Clinical Pharmacology of Maribavir (SHP620): A Comprehensive Overview

Abstract

Introduction Maribavir, a potent and orally bioavailable antiviral, is being evaluated in Phase 3 trials for the treatment of CMV infections in transplant patients and received FDA Breakthrough Therapy designation. A thorough understanding of the clinical pharmacology of maribavir is necessary to guide the appropriate use of the drug in transplant patients who often have multiple comorbidities and require complex concurrent medication regimens. Objectives To summarize the clinical pharmacology data of maribavir. Methods Pharmacokinetic and pharmacodynamic assessments were performed in sixteen Phase 1 studies and three Phase 2 studies. Data were summarized to characterize maribavir's disposition (absorption, distribution, metabolism, and excretion) in healthy adult subjects and special populations (HIV-infected, hepatically impaired, renally impaired, and organ transplant recipients). A definitive QT study was conducted to evaluate the cardiac repolarization effect. The drug interaction risks were assessed using both nonclinical and clinical studies. Results Maribavir is primarily eliminated through the CYP3A4 pathway and has a half-life of 5–7 hours. Co-administration with food or antacid, or crushing the tablet, had no impact on maribavir's exposure. Maribavir binds to plasma proteins with unbound fraction estimated at 1.5% and can penetrate the blood–retinal barrier. No pharmacokinetic difference is found among healthy subjects, transplant patients, subjects with severe renal impairment, or moderate hepatic impairment. Maribavir's exposure is increased by 46% by ketoconazole and decreased by 61% by rifampin. Maribavir increases tacrolimus exposure by 51%, does not affect voriconazole exposure, and is not expected to affect exposures of most other concurrent medications. Maribavir has no effects on QT intervals. Conclusions Extensive clinical pharmacology data have been generated to support the clinical use and dose of maribavir for the treatment of CMV infections in transplant recipients. Maribavir can be taken with or without food. No maribavir dose adjustment is needed in patients with mild-to-moderate hepatic impairment or renal impairment or with concurrent medications, except for CYP3A4 inducers.