ViroPharma Incorporated has announced that its Phase 3 trial evaluating maribavir used as prophylaxis in allogeneic stem cell, or bone marrow, transplant (SCT) patients did not achieve its primary endpoint.
In the primary analysis, there was no statistically significant difference between maribavir and placebo in reducing the rate of CMV disease. In addition, the study failed to meet its key secondary endpoints. Maribavir was generally well tolerated in this clinical study.
"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.
Conference Call and Webcast
ViroPharma is hosting a live teleconference and webcast with senior management at 10:00 A.M. this morning to discuss the results of this Phase 3 study. To participate in the conference call, please dial 888-299-4099 (domestic) and 302-709-8337 (international). After placing the call, please tell the operator you wish to join the ViroPharma investor conference call.
Alternatively, the live webcast of the conference call can be accessed via ViroPharma's website at http://www.viropharma.com/. Windows Media or Real Player will be needed to access the webcast. An audio archive will be available at the same address until February 23, 2009.
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.
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