The Food and Drug Administration (FDA) has approved Livtencity (maribavir) for the treatment of adults and pediatric patients (12 years of age and older and weighing at least 35kg) with post-transplant cytomegalovirus (CMV) infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir or foscarnet.
Livtencity is an orally bioavailable anti-CMV compound that targets and inhibits the UL97 protein kinase and its natural substrates. The approval was based on data from the multicenter, randomized, open-label, active-controlled phase 3 TAK-620-303 (SOLSTICE) trial (ClinicalTrials.gov: NCT02931539), which assessed the efficacy and safety of maribavir in 352 patients 12 years of age and older who were recipients of hematopoietic stem cell or solid organ transplant and were refractory or resistant to prior anti-CMV treatment.
Patients were randomly assigned 2:1 to receive either maribavir 400mg or conventional antiviral therapy orally for 8 weeks. Conventional antiviral therapy included an investigator assigned treatment of 1 or a combination of the following: ganciclovir, valganciclovir, foscarnet or cidofovir. The primary endpoint was the proportion of patients who achieved confirmed CMV viremia clearance at week 8, defined as plasma CMV DNA less than 137 IU/mL in 2 consecutive tests separated by at least 5 days.
Findings showed that 56% (n=131/235) of patients treated with maribavir achieved statistically superior confirmed CMV viremia clearance at week 8 compared with 24% (n=28/117) of those treated with conventional therapies (adjusted difference: 33%; 95% CI, 23-43; P <.001). Moreover, 19% of patients treated with maribavir achieved CMV DNA level less than lower limit of quantification and CMV infection symptom control at week 8 and maintained treatment effect through week 16 (secondary endpoint) vs 10% of those treated with conventional therapies (adjusted difference: 9%; 95% CI, 2-17; P =.013).
The treatment effect of maribavir was found to be consistent across transplant type, age group, and the presence of CMV syndrome/disease at baseline. However, maribavir was observed to be less effective in patients with increased CMV DNA levels (50,000 IU/mL or greater) and those with absence of genotypic resistance.
The most common adverse reactions reported with maribavir were taste disturbance, nausea, diarrhea, vomiting, and fatigue.
“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. “Today’s approval helps meet a significant unmet medical need by providing a treatment option for this patient population.”
Livtencity is supplied as 200mg tablets of maribavir in 28- and 56-count bottles, and will be available in the coming days.
- FDA approves first treatment for common type of post-transplant infection that is resistant to other drugs. News release. US Food and Drug Administration. November 23, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-common-type-post-transplant-infection-resistant-other-drugs.
- Takeda’s LivtencityTM (maribavir) approved by US FDA as the first and only treatment for people ages 12 and older with post-transplant cytomegalovirus (CMV), refractory (with or without genotypic resistance) to conventional antiviral therapies. News release. Takeda Pharmaceutical Company Limited. Accessed November 24, 2021. https://www.takeda.com/newsroom/newsreleases/2021/takeda-livtencity-maribavir-approved-by-us-fda/.
- Livtencity. Package insert. Takeda Pharmaceutical Company Limited; 2021. Accessed November 24, 2021. https://content.takeda.com/?contenttype=pi&product=liv&language=eng&country=usa&documentnumber=1.