The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for maribavir for the treatment of cytomegalovirus (CMV) infection in patients that are refractory with or without resistance (R/R), in solid organ transplant or hematopoietic stem cell transplant recipients.
Maribavir is an orally bioavailable anti-CMV compound that targets and inhibits the UL97 protein kinase and its natural substrates. The NDA submission is supported by 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 with R/R CMV infection who were recipients of hematopoietic stem cell or solid organ transplant.
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 apart.
Findings showed that 55.7% (n=131/235) of patients treated with maribavir achieved confirmed CMV viremia clearance compared with 23.9% (n=28/117) of those treated with conventional therapies (P <.001). Moreover, 18.7% of patients treated with maribavir maintained CMV viremia clearance and symptom control through week 16 vs 10.3% of those treated with conventional therapies (P =.013).
Additional subgroup analyses of the primary endpoint demonstrated that 55.6% of solid organ transplant recipients treated with maribavir achieved confirmed CMV viremia clearance compared with 26.1% of those on conventional therapies. Among hematopoietic stem cell transplant recipients, 55.9% of patients treated with maribavir achieved confirmed CMV viremia clearance vs 20.8% of those on conventional therapies.
As for safety, maribavir was associated with a lower incidence of treatment-related toxicities, including neutropenia (1.7% for maribavir vs 25% for valganciclovir/ganciclovir) and acute kidney injury (1.7% for maribavir vs 19.1% for foscarnet). Treatment-related adverse events leading to study discontinuation were 13.2% in the maribavir arm and 31.9% in the conventional antiviral therapy arm.
“If approved, maribavir has the potential to change the treatment landscape for post-transplant CMV, and the acceptance of this regulatory application is an important milestone on maribavir’s path forward,” said Obi Umeh, MD, Vice President and Maribavir Global Program Leader, Takeda.
- U.S. Food & Drug Administration grants Priority Review of maribavir for the treatment of post-transplant recipients with cytomegalovirus infection in those resistant and/or refractory to prior Anti-CMV treatment. [press release]. Osaka, Japan: Takeda Pharmaceutical Company Limited; May 21, 2021.
- Takeda’s maribavir phase 3 clinical trial met primary endpoint of superiority to conventional antiviral therapy in transplant recipients with refractory, with or without resistance, cytomegalovirus infection/disease. [press release]. Osaka, Japan: Takeda Pharmaceutical Company Limited; February 12, 2021.