Maribavir shows promise against CMV in transplant recipients
Twice-daily maribavir demonstrated similar efficacy as valganciclovir in clearing cytomegalovirus viremia in hematopoietic-cell or solid-organ transplant recipients, according to results from a phase 2 trial published today in The New England Journal of Medicine.
“Cytomegalovirus (CMV) infection commonly complicates hematopoietic cell and solid organ transplantation and is associated with increased morbidity and mortality,” Johan Maertens, MD, from the hematology department at the University Hospitals Leuven in Belgium, and colleagues wrote. “The available anti-CMV agents are effective but are limited by their toxic effects, including myelosuppression (ganciclovir and valganciclovir), nephrotoxicity (foscarnet and cidofovir), and electrolyte imbalances (foscarnet).”
According to the researchers, there is a need for effective anti-CMV agents with different mechanisms of action that offer more favorable safety profiles. They noted that maribavir — an orally bioavailable benzimidazole riboside — is active in vitro against CMV strains resistant to ganciclovir, foscarnet or cidofovir, and has a favorable safety profile, without associated nephrotoxicity or myelosuppression.
They conducted the phase 2, open-label trial of maribavir in recipients of hematopoietic-cell or solid-organ transplants who were aged 18 years or older with CMV reactivation between 1,000 to 100,000 DNA copies/mL. According to the study, they randomly assigned patients to maribavir at a dose of 400, 800 or 1,200 mg twice daily or the standard dose of valganciclovir for no more than 12 weeks.
A total of 159 patients received treatment, and postbaseline data were available for 117 patients in the maribavir group and 39 in the valganciclovir group. Among those who received maribavir, 62% (95% CI, 52%-70%) had a response to treatment within 3 weeks, compared with 56% (95% CI, 40%-72%) who had a response to valganciclovir, Maertens and colleagues reported. By 6 weeks, 79% (95% CI, 70%-86%) and 67% (95% CI, 50%-81%) of patients, respectively, had a response (risk ratio [RR] = 1.2; 95% CI, 0.95-1.51). The researchers noted that the percentages of patients with a response to treatment were similar among the maribavir dose groups. Two patients who had a response to treatment had a recurrence of CMV infection within 6 weeks after starting marivabir at a dose of 800 mg twice daily.
The maribavir group had a higher incidence of serious adverse events that occurred or worsened during treatment than the valganciclovir group, 44% vs. 32%, respectively, and more patients on maribavir discontinued the trial medication because of an adverse event (23% vs. 12%), according to Maertens and colleagues.
The researchers reported a higher incidence of gastrointestinal adverse events with maribavir and a higher incidence of neutropenia with valganciclovir.
“With its unique mechanism of action and evidence suggesting a lack of myelosuppression, maribavir should be studied further in patients who have undergone transplantation,” they wrote. – by Joe Gramigna
Disclosures: Maertens reports personal fees from Amgen, Astellas Pharma, Basilea, Cidara, F2G, Schering-Plough, Scynexis and Shire, as well as grants and personal fees from Bio-Rad, Gilead Sciences, Merck and Pfizer outside the submitted work. Please see the study for all other authors’ relevant financial disclosures.