Dose-dependent efficacy of intravenous brincidofovir across adenovirus species in immunocompromised patients

OBJECTIVES: Invasive infections caused by different human adenovirus (HAdV) species represent a life-threatening complication in immunocompromised patients, but no approved antiviral treatment is currently available. METHODS: Using PCR-based screening and next-generation sequencing (NGS), we monitored immunocompromised patients with invasive HAdV infection (n=31) enrolled in the phase 2a ATHENA trial, which evaluated optimal dosing regimens of intravenous brincidofovir (BCV). RESULTS: Molecular typing of blood and stool specimens revealed the presence of nearly all HAdV species (A-F), including both common and rarely observed genotypes. Quantitative viral load monitoring indicated sustained clearance of any HAdV species from peripheral blood within five weeks of treatment in the patient cohort treated with the BCV dosing regimen identified as optimal (0.4mg/kg twice weekly). CONCLUSIONS: These findings support a dose-dependent broad efficacy of intravenous BCV across all relevant HAdV species and set the stage for an ensuing phase 3 trial, facilitating future regulatory approval of the compound for this urgently needed indication.