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
- Kidney Transplantation: Breakthroughs from Basic to Translational to Clinical Research
November 04, 2021 | Location: Simulive, Virtual Only
Abstract Time: 04:30 PM - 06:00 PM
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 patients | TEAE | Tx-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 –