Preemptive treatment of Cytomegalovirus infection in kidney transplant recipients with letermovir: results of a Phase 2a study.

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.

• 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, Holger Zimmermann, Helga Rübsamen-Schaeff, Klemens Budde
• Journal: Transplant international : official journal of the European Society for Organ Transplantation (Transpl Int) Vol. 27 Issue 1 Pg. 77-86 (Jan 2014) ISSN: 1432-2277 [Electronic] Switzerland
• PMID: 24164420 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.

Chemical References

• Acetates
• Antiviral Agents
• DNA, Viral
• Quinazolines
• letermovir

Topics

• Acetates (administration & dosage, pharmacokinetics)
• Adult
• Aged
• Antiviral Agents (administration & dosage, pharmacokinetics)
• Cytomegalovirus (genetics)
• Cytomegalovirus Infections (drug therapy, virology)
• DNA, Viral (blood)
• Female
• Humans
• Kidney Transplantation (adverse effects)
• Male
• Middle Aged
• Opportunistic Infections (drug therapy, virology)
• Quinazolines (administration & dosage, pharmacokinetics)
• Viral Load
• Viremia (virology)