Preemptive treatment of Cytomegalovirus infection in kidney transplant recipients with letermovir: results of a Phase 2a study |
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Authors: | Susanne Stoelben Wolfgang Arns Lutz Renders Jürgen Hummel Anja Mühlfeld Manfred Stangl Michael Fischereder Wilfried Gwinner Barbara Suwelack Oliver Witzke Michael Dürr Dietrich W Beelen Detlef Michel Peter Lischka Klemens Budde |
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Institution: | 1. AiCuris GmbH & Co. KG, Wuppertal, Germany;2. Transplantationszentrum, Kliniken der Stadt K?ln, Klinikum Merheim, Germany;3. Department of Nephrology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany;4. PPD, Bellshill, UK;5. Department of Nephrology and Clinical Immunology, University Clinic of the RWTH Aachen University, Aachen, Germany;6. Chirurgische Klinik und Poliklinik der TU München, Klinikum rechts der Isar, München, Germany;7. Schwerpunkt Nephrologie, Klinik und Poliklinik für Innere Medizin I – Campus Grosshadern, München, Germany;8. Department of Nephrology, Medical School Hannover, Hannover, Germany;9. Transplantationszentrum, Universit?tsklinikum Münster, Münster, Germany;10. Klinik für Nephrologie, Universit?tsklinikum Essen, Essen, Germany;11. Department of Nephrology, Charité Universit?tsmedizin Berlin, Berlin, Germany;12. Klinik für Knochenmarkstransplantation, Universit?tsklinikum Essen, Essen, Germany;13. Institut für Virologie, Universit?tsklinikum Ulm, Ulm, Germany;14. AiCuris GmbH & Co. KG, Wuppertal, GermanyThese two authors contributed equally to this study.
Dr. rer. nat. Holger Zimmermann, AiCuris GmbH & Co. KG, Friedrich Ebert Stra?e 475, 42117 Wuppertal, Germany.;15. Tel.: +49 202 31763 1176;16. fax: +49 202 31763 1177;17. e‐mail: Holger.Zimmermann@AiCuris.com |
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Abstract: | Cytomegalovirus (CMV) infection remains a significant cause of morbidity and mortality in transplant recipients. Letermovir (AIC246), is a novel anti‐HCMV drug in development, acting via a novel mechanism of action. In this proof‐of‐concept trial with first administration of letermovir to patients, 27 transplant recipients with active CMV replication were randomly assigned to a 14‐day oral treatment regimen of either letermovir 40 mg twice a day, letermovir 80 mg once a day, or local standard of care (SOC) in a multicenter, open‐label trial. Efficacy, safety, and limited pharmacokinetic parameters were assessed. All groups had a statistically significant decrease in CMV‐DNA copy number from baseline (40 mg BID: P = 0.031; 80 mg QD: P = 0.018; SOC: P = 0.001), and comparison of viral load reduction between treatment groups showed no statistically significant differences. Viral clearance was achieved for 6 of 12 patients (50%) in the letermovir groups versus two of seven SOC patients (28.6%). Letermovir treatment was generally well tolerated, no patient developed CMV disease during the trial. Both letermovir treatment regimens resulted in equally high trough level plasma concentrations. The efficacy, safety, and pharmacokinetics observed in these viremic transplant recipients indicate that letermovir is a promising new anti‐CMV drug. |
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Keywords: | AIC246 human cytomegalovirus kidney transplantation letermovir preemptive therapy |
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