Cytomegalovirus prophylaxis with letermovir in pediatric (birth to <18 years of age) hematopoietic cell transplant recipients: pharmacokinetics, efficacy, and safety results of a Phase 2b study

Letermovir, a cytomegalovirus (CMV) terminase complex inhibitor, was first approved for prophylaxis of CMV infection and disease in adult CMV-seropositive allogeneic hematopoietic cell transplant (HCT) recipients (R+). This study evaluated the pharmacokinetics (PK), efficacy, and safety of letermovir in pediatric R+ allogeneic HCT recipients. In this Phase 2b, single-arm, open-label study, 65 participants were enrolled sequentially in three age groups (AG; AG1, 12 to <18 years; AG2, 2 to <12 years; and AG3, birth to <2 years). PK was evaluated in an initial cohort in each AG using intensive PK data to confirm or modify dosing before enrolling the remaining participants. Adult HCT population PK (PopPK) data were used to establish the exposure reference range. The adult letermovir dose evaluated in AG1 and AG2 participants achieved exposures generally within the adult HCT reference range. In AG3, the initial cohort (letermovir with cyclosporin A) achieved exposures trending lower than the median exposure target; the letermovir dose was increased for the remaining participants. Efficacy and safety in pediatric participants were generally consistent with adult HCT data. A pediatric HCT PopPK model was developed to determine dose recommendations to be included in patient prescribing information. The doses evaluated achieved exposures generally within the adult HCT reference range. At exposures achieved, letermovir was efficacious and safe in preventing clinically significant CMV infection in pediatric allogeneic HCT recipients. The observed concentration data informed a pediatric PopPK model to optimize final letermovir dose recommendations in this population. CLINICAL TRIALS This study is registered with ClinicalTrials.gov as NCT03940586 .