PRODUCT DESCRIPTION

SYNSORB CdŽ is SYNSORB's second product in Phase III clinical trials. Based on the same platform technology as SYNSORB Pk, SYNSORB CdŽ is designed to bind and remove the bacterial toxin that causes recurrent Clostridium difficile associated diarrhea (CDAD). CDAD is a common infection usually associated with antibiotic therapy, and is considered to be one of the most common nosocomial (hospital-acquired) infections. CDAD is prevalent in many institutional healthcare settings, especially nursing homes and extended care hospitals.

SYNSORB is conducting Phase III clinical trials on SYNSORB CdŽ at centres in the US, Canada and Mexico to determine its efficacy, when administered with a standard antibiotic course, in treating the recurrent form of CDAD.

DISEASE DESCRIPTION

Clostridium difficile (C. difficile) is the major causative agent of antibiotic associated bacterial diarrhea (CDAD) and pseudomembranous colitis. These conditions can be serious and result in severe diarrhea, cramping and abdominal pain and fever. C. difficile is a common component of human gut flora, but normally does not proliferate because it is held in check by the other flora of the adult colon. However, when normal intestinal micro flora becomes unbalanced, for example by antibiotic treatment, C. difficile is able to colonize the intestines in high numbers. Antibiotic therapy accounts for the majority of all cases of CDAD. However, any predisposing condition which alters normal intestinal flora, including any condition which requires extensive immunosuppressive treatment, can also lead to the development of CDAD.

C. difficile produces two exotoxins, an enterotoxin (Toxin A) and cytotoxin (Toxin B), which appear to play important roles in causing CDAD. It is Toxin A that is primarily responsible for the disease by binding to the protective epithelial cells in the intestine, resulting in the destruction of these cells and causing the secretion of fluid into the intestine. The destruction of these protective epithelial cells by the Toxin A represents the crucial step leading to the development of diarrhea. Once damage has occurred to the epithelial cells, the Toxin B can then gain access to underlying sensitive tissues and initiate additional clinical symptoms. The Toxin A receptor on epithelial cells has been shown to consist of one or more oligosaccharides, and because of this, the disease is a candidate for a SYNSORB - based therapy.

The current therapy for patients who suffer from CDAD is to remove the offending drug and begin oral administration of a different antibiotic, usually metronidazole. This form of therapy is effective in the majority of patients who suffer from CDAD. However, in approximately 20% of patients, the diarrhea returns after discontinuing antibiotic treatment. In such individuals, episodes continue to recur until the normal intestinal flora is reestablished and the number of C. difficile are reduced. This is a slow process as antibiotics which disturb the balance of the normal intestinal flora are administered each time the diarrhea occurs.