78. Maribavir for Treatment of Cytomegalovirus (CMV) Infections Resistant or Refractory to Ganciclovir or Foscarnet in Hematopoietic Stem Cell Transplant (SCT) or Solid Organ Transplant (SOT) Recipients: A Randomized, Dose-Ranging, Double-Blind, Phase 2 Study
Session: Oral Abstract Session: Infections in Transplantation
Thursday, October 27, 2016: 8:30 AM
Room: 388-390
Background: CMV infection resistant or refractory to standard therapy is associated with substantial morbidity and mortality amongtransplant recipients. Approved anti-CMV therapies are associated with adverse effects including myelosuppression, nephrotoxicity and electrolyte imbalances. Maribavir (MBV) is active in vitro against CMV strains resistant to other agents. This Phase 2 study (NCT01611974) assessed the safety, tolerability and antiviral activity of MBV for treatment of resistant or refractory CMV infections among SCT and SOT recipients.
Methods: SCT/SOT recipients aged ≥12 years with CMV infection (≥1000 DNA copies/mL in blood/plasma) resistant or refractory to (val)ganciclovir or foscarnet were randomized 1:1:1 to receive oral MBV 400, 800 or 1200 mg twice daily (BID), for up to 24 weeks. Primary safety analysis focused on incidence of treatment-emergent adverse events (TEAEs). Primary efficacy endpoint was the proportion of patients with confirmed undetectable plasma CMV DNA within 6 weeks’ treatment. Secondary endpoints included the proportion of patients with plasma CMV DNA recurrence during the study.
Results: From July 2012 to December 2014, 120 patients were randomized (47 SCT, 73 SOT; 40/dose group); median age 55 (range 18–74) years. At baseline, 17/106 (16%) patients had neutropenia (ANC <1000/mm3). Efficacy results are shown in the table. MBV was discontinued due to an AE in 41/120 (34%) patients; 17/41 due to CMV infection. Dysgeusia was the most common TEAE (Table) and led to MBV discontinuation in 1 patient. Neutropenia occurred in 12/106 (11%) patients; rates similar across doses.
Conclusion: MBV 400–1200 mg BID was effective for treatment of CMV infection resistant/refractory to standard therapy among SCT/SOT recipients. There was no evidence of myelosuppression; data support the safety of MBV administered for up to 24 weeks. Further development of MBV for CMV treatment is warranted.

Genovefa Papanicolaou, MD1, Fernanda P. Silveira, MD2, Amelia Langston, MD3, Marcus R. Pereira, MD, MPH4, Robin Avery, MD, FIDSA5, Anna Wijatyk, MD6, Jingyang J Wu, MS6, Michael Boeckh, MD, FIDSA7, Francisco M. Marty, MD, FIDSA8 and Stephen Villano, MD9, (1)Infectious Diseases, Memorial Sloan Kettering Cancer Center, New York, NY, (2)University of Pittsburgh Medical Center, Pittsburgh, PA, (3)Winship Cancer Institute, Atlanta, GA, (4)Division of Infectious Diseases, Columbia University Medical Center, New York, NY, (5)Johns Hopkins University, Baltimore, MD, (6)Shire, Lexington, MA, (7)Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, (8)Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, (9)Shire (at time of study), Wayne, PA

Disclosures:

G. Papanicolaou, Shire: Investigator , Research support

F. P. Silveira, Shire: Investigator , Research support
Viropharma: Investigator , Research support

A. Langston, None

M. R. Pereira, None

R. Avery, Shire: Investigator , Research support
Astellas: Investigator , Research support
Merck: Investigator , Research support
Chimerix: Investigator , Research support
Oxford Immunotec: Investigator , Research support

A. Wijatyk, Shire: Employee , Salary and Stock

J. J. Wu, Shire: Employee , Salary

M. Boeckh, Merck: Consultant and Investigator , Consulting fee and Research support
Shire: Consultant , Consulting fee
Chimerix: Consultant and Investigator , Consulting fee and Research support
Astellas: Consultant and Investigator , Consulting fee and Research support
Microbiotix: Consultant , Consulting fee
Clinigen: Consultant , Consulting fee

F. M. Marty, Alexion: Scientific Advisor , Consulting fee
Ansun: Investigator , Research support
Astellas: Consultant and Investigator , Consulting fee and Research support
Basilea: Conference speaker , Speaker honorarium
Chimerix: Consultant and Investigator , Consulting fee and Research support
Gilead: Consultant and Investigator , Consulting fee and Research support
GlaxoSmithKline: Consultant and Investigator , Consulting fee and Research grant
LFB, S.A.: Consultant , Consulting fee
Merck: Consultant and Investigator , Consulting fee and Research support
Shire: Consultant and Investigator , Consulting fee and Research support
WHISCON: Investigator , Research support
Pfizer: Course speaker , Speaker honorarium
Fate Therapeutics: Scientific Advisor , Consulting fee

S. Villano, Shire (at time of study): Employee , Salary

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