VP20621

According to published literature, approximately 20 to 30 percent of patients suffering from Clostridium difficile infection (CDI) will have at least one episode of relapse of disease. The goal of ViroPharma’s novel VP20621 (non-toxigenic C. difficile) program is to prevent such recurrence of disease.

Over the past several years, CDI has increased in severity and incidence. As such, the number of recurrent infections has also increased. According to a recent survey, 55 percent of participating US hospitals reported an increase in the number of treatment relapses over a recent 12 month period (Gelone et al. 2006). Because of this dramatic increase, finding new alternatives to prevent recurrent CDI remains an important medical goal.

Background
ViroPharma acquired VP20621 in February 2006 from Dale Gerding, of the Hines VA. The concept behind this novel treatment approach aims to prevent disease recurrence and involves the oral administration of non-toxin producing spores of C. difficile following initial treatment of acute CDI. The underlying concept is to first treat the disease with an effective product like Vancocin (PI) and eradicate the dangerous toxin-producing C. difficile which causes severe CDI. The treated patient could potentially then be dosed with oral VP20621 to re-colonize the GI tract and prevent the ‘bad’ bugs from re-infecting the colon until normal GI flora returns and the patient is no longer susceptible to disease

Status
ViroPharma has completed a Phase 1 clinical studies of VP20621, designed to determine the safety and tolerability of VP20621 dosed orally as single and repeat escalating doses in healthy young (18-45 years of age) and older (60 years of age and older) adults.  Antibiotic use is associated with disruption of gastrointestinal flora which renders individuals susceptible to C. difficile colonization. The goal of VP20621 dosing following antibiotic exposure is to colonize with this non-toxigenic strain of C. difficile and to prevent colonization by toxigenic strains, thereby preventing disease.

The Phase 1 study was designed to determine the safety and tolerability of VP20621 dosed orally as single and repeat escalating doses in healthy young (18 to 45 years of age) and older (60 years of age and older) adults. Because VP20621 was shown to be well tolerated following single and repeat doses in younger and older healthy subjects, the company also performed repeat dosing in older adults following exposure to oral antibiotic. The company has presented data from healthy subjects above 60 years of age who were pre-dosed with oral vancomycin to disrupt their gastrointestinal flora and render them potentially susceptible to C. difficile colonization. Subjects were subsequently given either placebo or VP20621 doses of 10⁴,10⁶, or 10⁸ spores (QD x 14 days). Conclusions from the study include:

• Multiple doses of VP20621 were generally well tolerated at all dose levels; there were no serious or severe adverse events, and no discontinuations from study drug due to adverse events.
• All 27 volunteers (100 percent) who were given VP20621 had positive non-toxigenic C. difficile stool cultures by day 6, suggesting that VP20621 rapidly colonizes the susceptible GI tract.
• No patient dosed with VP20621 tested positive for toxin-producing strains of C. difficile during the 28-day study period.
• By comparison, 5 of 9 subjects (56 percent) who received placebo (i.e. did not receive VP20621) tested positive for either toxin-negative or toxin-positive C. difficile during the study period.

The company intends to initiate Phase 2 clinical testing in the first half of 2011.