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Investigational Drug, RDP58, Shows Improved Remission Rate in Ulcerative Colitis Patients
FREMONT, Calif., April 9 /PRNewswire-FirstCall/ -- SangStat Medical Corporation announced today that preliminary results of its Phase II studies of RDP58 demonstrated a peak response rate of 77 percent and a 71 percent remission rate among patients with ulcerative colitis taking 200mg/day of active drug. Patients with ulcerative colitis who received 300mg/day of RDP58 achieved similar response and remission rates. Overall, both the response and remission rates were statistically significant. In Crohn's disease, although 66 percent of patients treated with 200mg/day of RDP58 achieved response, the study did not yield a statistically significant dose response. SangStat believes that additional analysis and clinical studies using higher dosing and longer administration may be needed to determine efficacy in Crohn's disease. RDP58 (rationally designed peptide) is the first in a new class of anti-inflammatory compounds being developed by SangStat.
"We are encouraged to see evidence of efficacy in our first proof-of-principle study," said Richard D. Murdock, Chairman, President and CEO at SangStat. "SangStat is excited that this first in a new class of anti-inflammatory compounds may represent an important advance in treating ulcerative colitis."
SangStat conducted two sets of clinical trials of RDP58: one in ulcerative colitis and one in Crohn's disease. The trials were similarly designed. All were randomized, blinded, placebo-controlled, multi-center Phase II studies in a total of 231 patients. RDP58 was provided as a powder to be mixed with water, and patients were instructed to drink the solution once each morning before meals. Patients received either placebo, 100mg/day, 200mg/day, or 300mg/day of RDP58 for 28 days. The primary endpoints were response and remission on day 28 of each study. Patients were followed for a total of 56 days.
"These results help us imagine the impact RDP58 may have on the lives of people with inflammatory bowel disease," said Raymond J. Tesi, MD, Senior Vice President, Clinical Development and Medical Affairs. "RDP58's effectiveness in ulcerative colitis is promising, but the results in Crohn's disease are less clear. As we have discussed previously, UC and Crohn's are different diseases, and we may need a higher dose or a longer dosing regimen in patients with Crohn's disease to see efficacy."
Evidence of Efficacy in Ulcerative Colitis (UC)
In the UC trials, response was defined as a decrease in the Simple Clinical Colitis Activity Index (SCCAI) score of 3 or more and remission was defined as a score of 3 or less. Patients entering the study had a SCCAI score of 4 - 9. A total of 127 patients were enrolled in the ulcerative colitis studies. The results were as follows:
Placebo 100mg 200mg 300mg Stat. Sig. Response 44% 33% 77% 72% p=0.0015 Remission 40% 29% 71% 72% p=0.0006 (n=43) (n=21) (n=31) (n=32) These results were statistically significant.
RDP58 was generally well tolerated. There was one severe adverse event attributed to RDP58, which was progression of disease in the 100mg/day study arm. No patient dropped out of the study due to adverse events. The most frequent side effects were mild or moderate and included nausea (range: 7% - 29% for RDP58, 5% for placebo) and headache (range: 19 - 33% for RDP58, 16% for placebo). These effects were not dose dependent and were not statistically significant.
Additional Investigation Needed in Crohn's Disease
Response in the Crohn's disease trials was defined as a decrease in the Crohn's Disease Activity Index (CDAI) score of 70 or more and remission was defined as a score of 150 or less. Patients entering the study had a CDAI score of 220 - 400. A total of 104 patients were enrolled in the Crohn's disease studies. Although 60 percent of patients who received 200mg/day of RDP58 achieved a response, the effect dropped back to 48 percent in the 300mg/day dosing arm. Specifically, the results were as follows:
Placebo 100mg 200mg 300mg Stat. Sig. Response 43% 44% 66% 48% p=0.450 Remission 20% 39% 48% 22% p=0.650 (n=30) (n=18) (n=29) (n=27)
Crohn's disease is a transmural disease, meaning it impacts the depth of the intestinal wall (unlike UC which is a mucosal disease, largely affecting only the epithelial layer of the colon) and may require increased or longer dosing to see significant improvement. SangStat believes that additional clinical studies into dosing and length of administration of RDP58 may be warranted to determine efficacy in Crohn's disease.
