the manuscript.

J-PR performed the statistical analysis.

QL, J-JR, JC, MW, MT, EM, JG, BF, and P-FL acquired patient data.

AP, HL, and EM designed the study, and collected and analyzed the data from the original study.

Conflict of interest

The following authors declare that they have no competing interests: Jorge Garbino, Qin Lu, Jean-Jacques Rouby, Emmanuelle Mercier, Michael Tamm, Michel Wolff.

The following authors were employees of Kenta Biotech at the time of the trial and owned stocks of Kenta Biotech: Holger Koch, Hedvika Lazar, Erkan Mus, Michael P. Rudolf.

Jean Chastre has received consulting and/or lecture fees from Kenta Biotech, Pfizer, Brahms, Astellas, KaloBios, Sanofi, Nektar–Bayer, and Glaxo–Smith–Kline.

Philippe Eggimann has received consulting and/or lecture fees from Kenta Biotech, Pfizer, Astellas, KaloBios, and MSD. He was involved as a consultant for other Kenta Biotech projects.

Bruno François has received consulting and/or lecture fees in the last 3 years from Kenta Biotech, Sanofi, Talecris, GSK, and MedImmune.

Verena Gafner is a former employee of Kenta Biotech.

Pierre-Francois Laterre is a consultant at Kenta Biotech, Agennix, and AstraZeneca.

Antonio Perez is external Chief Medical Officer for Kenta Biotech. Now ARIDIS, Clinical Development Advisor.

Funding

The phase IIa study, but not this independent post-hoc analysis, was sponsored by Kenta Biotech AG. Now ARIDIS Pharmaceuticals, San Jose, USA.

Author information

Authors and Affiliations

  1. Adult Critical Care Service, Centre Hospitalier Universitaire Vaudois, CHUV, Rue du Bugnon 46, 1011, Lausanne, Switzerland

    Y.-A. Que, J.-L. Pagani, J.-P. Revelly & P. Eggimann

  2. Kenta Biotech, Schlieren, Switzerland

    H. Lazar, E. Mus & A. Perez

  3. Réanimation Médicale et Infectieuse, Hopital Bichat-Claude Bernard, AP-HP, Paris, France

    M. Wolff

  4. Intensive Care Unit, CIC-P 0801 Inserm, CHU Dupuytren, Limoges, France

    B. François

  5. Intensive Care Unit, Saint-Luc University Hospital, UCL, Brussels, Belgium

    P.-F. Laterre

  6. Service de Réanimation Polyvalente and CRICS Network, CHRU de Tours, Tours, France

    E. Mercier

  7. Infectious Diseases, University Hospitals of Geneva, Geneva, Switzerland

    J. Garbino

  8. Pneumonia Clinic, University Hospital Basel, Basel, Switzerland

    M. Tamm

  9. Réanimation Polyvalente, Département d’Anesthésie-Réanimation, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, UPMC Paris 6, Paris, France

    J.-J. Rouby & Q. Lu

  10. Service de Réanimation Médicale, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France

    J. Chastre

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  1. Y.-A. Que
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  2. H. Lazar
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  9. J.-P. Revelly
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  10. E. Mus
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  11. A. Perez
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  13. J.-J. Rouby
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Correspondence to P. Eggimann.

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Que, YA., Lazar, H., Wolff, M. et al. Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia. Eur J Clin Microbiol Infect Dis 33, 1861–1867 (2014). https://doi.org/10.1007/s10096-014-2156-1

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