2287. Maribavir Versus Valganciclovir for Preemptive Treatment of Cytomegalovirus (CMV) Viremia: A Randomized, Dose-Ranging, Phase 2 Study Among Hematopoietic Stem Cell Transplant (SCT) and Solid Organ Transplant (SOT) Recipients
Session: Poster Abstract Session: Transplants: CMV and Transplantation
Saturday, October 29, 2016
Room: Poster Hall

Background: CMV is associated with morbidity and mortality among SCT and SOT recipients. Current anti-CMV therapy is associated with side effects including myelosuppression and renal toxicity. Maribavir (MBV) is a potent and selective orally bioavailable anti-CMV agent. This Phase 2 study (EudraCT 2010-024247-32) assessed safety, tolerability and anti-CMV activity of preemptive MBV versus valganciclovir (VGC) among hematopoietic SCT or SOT recipients.

Methods: SCT/SOT recipients aged ≥18 years with 1000–100,000 CMV DNA copies/mL in blood/plasma and no documented CMV organ disease were randomized 1:1:1:1 to receive oral MBV 400, 800 or 1200 mg twice daily (BID), or VGC (Weeks 1–3: 900 mg BID, after Week 3: 900 mg once daily; adjusted for renal function), for up to 12 weeks. Primary safety analysis focused on incidence of treatment-emergent adverse events (TEAEs). Primary efficacy endpoint was proportion of patients with confirmed undetectable plasma CMV DNA within 3 and 6 weeks of treatment (‘responders’). Treatment effect estimates were calculated for the pooled MBV group versus VGC and compared statistically; no statistical tests were performed on safety endpoints.

Results: Between May 2012 and July 2014, 159/161 randomized patients received study drug (119 MBV [58 SOT], 40 VGC [19 SOT]); median (range) age 58 (18–76) years. Efficacy results are shown in the table.

Most TEAEs were mild–moderate in severity. Gastrointestinal AEs (nausea/vomiting/diarrhea) occurred more frequently in those receiving MBV (20–23%) versus VGC (10–15%); dysgeusia occurred more frequently with MBV (40%) versus VGC (3%) but with no apparent dose effect. Neutropenia (ANC <1000/mm3) occurred less frequently with MBV (5%) versus VGC (18%).

Conclusion: MBV 400–1200 mg BID had similar efficacy to VGC at clearing CMV viremia among SCT/SOT recipients, with a similar treatment effect across MBV doses. MBV was generally well tolerated with a safety profile similar to previous studies.

Johan Maertens, MD, PhD1, Catherine Cordonnier, MD2, Peter Jaksch, MD3, Xavier Poiré, MD4, Jingyang J Wu, MS5, Anna Wijatyk, MD5, Faouzi Saliba, MD6, Oliver Witzke, MD7 and Stephen Villano, MD8, (1)UZ Leuven, Leuven, Belgium, (2)Henri Mondor Hospital and University Paris-Est-Créteil, Créteil, France, (3)Medical University of Vienna, Vienna, Austria, (4)Cliniques Universitaires Saint-Luc, Brussels, Belgium, (5)Shire, Lexington, MA, (6)AP-HP Hôpital Paul Brousse, Villejuif, France, (7)University Hospital Essen, Essen, Germany, (8)Shire (at time of study), Wayne, PA

Disclosures:

J. Maertens, None

C. Cordonnier, None

P. Jaksch, None

X. Poiré, None

J. J. Wu, Shire: Employee , Salary

A. Wijatyk, Shire: Employee , Salary and Stock

F. Saliba, Viropharma: Investigator and Scientific Advisor , Speaker honorarium

O. Witzke, None

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

Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.