title: 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.affiliation: AiCuris GmbH & Co. KG, Wuppertal, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Stoelben
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Arns
authors.forename: Lutz
authors.initials: L
authors.lastname: Renders
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hummel
authors.forename: Anja
authors.initials: A
authors.lastname: Mühlfeld
authors.forename: Manfred
authors.initials: M
authors.lastname: Stangl
authors.forename: Michael
authors.initials: M
authors.lastname: Fischereder
authors.forename: Wilfried
authors.initials: W
authors.lastname: Gwinner
authors.forename: Barbara
authors.initials: B
authors.lastname: Suwelack
authors.forename: Oliver
authors.initials: O
authors.lastname: Witzke
authors.forename: Michael
authors.initials: M
authors.lastname: Dürr
authors.forename: Dietrich W
authors.initials: DW
authors.lastname: Beelen
authors.forename: Detlef
authors.initials: D
authors.lastname: Michel
authors.forename: Peter
authors.initials: P
authors.lastname: Lischka
authors.forename: Holger
authors.initials: H
authors.lastname: Zimmermann
authors.forename: Helga
authors.initials: H
authors.lastname: Rübsamen-Schaeff
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
mesh_terms: D000085:Acetates / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D003587:Cytomegalovirus / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000188:drug therapy / Q000821:virology; D011799:Quinazolines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019562:Viral Load; D014766:Viremia / Q000821:virology
chemical_list: D000085:Acetates; D000998:Antiviral Agents; D004279:DNA, Viral; D011799:Quinazolines; C000588473:letermovir
keywords: AIC246; human cytomegalovirus; kidney transplantation; letermovir; preemptive therapy