EXTON, Pa., June 2 /PRNewswire-FirstCall/ -- ViroPharma Incorporated today announced the publication of results of its previously described Phase 2 study showing that maribavir, when used as prophylaxis, reduced the rate of cytomegalovirus (CMV) reactivation and was well tolerated when compared to placebo in allogeneic stem cell, or bone marrow, transplant patients. These results were published in the June 1 issue of Blood, the official journal of the American Society of Hematology (ASH) and previously presented in 2006 at the annual ASH meeting in Orlando, Fl.
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.
In a 111 subject study, maribavir significantly reduced the rate of CMV infection requiring treatment across all dose ranges (15 percent, p=0.001; 30 percent, p=0.051 and 15 percent, p=0.002 in 100 mg BID, 400 mg QD, 400 mg BID doses respectively), compared to placebo (57 percent). No patients taking maribavir at any dose developed CMV disease, compared to the placebo group in which three subjects (11 percent) developed the disease. Moreover, there were no reports of late CMV disease across any treatment groups with a maximum follow up period of five months post-transplant.
“These results are important because they suggest that maribavir has the potential to shift the CMV management strategy in stem cell transplant from pre-emptive therapy to prophylaxis,” said Drew J. Winston, M.D., University of California, Los Angeles Medical Center. “It is clear that maribavir has the potential to offer an important new and safer option for clinicians to prevent CMV disease in transplant patients.”
Among other observations, GvHD of grade 2 or higher, a common complication in bone marrow transplants, also was found to be less common in the three maribavir treatment arms (14 percent; 29 percent; 23 percent) than in the placebo group (46 percent).
“While this dose-ranging study evaluated the safety and the ability of maribavir to prevent viral reactivation in bone marrow transplant patients, we are particularly encouraged by the possibility that maribavir may help reduce the rate of CMV disease and associated morbidity, something we are investigating in our current Phase 3 study,” said Stephen Villano, M.D., vice president, clinical research and development at ViroPharma.
The most common adverse events in the maribavir treatment groups were taste disturbance, nausea and vomiting. Maribavir did not cause renal toxicities or myelosuppression.
ViroPharma is currently conducting two pivotal Phase 3 studies with maribavir, one in allogeneic stem cell transplant recipients and the other in liver transplant recipients. The company expects to file its initial NDA and MAA for maribavir in SCT patients in the third quarter of 2009.
Study Design
The maribavir Phase 2 clinical trial was a randomized, double blind, placebo-controlled, dose-ranging study conducted at 13 transplant centers across the U.S. involving CMV-seropositive subjects who had undergone allogeneic stem cell transplantation. A total of 111 subjects were randomized 3:1 to receive placebo or maribavir in each of three ascending dose groups (100 mg BID, 400 mg QD, 400 mg BID). All subjects were monitored frequently for CMV infection, and if CMV infection was detected, study drug (maribavir or placebo) was discontinued and the subject was managed according to current standards of care at each transplant center, including starting pre-emptive anti-CMV treatment at the discretion of the investigator.
The objectives of this study included an evaluation of the safety and tolerability of maribavir administered orally for up to 12 weeks, and an evaluation of the prophylactic activity of maribavir in preventing CMV reactivation in CMV seropositive recipients of allogeneic stem cell transplants.
About maribavir
Maribavir is a potent and 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.
About Cytomegalovirus
CMV is a member of the herpes virus group, which includes the viruses that cause chicken pox, mononucleosis, herpes labialis (cold sores), and herpes genitalis (genital herpes). Like other herpesviruses, CMV has the ability to remain dormant in the body for long periods of time. Human CMV infection rates average between 50 percent and 85 percent of adults in the U.S. by 40 years of age, but in healthy adults causes little to no apparent illness. However, in immunocompromised individuals including cancer patients, HIV patients, and transplant patients, and in children born with primary CMV infection, CMV can lead to serious disease or death. Patients who are immunosuppressed following hematopoietic stem cell (bone marrow) or solid organ transplantation are at high risk of CMV infection. In these patients, CMV disease can lead to severe conditions such as pneumonitis or hepatitis, or to complications such as acute or chronic rejection of a transplanted organ. While currently available systemic anti-CMV agents are effective against the virus, their use is limited by toxicities, most notably bone marrow suppression and renal impairment.
About ViroPharma Incorporated
ViroPharma Incorporated is a biopharmaceutical company dedicated to the development and commercialization of products that address serious diseases treated by physician specialists and in hospital settings. ViroPharma commercializes Vancocin(R), approved for oral administration for treatment of antibiotic-associated pseudomembranous colitis caused by Clostridium difficile and enterocolitis caused by Staphylococcus aureus, including methicillin- resistant strains (for prescribing information, please download the package insert at http://www.viropharma.com/Products.aspx). ViroPharma currently focuses its drug development activities in infectious diseases including cytomegalovirus (CMV) and C. difficile. For more information on ViroPharma, visit the company’s website at http://www.viropharma.com.
Certain statements in this press release contain forward-looking statements that involve a number of risks and uncertainties. Forward-looking statements provide the Company’s current expectations or forecasts of future events. Forward looking statements in this press release include statements regarding ViroPharma’s clinical development programs, including statements that maribavir represents the opportunity for a shift in CMV treatment paradigm toward prophylaxis against CMV and our ability to file our initial NDA and MAA for maribavir in stem cell transplant patients in the third quarter of 2009. Our actual results could differ materially from those results expressed in, or implied by, these forward-looking statements. The development and commercialization of pharmaceutical products is subject to risks and uncertainties. The antiviral and tolerability data that were elucidated in our Phase 2 study designed to assess the rate of CMV reactivation in patients undergoing allogeneic stem cell transplantation may not be predictive of the results of our Phase 3 programs in allogeneic stem cell transplantation or liver transplant patients and further testing such as the ongoing Phase 3 clinical studies may not support any or all of the statements in this press release. There can be no assurance that that our Phase 3 programs will yield positive results, that our plan to file an NDA, MAA or other marketing petition for maribavir based upon the phase 2 and phase 3 stem cell clinical trial results, but prior to the completion of the phase 3 solid organ clinical trial will be successful as the regulatory agencies may view the data as insufficient or inconclusive, request additional data, delay any decision past the time frames anticipated by us, limit the approved indications, or deny the approval of maribavir. These factors, and other factors, including, but not limited to those described in ViroPharma’s annual report on Form 10-K and quarterly reports on Form 10-Q filed with the Securities and Exchange Commission during 2008, could cause future results to differ materially from the expectations expressed in this press release. The forward-looking statements contained in this press release may become outdated over time. ViroPharma does not assume any responsibility for updating any forward-looking statements.
CONTACT: Kristina Broadbelt, Assistant Director, PR & Advocacy,
+1-610-321-2358, or Robert A. Doody, Manager, Corporate Communications,
+1-610-321-6290, both of ViroPharma Incorporated
Web site: http://www.viropharma.com//
