Maribavir for Refractory or Resistant Cytomegalovirus Infections in Hematopoietic-cell or Solid-organ Transplant Recipients: A Randomized, Dose-ranging, Double-blind, Phase 2 Study

Clin Infect Dis. 2019 Apr 8;68(8):1255-1264. doi: 10.1093/cid/ciy706.


Background: Cytomegalovirus (CMV) infections that are refractory or resistant (RR) to available antivirals ([val]ganciclovir, foscarnet, cidofovir) are associated with higher mortality in transplant patients. Maribavir is active against RR CMV strains.

Methods: Hematopoietic-cell or solid-organ transplant recipients ≥12 years old with RR CMV infections and plasma CMV deoxyribonucleic acid (DNA) ≥1000 copies/mL were randomized (1:1:1) to twice-daily dose-blinded maribavir 400, 800, or 1200 mg for up to 24 weeks. The primary efficacy endpoint was the proportion of patients with confirmed undetectable plasma CMV DNA within 6 weeks of treatment. Safety analyses included the frequency and severity of treatment-emergent adverse events (TEAEs).

Results: From July 2012 to December 2014, 120 patients were randomized and treated (40 per dose group): 80/120 (67%) patients achieved undetectable CMV DNA within 6 weeks of treatment (95% confidence interval, 57-75%), with rates of 70%, 63%, and 68%, respectively, for maribavir 400, 800, and 1200 mg twice daily. Recurrent on-treatment CMV infections occurred in 25 patients; 13 developed mutations conferring maribavir resistance. Maribavir was discontinued due to adverse events in 41/120 (34%) patients, and 17/41 discontinued due to CMV infections. During the study, 32 (27%) patients died, 4 due to CMV disease. Dysgeusia was the most common TEAE (78/120; 65%) and led to maribavir discontinuation in 1 patient. Absolute neutrophil counts <1000/µL were noted in 12/106 (11%) evaluable patients, with rates similar across doses.

Conclusions: Maribavir ≥400 mg twice daily was active against RR CMV infections in transplant recipients; no new safety signals were identified.

Clinical trials registration: NCT01611974.

Keywords: cytomegalovirus; foscarnet; ganciclovir; maribavir; transplantation.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antiviral Agents / administration & dosage*
  • Benzimidazoles / administration & dosage*
  • Cytomegalovirus Infections / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Resistance, Viral
  • Female
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunocompromised Host*
  • Male
  • Ribonucleosides / administration & dosage*
  • Transplant Recipients
  • Young Adult


  • Antiviral Agents
  • Benzimidazoles
  • Ribonucleosides
  • maribavir

Associated data