Maribavir safety and efficacy for cytomegalovirus infections among transplant recipients
1. This phase 2, parallel-group randomized control trial compared the safety and efficacy profile of maribavir versus valgancicvlovir among patients who received solid organ transplants, finding that both medications had comparable efficacy profiles in preventing CMV infection within 6 weeks of starting therapy.
2. Patients randomized to receive maribavir had a higher incidence of adverse events, with the most common adverse event noted to be dysgeusia and gastrointestinal-related symptoms.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Cytomegalovirus (CMV) infection is a potential concern among patients who have undergone solid organ transplantation. Current medications that are approved to prevent or treat CMV infection have toxic side effects such as myelosuppression, nephrotoxicity and electrolyte imbalances. Maribavir, a selective benzimidazole riboside, is a new medication that is being studied as a potential treatment for CMV infection prophylaxis. Maribavir prevents the exit of viral capsids from the cell nucleus by inhibiting CMV protein kinase UL97. In this phase 2 analysis, researchers compared the safety and efficacy profile of maribavir as compared to valganciclovir among patients who had received hematopoetic-cell or solid organ transplantation. Overall, researchers found that both regimens had similar efficacies in treating and preventing CMV infection. Patients randomized to receive maribavir had a higher incidence of gastrointestinal-related adverse events including dysgeusia. Patients randomized to receive valganciclovir had a higher incidence of neutropenia during the study period. Overall this study indicates that more research is warranted to evaluate maribavir and its treatment efficacy for this patient population.
Click to read the study in NEJM
In-depth [randomized clinical trial]: This trial was a phase 2, parallel-group randomized control trial conducted across 38 sites in six European countries between 2012 and 2014. Eligible patients who had screening CMV DNA levels between 1,000 to 100,000 copes per mm in their blood or plasma were randomized in a 1:1:1:1 ratio to receive either oral maribavir (dosed at 400mg, 800mg or 1200mg twice daily) or valganciclovir at a dose of 900mg twice daily for 3 weeks, followed by 900mg once daily. All treatment was given for up to 12 weeks. The primary safety endpoint of this study was the occurrence of adverse events among patients taking maribavir versus valganciclovir. The primary efficacy endpoint was the percentage of patients who had a response to treatment defined as undetectable CMV DNA in plasma within 3 or 6 weeks of treatment. There were 161 patients who underwent randomization, and 159 patients who received treatment and were included in the intention-to treat analysis (400mg maribavir n=40; 800mg maribavir n=40, 1200mg maribavir n=39; valganciclovir n=40). There were 72 of 117 patients randomized to receive maribavir who had a response to treatment within 3 weeks (62%; 95% CI: 52 to 70) compared to 22 of 39 patients in the valganciclovir group (56%, 95% CI: 40 to 72; RR 1.12; 95% CI: 0.84 to 1.49). At 6 weeks the response rate in the maribavir group increased to 79% (95% CI 70 to 86), and to 67% in the valganciclovir group (95% CI: 50 to 80; RR 1.20, 95% CI: 0.95 to 1.51). There was a higher incidence of adverse events reported among patients in the maribavir group (52/119=42%) compared to the valganciclovir group (13/40=32%). The most common adverse event reported in the maribavir group was dysgeusia. Gastrointestinal symptoms such as nausea, vomiting and diarrhea were also more common among the maribavir group. Neutropenia was notably less common in the maribavir group as compared to the valganciclovir group.
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