SANG / RDP58 / Ulcerative Colitis
FREMONT, Calif.--(BW HealthWire)--May 21, 2002--SangStat (Nasdaq:SANG - News) announced today that RDP58 resolved spontaneous chronic colitis within 24 hours in primates (monkeys). The results of this study were released in an oral presentation at the Annual Digestive Disease Week (DDW) Meeting in San Francisco. Spontaneous chronic colitis in monkeys is believed to be similar to ulcerative colitis (UC) in humans. RDP58 is an orally active, potent anti-inflammatory peptide with multiple therapeutic activities, including inhibition of TNF-alpha, gamma interferon and IL-12.
"This study demonstrates that RDP58 effectively treats spontaneous colitis in non-human primates," said Roland Buelow, PhD, Senior Vice President of Discovery Research at SangStat. "We are particularly encouraged that the symptoms of colitis resolved so quickly and that the effect was long-lasting, in most animals for several months."
In the non-human primate study, 10 monkeys (rhesus or cynomologus) that had spontaneous chronic colitis for longer than four months and had failed treatment with existing antibiotic and steroid therapies were treated with oral RDP58. Doses of RDP58 ranged from 0.75 - 5mg/kg. Each monkey received a total of nine doses, and all doses were administered over a period of three weeks.
All animals given more than 2mg/kg of oral RDP58 (9 out of 10 animals) responded within one day. The only animal that did not respond immediately had received the lowest (0.75mg/kg) dose and had a minor response. Response was defined as a return to a normal stool. Responses lasted 6-41 weeks.
Phase I Study Shows RDP58 Safe in Humans
In a separate, Phase I human study, three groups (n=8 each) of healthy male volunteers received a daily dose of RDP58 (25mg, 100mg, or 300mg) for 28 days. Multiple safety laboratory tests were performed throughout the study. There were no differences in pre- and post-dosing test results. Side effects were mild and least common in the highest dosing group. There were no drug-related serious adverse events. These data show RDP58 to be safe and well tolerated in humans at doses up to 300mg daily for 28 days.
"The combination of efficacy data from the primate study and safety data in the Phase I study have provided SangStat with a solid foundation for the ongoing clinical development of RDP58 in Phase II studies of Crohn's disease and ulcerative colitis," said Raymond J. Tesi, MD FACS, Senior Vice President of Clinical Development and Medical Affairs at SangStat. "We hope to have the first indication of efficacy in patients with inflammatory bowel disease by the end of this year."
About RDP58
RDP58 (rationally designed peptide) is an anti-inflammatory peptide consisting of nine D-amino acids and glycine, developed by computer-aided rational design using artificial intelligence. RDP58 inhibits the synthesis of TNF-alpha, gamma interferon and IL-12 in various animal models. In addition, RDP58 inhibits heme oxygenase-1 (HO-1) in vitro, and causes up-regulation of HO-1 expression in vivo. Up-regulation of HO-1 has been associated with inhibition of inflammation. All of these activities may contribute to RDP58's therapeutic effects. RDP58 is currently being evaluated in Phase II clinical trials to treat mild-to-moderate inflammatory bowel disease (IBD -- both ulcerative colitis and Crohn's disease) in the United Kingdom and Europe.
TNF-alpha, gamma interferon and IL-12 are cytokines that that are often elevated in autoimmune disorders and are important in the activation of immune responses and inflammation. Animal models, including studies in primates, suggest that RDP58 can decrease levels of TNF and gamma interferon, reduce inflammation and improve clinical outcomes. RDP58 is orally active and different from injectable anti-TNF-alpha agents such as Enbrel® and Remicade® in that it inhibits the synthesis of TNF-alpha by preventing translation of TNF-alpha's mRNA, as opposed to neutralizing already circulating TNF. Also, because RDP58 does not appear to be absorbed into the bloodstream, SangStat believes that oral administration of RDP58 may reduce TNF-alpha and gamma interferon in the intestines with little or no effect elsewhere in the body. In contrast, subcutaneous or intravenous administration of anti-TNF-alpha, anti-gamma interferon, and anti-IL-12 agents appears to suppress these cytokines in a broad and unspecific way... |
