On November 23, the U.S. Food and Drug Administration (FDA) approved the antiviral maribavir (Livtencity) for adult and pediatric patients aged 12 years and older (and weighing at least 35 kg) with posttransplant cytomegalovirus (CMV) infection or disease that is not responsive (with or without genetic mutations that cause resistance) to available antiviral treatment for CMV. Maribavir works by preventing the activity of the human cytomegalovirus enzyme pUL97, thus blocking virus replication.
“Transplant recipients are at a much greater risk for complications and death when faced with a cytomegalovirus infection,” said John Farley, MD, MPH, Director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research. “Cytomegalovirus infections that are resistant or do not respond to available drugs are of even greater concern. [This] approval helps meet a significant unmet medical need by providing a treatment option for this patient population.”
CMV is a type of herpes virus that commonly causes infection in patients after a stem cell or organ transplant. CMV infection can lead to CMV disease and have a major negative impact on transplant recipients, including loss of the transplanted organ and death.
Maribavir’s safety and efficacy were evaluated in a phase III, multicenter, open-label, active-controlled trial (ClinicalTrials.gov identifier: NCT02931539) that compared maribavir with investigator’s choice of treatment, which could include one or two of the following antivirals used to treat CMV: ganciclovir, valganciclovir, foscarnet, or cidofovir. In the study, 352 transplant recipients with CMV infections who did not respond (with or without resistance) to treatment randomly received maribavir or investigator’s choice of treatment for up to 8 weeks.
The study compared the two groups’ plasma CMV DNA concentration levels at the end of the study’s eighth week, with efficacy defined as having a level below what is measurable. Of the 235 patients who received maribavir, 56% had levels of CMV DNA below what was measurable vs 24% of the 117 patients who received an investigator-assigned treatment.
The most common side effects of treatment with maribavir included taste disturbance, nausea, diarrhea, vomiting, and fatigue. Maribavir may reduce the antiviral activity of ganciclovir and valganciclovir, so coadministration with these drugs is not recommended. Virologic failure due to resistance can occur during and after treatment with maribavir; therefore, CMV DNA levels should be monitored and maribavir resistance should be checked if the patient is not responding to treatment or relapses.
Maribavir received Breakthrough Therapy and Priority Review designations for this indication.