EXTON, Pa., June 27 /PRNewswire-FirstCall/ -- ViroPharma Incorporated today announced the presentation of new data from preclinical studies of non-toxigenic Clostridium difficile at the 5th International Meeting on the Molecular Biology and Pathogenesis of Clostridia (ClostPath), held from June 21st through 25th in Nottingham, UK. These data showed NTCD to be protective against the currently circulating hypervirulent “BI” strain of C. difficile in a hamster model. Additional data presented during the meeting support the protection data by demonstrating that NTCD displays higher adherence to human mucosal cells compared to the BI strain and to traditional strains of C. difficile.
“These data are important, as they demonstrate that non-toxigenic C. difficile protects in an animal model against the dangerous hypervirulent strain of C. difficile that appears to be responsible for an epidemic of C. difficile-associated disease (CDAD) that is spreading throughout the U.S., Canada, and Europe,” commented Colin Broom, M.D., ViroPharma’s chief scientific officer. “These data are not only significant, but essential as current and future therapies would need to consider effectiveness against this hypervirulent strain, which is associated with a substantial increase in the severity of CDAD in humans.”
“These new adherence data are particularly important since intestinal mucosal cell adhesion is a potential virulence factor of the BI strain,” added Dale Gerding, M.D., associate chief of staff for research at the Hines VA Hospital. “The superior adherence of NTCD strain M3 compared to the hypervirulent BI strains also further corroborates the finding that it is highly protective in an animal model for CDAD against the BI strains. The high level of protection afforded by NTCD against this virulent epidemic strain in preclinical models of CDAD is encouraging for the development of this new therapeutic approach.”
Protection data were described in an abstract entitled, “Non-Toxigenic Clostridium Difficile (CD) Protects Hamsters against Historic and Epidemic Toxigenic ‘BI’ Strains,” by K.J. Nagaro et al. In this study, the efficacy of NTCD in preventing disease in hamsters challenged with toxigenic BI strains was assessed. Animals were orally inoculated with one of two strains of NTCD (REA types M3 and T7) and then challenged with either a historic BI strain (BI1) or the BI strain causing the current epidemic (BI6), both of which have been previously shown to be 100% fatal in this model. Inoculation with M3 prevented fatal CDAD in 9 out of 10 hamsters challenged with BI6 (p<0.0003) and 10 of 10 challenged with BI1 (p<0.00005). Inoculation with T7 prevented fatal disease in 5 of 10 hamsters challenged with BI6 (p<0.02), and 10 of 10 challenged with BI1 (p<0.00005). The authors concluded that colonization with NTCD, particularly type M3, is highly effective in preventing CDAD in hamsters caused by REA group BI strains, and provides a novel approach with the potential to prevent CDAD caused by the new epidemic strains in humans.
The adherence data were described in an abstract entitled, “Hypervirulent Epidemic Strains Of Clostridium Difficile Have Altered Host Cell Adherence And Protein Expression,” by G. Vedantam et al. This study tested the hypothesis that increased adherence of the epidemic BI strain to mucosal lining contributes to the enhanced virulence of this strain. The results showed that an NTCD strain, REA type M3, displayed the highest adherence to Caco-2 human intestinal epithelial cells (a cell line that when grown in cell culture differentiates and assumes properties of intestinal mucosa cells), followed by BI strains including the circulating hypervirulent strains (BI6, BI8 and BI17). Toxigenic, non-epidemic strains showed the lowest adherence. Epidemic strains have enhanced adherence to human epithelial cells which is associated with an increased expression of surface layer proteins which may allow them to predominate in their environment and cause more severe disease outcomes that are not solely toxin-related. The high level of adherence demonstrated by the NTCD M3 strain corroborates the high levels of protection observed against BI strain challenge in the hamster model.
ViroPharma entered into a licensing agreement in February of 2006 with Dr. Gerding for the rights to develop non-toxigenic strains of C. difficile, including the M3 strain, for the treatment and prevention of CDAD. ViroPharma plans to initially focus its efforts on the opportunity to prevent recurrence of CDAD following treatment with Vancocin.
About Clostridium difficile
C. difficile is a bacterium, which under certain circumstances, typically after antibiotic therapy, can colonize the lower gastrointestinal tract where it may produce toxins which cause inflammation of the colon and diarrhea, and the associated complications of disease. Advanced age, gastrointestinal surgery/manipulation, long length of stay in healthcare settings, a serious underlying illness and compromised immunity are conditions associated with increased risk of disease. According to the CDC, there are approximately 3,000,000 cases of antibiotic-associated diarrhea per year, of which 15 to 25 percent are caused by C. difficile.
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/docs/pulvules_pi.pdf). ViroPharma currently focuses its drug development activities in viral diseases including cytomegalovirus (CMV) and hepatitis C (HCV). For more information on ViroPharma, visit the company’s website at http://www.viropharma.com.
Certain statements in this press release may contain forward-looking statements that involve a number of risks and uncertainties, including those relating to the non-toxigenic C. difficile program resulting in a therapy that is effective against the hypervirulent “BI” strain of C. difficile or that NTCD will continue to display encouraging activity by multiple measures in treatment of severe CDAD. Our actual results could differ materially from those results expressed in, or implied by, these forward-looking statements. The Company’s efforts in non-toxigenic C. difficile are preclinical stage programs, and as such are subject to risks and uncertainties. The advancement of promising product candidates through preclinical development and clinical development, and pursuing regulatory approval of product candidates that appear to demonstrate the requisite safety and efficacy, requires considerable time and expense. There can be no assurance that ViroPharma’s efforts in non- toxigenic C. difficile will yield positive results, will result in effective treatments in a timely manner, if at all, or that the FDA would approve any non-toxigenic C. difficile product candidates. The development and commercialization of pharmaceutical products is subject to risks and uncertainties. These factors, and other factors, including, but not limited to those described in ViroPharma’s annual report on Form 10-Q for the Quarter ended March 31, 2006 filed with the Securities and Exchange Commission 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.
ViroPharma Incorporated
CONTACT: William C. Roberts, Director, Corporate Communications,+1-610-321-6288; or Robert A. Doody, Manager, Corporate Communications,+1-610-321-6290, both of ViroPharma Incorporated
Web site: http://www.viropharma.com//
