Anticancer Agent is Very Well Tolerated in Humans
����������� Amsterdam and Rockville, MD...EntreMed Inc. (NASDAQ: ENMD), today released data from three clinical trials on recombinant human Endostatin protein (rhEndostatin), an antiangiogenic agent that, in preclinical testing, has been shown to inhibit both the formation of new blood vessels and the growth of primary and metastatic tumors without toxicity.
����������� EntreMed announced data from its Phase I human clinical trial at Dana-Farber/Partners Cancer Care in Boston, Mass., and two National Cancer Institute (NCI) sponsored Phase I trials conducted at M.D. Anderson Cancer Center in Houston, Texas, and the University of Wisconsin Comprehensive Cancer Center in Madison, Wisconsin.
"EntreMed is very pleased with the success of this clinical study and with the clinical excellence of the investigators," said Dr. Edward Gubish, EntreMed's Executive Vice President of Research and Development, "We have data from over 60 patients with 20 different tumor types and over 4,000 individual administrations of rhEndostatin. What we have seen is very encouraging and we are actively planning the continuation of our clinical development of this agent."
����������� The data were presented at the "National Cancer Institute and European Organization for Research and Treatment of Cancer Annual Symposium on New Drugs in Cancer Therapy" in Amsterdam. The Dana-Farber principle investigators, Dr. Donald Kufe and Dr. Paul Eder, presented, "Recombinant Human Endostatin Demonstrates Safety, Linear Pharmacokinetics and Biological Effect on Tumor Growth Factors;" M.D. Anderson principle investigators, Dr. Roy Herbst and Dr. James Abbrussese, presented, "A Phase I Trial of Recombinant Human Endostatin in Patients With Solid Tumors: Pharmacokinetic, Safety, and Efficacy Analysis;" and Dr. James Thomas and Dr. George Wilding, University of Wisconsin, presented, "A Phase I Pharmacokinetic and Pharmacodynamic Study of Recombinant Human Endostatin."
����������� At the conference, researchers emphasized the primary purpose of all Phase I trials is to evaluate the safety and potential toxicity of an agent. The trials are not designed to measure how effective an agent is at treating disease.
����������� Still, researchers were enthused by promising results during the Phase I trials.
"The data were remarkable in that there were no safety concerns and blood levels were very predictable. Moreover, there were clinical responses seen even in this small trial in patients with advanced cancer," said Dr.Paul Eder of Dana Farber.
����������� Data presented today in Amsterdam includes the following observations:
rhEndostatin is well tolerated. There were no serious adverse events associated with rhEndostatin therapy.
����������� Partial response - tumor regressed over 50 percent. Using an MRI scan to measure the size of tumors, one patient with sarcoma in the jaw bone, after two months at 300 mg/m2 a day of rhEndostatin, experienced over 50 percent decrease in tumor measurements (MD Anderson).
����������� Minor Response. One patient with a neuroendocrine tumor had a minor response (decrease in tumor size of about 20 percent) and participated in the study for one year
(Dana Farber).
����������� Stable disease. Twelve patients received between four and twelve months of rhEndostatin therapy; of these, at least five patients had stable disease for a minimum of four months, with two of the patients receiving one year of therapy.
����������� Tumor blood flow and metabolism by PET scan. Decreases in tumor blood flow and glucose metabolism were seen in select patients. Generally, in states of disease including some types of cancer, a decrease in the use of glucose could possibly indicate a decrease in the activity level of the tumor cells (MD Anderson).
rhEndostatin is associated with measurable changes in blood flow. When measuring the amount of blood flowing through a tumor relative to the amount flowing through the heart, after 56 days of administering rhEndostatin, the flow through the heart was unchanged, but there was a decrease in the blood flow through the tumor in some patients (University of Wisconsin).
����������� Correlation between rhEndostatin and growth factor inhibition. There was a relationship between the dose of rhEndostatin administered and the presence of those serum markers (bFGF and VEGF in urine) that may be important biological indicators of new blood vessel growth. As the rhEndostatin dose increased, more patients demonstrated a decrease in their bFGF and VEGF urine levels (Dana Farber).
rhEndostatin did not interfere with normal skin angiogenesis. At doses administered, rhEndostatin did not affect the normal growth of blood vessels associated with wound healing (University of Wisconsin).
����������� "There was evidence of biological activity, patients who demonstrated stable disease, and tumor shrinkage recorded during these trials." Dr. Gubish said. "These data are preliminary and should not be taken out of context in these small trials, but the biological activity and the tumor responses we did see were an added bonus."
With an understanding of rhEndostatin's safety and pharmacokinetics (blood levels), EntreMed is continuing its rapid march to the marketplace with rhEndostatin. The next phase of clinical study is expected to begin early next year.
����������� EntreMed is currently developing several antiangiogenic drug candidates. EntreMed has already been involved with the development of one antiangiogenic drug (Thalomid (r)), which is currently on the market for leprosy. In addition, EntreMed has three cancer drugs in human trials (Endostatin, Angiostatin and 2-methoxyestradiol (2ME2)), four cancer therapy drugs in discovery or preclinical stages, and other agents in early development for oncology and non-oncology indications. Furthermore, through its internal discovery research program, EntreMed has a rich pipeline of new proteins, genes and small molecules being developed as next-generation antiangiogenic product candidates.