RDP58 was well tolerated. Among patients with Crohn's disease, all serious adverse events related to RDP58 were disease progression except for one case of leukopenia in the 300mg/day arm that was deemed possibly related to RDP58. However, this patient was also on azathioprine during the study. The most frequent side effects were mild or moderate and included nausea (range: 10% - 50% for RDP58, 13% for placebo) and headache (range: 7% - 39% for RDP58, 33% for placebo). These were not dose dependent and only headache was statistically significant (p=0.0068). (Headache was most prominent in the placebo and 100mg/day arm.) No patients required dose modification and no patients dropped out of the study due to an RDP58 related adverse event.
SangStat to host Research & Development Day
SangStat will host a Research and Development Day (R&D Day) on Tuesday, April 15, 2003 in New York to discuss the results of the Phase II studies, as well as provide an update on the mechanism of action of RDP58 and discuss data from RDP58 in new indications. The lead investigator for the RDP58 Phase II studies will be present to interact with the investment community. The logistical information follows:
SangStat R&D Day The Pierre Hotel 5th Avenue at 61st Street New York City 8:00 a.m. - Breakfast 9:00 a.m. - Symposia 12:00 p.m. - Lunch Speakers will include: Simon Travis, MD, Principal Investigator Professor of Medicine John Radcliffe Hospital Oxford University Raymond J. Tesi, MD, FACS Senior Vice President, Clinical Development and Medical Affairs SangStat Timothy Fong, PhD Vice President, Discovery Research SangStat Richard D. Murdock Chairman, President and CEO SangStat Agenda to follow.
Please RSVP to Dana King, Trout Group, 212-477-9007, ext. 24 or Bill Martin, SangStat, 510-789-4331.
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 blocks the p38 and JNK map kinase pathways and inhibits the synthesis of TNF-alpha, gamma interferon and IL-12 in various animal models. In addition, RDP58 causes up-regulation of heme oxygenase (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.
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. 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, 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.
Inflammatory Bowel Disease
Crohn's disease and ulcerative colitis are diseases that are grouped together as inflammatory bowel disease (IBD). The Crohn's and Colitis Foundation of America estimates that there may be up to 1,000,000 Americans with either ulcerative colitis or Crohn's disease, roughly half of that number for each disease. SangStat is developing RDP58 for treatment of these and other inflammatory diseases.
SangStat is a global biotechnology company focused on immunology and working to discover, develop and market high value therapeutic products in the autoimmune, hematology/oncology and immunosuppression areas. SangStat's U.S. headquarters are in Fremont, California. SangStat also maintains a strong European presence, including direct sales and marketing forces in France, Germany, Italy, Spain, and the UK, and distributors throughout the rest of the world. SangStat's stock is traded on the Nasdaq under the symbol "SANG." The company's web site is located at http://www.sangstat.com/.
This press release contains "forward-looking" statements. These forward-looking statements include statements on future developments relating to the RDP clinical trials and regulatory reviews, potential clinical utility of RDP, tolerance, side effects, and efficacy generally, and the possible efficacy in Crohn's disease in particular, plans with respect to further research and development, and whether new compounds could emerge from the RDP pipeline. There are a number of important factors that could cause results to differ materially from those indicated by these forward-looking statements, including further qualification as our understanding of these results develops as a result of future events and otherwise. Factors that could cause actual results to differ materially include, without limitation, problems in the RDP and other studies; issues resulting from additional data or analysis of data from the RDP trials; complications or delays in conducting toxicology or clinical trials; problems with regulatory reviews; patent or other litigation; licensing or product transactions. For a discussion of these and other factors that might result in different outcomes, see "Risk Factors" in SangStat's 2002 Annual Report on Form 10-K, its 2002 quarterly reports on Form 10-Q and other documents filed with the Securities and Exchange Commission. SangStat assumes no obligation to update any such forward-looking statements, risks or reasons why actual results might differ.