"Activation of the complement system during cardiopulmonary by-pass causes an acute, inflammatory reaction that can damage tissues, contributing to post-operative heart attacks and increased surgical complications that can impact patient survival," said Dr. Lazar. "This study showed that treatment with TP10, a potent inhibitor of complement activation, can limit this harmful inflammatory response, leading to improved post-surgical outcomes following cardiac surgery."
The multi-center, placebo-controlled, double-blind study enrolled 564 high-risk patients undergoing open heart surgery, who received a single intravenous dose of TP10 immediately prior to cardiopulmonary by-pass. Approximately 72% of those patients enrolled were male and approximately 28% were female. TP10 significantly inhibited complement activation in all treated patients compared to placebo for up to three days after surgery. Male patients receiving TP10 furthermore had a significant decrease from 32% to 20% (p=0.01) in the primary endpoint of the study, a composite of death, myocardial infarction (heart attack), prolonged (24 hours or more) intra-aortic balloon pump support, and prolonged (24 hours or more) intubation. Male patients receiving TP10 also showed a significant decrease in the combined endpoint of death or myocardial infarction from 27% to 17% (p=0.02).
The investigators did not see statistically significant clinical changes in the female patients participating in the study compared to placebo. Treatment with TP10 was well tolerated, and there were no differences in adverse events between those treated and those receiving placebo. The most commonly reported adverse events included anemia, platelet disorders and disturbances of cardiac function and rhythm, all of which are typically observed following cardiac surgery.
Alistair Wheeler, M.D., Vice President of Medical Affairs at AVANT Immunotherapeutics commented, "This study demonstrates that inhibiting complement activation can produce a real treatment benefit for men undergoing cardiopulmonary by-pass. It is unclear why this benefit was not seen in female patients in this trial, but it is well known that outcomes following cardiopulmonary bypass surgery are different in male and female patients. In addition, the numbers of women participating in this study were relatively small and thus less likely to show a clear statistical benefit."
"We are very encouraged by these results, which strongly support the advancement of TP10 into late-stage clinical development," said Una Ryan, Ph.D., AVANT President and Chief Executive Officer. "Our plans are to initiate a Phase IIb study in women around year end, to augment the safety data and further clarify the effect that TP10 has in that patient population, prior to advancing to a Phase III clinical study aimed at achieving product registration."
The Phase IIb study will be a double-blind placebo controlled trial of TP10 in 200-300 women undergoing cardiac surgery. AVANT plans to begin the double-blind, placebo-controlled study around year-end 2003 and conclude around year-end 2004. The study will be conducted at approximately 10 sites throughout the United States.
AVANT Immunotherapeutics, Inc. is engaged in the discovery, development and commercialization of products that harness the human immune system to prevent and treat disease. The company is developing a broad portfolio of vaccines addressing a wide range of applications including bacterial and viral diseases, chronic human disease, biodefense and food safety. These include single-dose, oral vaccines that protect against important disease-causing agents and a novel, proprietary vaccine candidate for cholesterol management. AVANT's goal is to demonstrate proof-of-concept for its products before leveraging their value through partnerships. Current collaborations encompass the development of an oral human rotavirus vaccine, vaccines to combat threats of biological warfare, and vaccines addressed to human food safety and animal health.
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This release includes forward-looking statements which reflect AVANT's current views with respect to future events and financial performance. These forward-looking statements are based on management's beliefs and assumptions and information currently available. The words "believe", "expect", "anticipate", "intend", "estimate", "project" and similar expressions which do not relate solely to historical matters identify forward-looking statements. Investors should be cautious in relying on forward-looking statements because they are subject to a variety of risks, uncertainties, and other factors that could cause actual results to differ materially from those expressed in any such forward-looking statements. These factors include, but are not limited to: (1) the integration of multiple technologies and programs; (2) the ability to adapt AVANT's vectoring systems to develop new, safe and effective orally administered vaccines against anthrax and plague or other bioterrorism threats or emerging health care threats; (3) the ability to successfully complete development and commercialization of TP10, CETi-1, CholeraGarde
Una S. Ryan, Ph.D.
President and CEO
AVANT Immunotherapeutics, Inc.
Alistair Wheeler, MD, MFPM
Vice President, Medical Affairs
AVANT Immunotherapeutics, Inc.