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Abstract: TH-OR57

Phase 3 Study of Maribavir (MBV) vs. Investigator-Assigned Therapy (IAT) for Refractory/Resistant (R/R) Cytomegalovirus (CMV) Infection Post-Transplant: Analysis of Kidney Recipients and Renal Safety

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Shihab, Fuad S., University of Utah Health Care, Salt Lake City, Utah, United States
  • Avery, Robin K., Johns Hopkins University Division of Infectious Diseases, Baltimore, Maryland, United States
  • Blumberg, Emily, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Haririan, Abdolreza, University of Maryland, Baltimore, Maryland, United States
  • Wu, Jingyang, Shire Human Genetic Therapies, Inc., a Takeda company, Lexington, Massachusetts, United States
  • Sundberg, Aimee K., Shire Human Genetic Therapies, Inc., a Takeda company, Lexington, Massachusetts, United States
Background

Risk of nephrotoxicity limits antiviral use for treatment (tx) of transplant recipients with CMV infection. We report efficacy (including sub-analysis of kidney recipients) and renal safety data from a phase 3 study of MBV vs IAT in patients (pts) with R/R CMV infection (NCT02931539).

Methods

Transplant recipients (≥12y) with CMV infection (screening plasma DNA≥910IU/mL) R/R to prior tx (failure to achieve>1log10 decrease in CMV DNA after≥14days±genotyped resistance) were randomized 2:1 MBV (400mg BID):IAT (val/ganciclovir,foscarnet[FOS],cidofovir) for 8wks. Primary endpoint:confirmed CMV clearance at end of Wk8 (plasma DNA<137IU/mL in 2 consecutive tests≥5days apart). Key secondary endpoint:CMV clearance and symptom control at end of Wk8 maintained through Wk16. Group differences were adjusted for baseline CMV DNA level+solid organ/hematopoietic cell transplant where applicable. Subgroup analysis of kidney recipients was conducted. Tx-emergent adverse events (TEAEs) were assessed (safety set).

Results

More MBV (randomized set: 235 MBV, 117 IAT[47 FOS]) pts achieved the primary (55.7% vs 23.9% IAT; adjusted difference[AD] 32.8%, 95%CI 22.8–42.7;p<0.001) and key secondary endpoint (18.7% vs 10.3% IAT; AD 9.5%, 95%CI 2.0–16.9;p=0.013). For kidney recipients (74 MBV, 32 IAT), 59.5% MBV vs 34.4% IAT pts achieved CMV clearance (AD 26.7%, 95%CI 7.5–45.9). Rates of TEAEs were similar between MBV and IAT (Table). Dysgeusia was the most frequent TEAE with MBV (37.2%, IAT 3.4% pts). Tx-related TEAE of increased immunosuppressant drug level was reported in 6%pts treated with MBV (IAT 0%pts). Renal and urinary TEAE rates were lower for MBV (17.1%pts) than IAT (26.7%pts[FOS 44.7%pts]). A lower proportion of pts had tx-related acute kidney injury (AKI) with MBV (1.7%) than IAT (7.8%[FOS 19.1%]). Pts in the IAT arm discontinued tx due to AKI (5.2%[FOS 12.8%]); no pts treated with MBV discontinued tx due to renal TEAEs.

Conclusion

Maribavir was superior to IAT for achievement of clearance of R/R CMV infection among transplant recipients, with consistent benefit in kidney recipients. Rates of renal TEAEs were lower with MBV than IAT.

Overall and renal TEAEs and tx-related TEAEs occurring in ≥5% of patients in the MBV or IAT arms (safety set)
n (%) of patientsTEAETx-related TEAE
MBV
(n=234)
IAT
(n=116)
MBV
(n=234)
IAT
(n=116)
Any TEAE or tx-related TEAE

Any renal and urinary TEAEa

Acute kidney injuryb
228 (97.4)

40 (17.1)

20 (8.5)
106 (91.4)

31 (26.7)

11 (9.5)
141 (60.3)

4 (1.7)

4 (1.7)
57 (49.1)

15 (12.9)

9 (7.8)
aSystem organ class. Included adverse events coded using MedDRA, version 23.0; bPreferred term.
IAT, Investigator-assigned therapy; MBV, maribavir; TEAE, treatment-emergent adverse event; tx, treatment.

Funding

  • Commercial Support