Maribavir for refractory or resistant cytomegalovirus infections in hematopoietic-cell or solid-organ transplant recipients: A randomized, dose-ranging, double-blind, phase 2 study

Genovefa A. Papanicolaou, Fernanda P. Silveira, Amelia A. Langston, Marcus R. Pereira, Robin Avery, Marc Uknis, Anna Wijatyk, Jingyang Wu, Michael Boeckh, Francisco M. Marty, Stephen Villano

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1255-1264
Number of pages10
JournalClinical Infectious Diseases
Volume68
Issue number8
DOIs
StatePublished - Apr 8 2019

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Keywords

  • cytomegalovirus
  • foscarnet
  • ganciclovir
  • maribavir
  • transplantation

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Papanicolaou, G. A., Silveira, F. P., Langston, A. A., Pereira, M. R., Avery, R., Uknis, M., Wijatyk, A., Wu, J., Boeckh, M., Marty, F. M., & Villano, S. (2019). Maribavir for refractory or resistant cytomegalovirus infections in hematopoietic-cell or solid-organ transplant recipients: A randomized, dose-ranging, double-blind, phase 2 study. Clinical Infectious Diseases, 68(8), 1255-1264. https://doi.org/10.1093/cid/ciy706