You are here
Maribavir Fails to Meet Study Goals
"We are extremely disappointed by the outcome of this pivotal study," said Vincent J. Milano, ViroPharma's president and chief executive officer. "We just received these data and there are far more questions than answers; we still have a significant amount of work to do to fully understand this outcome and its impact on the overall program. Our disappointment is no doubt shared by physicians and transplant patients, who must today contend with CMV disease."
The primary endpoint of this Phase 3 study was the incidence of CMV disease, confirmed by an independent endpoint committee, within 6 months post-transplant. The incidence of CMV disease within 6 months was 4.4 percent for maribavir compared to 4.8 percent for placebo (P=0.79). The first of four key secondary endpoints was the rate of initiation of anti-CMV treatment within 6 months, which was 37.9 percent for maribavir compared to 40.5 percent for placebo (P=0.49). In addition, the incidence of graft-versus-host disease, mortality and CMV disease-free survival was comparable between the groups.
SCT Phase 3 Study Design
This study is a randomized, double-blind, placebo-controlled, multicenter pivotal Phase 3 study in 681 patients who have undergone allogeneic stem cell transplantation. Following transplantation and transplant engraftment, eligible patients were randomized to receive maribavir or matching placebo in a 2:1 randomization ratio. All patients received maribavir 100 mg BID or placebo for a maximum duration of 12 weeks, and followed for an additional 12 weeks to reach the 6-month post-transplant analyses for regulatory filing purposes. All patients were then followed for an additional 24 weeks.
Enrolled subjects underwent testing for CMV infection at least weekly. CMV surveillance included weekly testing at a central laboratory for the presence of CMV pp65 antigenemia and for the presence of CMV DNA in plasma using a polymerase chain reaction (PCR). If CMV infection was detected during the study drug administration period (or if CMV organ disease was diagnosed), study drug was discontinued and the subject was managed according to standard CMV treatment practices at the transplant center.
The primary efficacy endpoint was the incidence of CMV disease within six months post-transplant. Following extensive dialogue with FDA, a number of key secondary endpoints associated with CMV infection were identified and assessment of these endpoints was essential in assessing the clinical benefit of maribavir. These key secondary endpoints include incidence of initiation of preemptive anti-CMV therapy, incidence of graft-versus-host disease, mortality and CMV disease-free survival.
Maribavir is a selective, orally bioavailable Phase 3 antiviral drug with a unique mechanism of action against cytomegalovirus and a favorable clinical safety profile to date, including no evidence of renal toxicities or myelosuppression (a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets). Maribavir is a member of a new class of drugs called benzimidazole ribosides. Unlike currently available anti-CMV agents that inhibit CMV DNA polymerase, maribavir inhibits viral DNA assembly and egress of viral capsids from the nucleus of infected cells. Maribavir also has demonstrated activity in vitro against strains of CMV that are resistant to current anti-CMV therapies.