ViroPharma Completes Study Of Maribavir In Stem Cell Transplant Patients
ViroPharma Incorporated completed enrollment in its pivotal Phase 3 study of maribavir in stem cell transplant patients. This international Phase 3 study is evaluating the efficacy, safety and tolerability of prophylactic use of maribavir administered orally for up to 12 weeks for the prevention of cytomegalovirus (CMV) disease in recipients of allogeneic stem cell transplants (SCT). The study also will evaluate the pharmacokinetics of maribavir in this subject population. It is being conducted in 90 transplant centers in the U.S., Canada, and Europe.
"Maribavir may mark the first new advancement in CMV therapeutics for transplant recipients in many years," stated Stephen Villano, M.D., vice president, clinical research and development at ViroPharma. "CMV can cause significant and potentially deadly clinical manifestations among transplant recipients, and maribavir represents the opportunity for a shift in CMV treatment paradigm toward prophylaxis against CMV, thus preventing CMV viral infection and disease and allowing for enhanced focus on other aspects of patient outcome following transplantation."
The company also provided the timing of future milestones in the development of maribavir in SCT. These include:
-- Data collection for the 6-month assessments will continue through the end of November 2008;
-- Top line Phase 3 clinical data is expected to be announced in the first quarter of 2009;
-- Filing of the initial NDA (New Drug Application) in the U.S., MAA (Marketing Authorization Application) in Europe, and NDS (New Drug Submission) in Canada for maribavir in SCT patients based on the 6-month assessments is expected in the third quarter of 2009;
-- The company will announce the timelines for the ongoing Phase 3 study in liver transplant at a later date, including completion of enrollment and top line data. The company intends to file its supplemental NDA, NDS and MAA variation for this additional opportunity as soon as possible following receipt of initial marketing approvals in SCT.
"These are significant milestones for the development of this important drug, and we are excited by the global interest and support for maribavir among transplant physicians throughout the U.S., Europe and Canada," commented Vincent Milano, ViroPharma's president and chief executive officer.
CMV is among the most important infectious causes of significant morbidity and mortality in transplant patients. Approximately 60 percent of all at-risk allogeneic stem cell (bone marrow) transplant patients will show evidence of CMV infection in the first 100 days post transplant and despite treatment with currently available therapies approximately 10 percent of these patients will progress to develop CMV disease, which may manifest as deadly complications such as pneumonia or gastrointestinal disease. CMV infection is also associated with indirect effects in transplant recipients, including adverse immunologic effects (graft versus host disease (GvHD) after bone marrow transplantation and graft rejection after solid organ transplantation), serious bacterial and fungal infections, and reduced overall survival rates.
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 have been randomized to receive maribavir or matching placebo in a 2:1 randomization ratio. All patients will receive maribavir 100 mg BID or placebo for a maximum duration of 12 weeks, and will then be followed for an additional 12 weeks to reach the 6-month post-transplant analyses for regulatory filing purposes. All patients will then be followed for an additional 24 weeks.
Enrolled subjects will undergo testing for CMV infection at least weekly. CMV surveillance includes 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 is detected during the study drug administration period (or if CMV organ disease is diagnosed), study drug will be discontinued and the subject will be managed according to standard CMV treatment practices at the transplant center.
The primary efficacy endpoint will be the incidence of CMV disease within six months post-transplant, which is predicted to be approximately nine percent in the placebo (current standard of care) arm based on data from the Phase 2 study, data from published literature, and information from transplant center databases. Following extensive dialogue with FDA, a number of key secondary endpoints associated with CMV infection have been identified and assessment of these endpoints will be 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.