Treatment for First Cytomegalovirus Infection Post-Hematopoietic Cell Transplant in the AURORA Trial: A Multicenter, Double-Blind, Randomized, Phase 3 Trial Comparing Maribavir with Valganciclovir

Background. Neutropenia may limit use of valganciclovir treatment for cytomegalovirus (CMV) infection following hematopoietic cell transplant (HCT). A phase 2 study indicated efficacy of maribavir with fewer treatment-limiting toxicities than valganciclovir. Methods. In this multicenter, double-blind, phase 3 study, patients with first asymptomatic CMV infection post-HCT were stratified and randomized 1:1 to maribavir 400 mg twice daily or valganciclovir (dose-adjusted for renal clearance) for 8 weeks with 12 weeks follow-up. Primary T endpoint was confirmed CMV viremia clearance at week 8 (primary hypothesis of noninferiority margin of 7.0%). Key secondary endpoint was a composite of the primary endpoint IP with no findings of CMV tissue-invasive disease at week 8, through week 16. Treatmentemergent adverse events (TEAEs) were assessed. R Results. Among patients treated (273 maribavir; 274 valganciclovir), the primary endpoint of C non-inferiority of maribavir was not met (maribavir, 69.6%; valganciclovir, 77.4%; adjusted S difference [95% confidence interval (CI)]: −7.7% [−14.98, −0.36]; lower limit of 95% CI of treatment difference exceeded −7.0%). At week 16, 52.7% and 48.5% of patients treated U (maribavir and valganciclovir, respectively) maintained CMV viremia clearance without tissueinvasive disease (adjusted difference [95% CI]: 4.4% [−3.91, 12.76]). With maribavir (versus N valganciclovir), fewer patients experienced neutropenia (16.1% and 52.9%) or discontinued due A to TEAEs (27.8% and 41.2%). Discontinuations were mostly due to neutropenia (maribavir, M 4.0%; valganciclovir, 17.5%). Conclusions. Although non-inferiority of maribavir to valganciclovir for the primary endpoint was not achieved based on the prespecified non-inferiority margin, maribavir demonstrated comparable CMV viremia clearance during post-treatment follow-up, with fewer D discontinuations due to neutropenia.