Expression Genetics, Inc., has announced the completion of a Phase I clinical study evaluating the Company's lead drug candidate, EGEN-001.
The study, conducted at The University of Alabama at Birmingham and Baylor College of Medicine, evaluated the safety, tolerance, preliminary efficacy, and biological activity of the EGEN-001 in 13 patients with advanced recurrent epithelial ovarian cancer. The product, utilizing the Company's proprietary TheraPlas(R) delivery technology, is composed of interleukin-12 (IL-12) gene expression plasmid formulated with a biocompatible delivery polymer and is designed to increase local concentration of IL-12 protein. IL-12 is a potent anti-cancer cytokine which works by enhancing the body's immune system against cancer and inhibiting tumor blood supply. EGEN-001 for treatment of ovarian cancer has been granted Orphan Drug Status by the FDA.
The Phase I clinical trial was an open-label dose escalation study involving four dose levels of EGEN-001 administered intraperitoneally by four weekly infusions in chemotherapy-resistant advanced stage recurrent ovarian cancer patients. The treatment was well tolerated with no apparent dose- related trends in clinical laboratory, ECG, or vital sign parameters. General observations included abdominal cramping, mild to moderate peritonitis, nausea, and mild elevation of body temperature. These data demonstrate that this IL-12 gene therapeutic is safe for intraperitoneal administration in ovarian cancer patients.
Several clinical and biological parameters were evaluated as secondary endpoints of this study. Tumor burden of patients was monitored during treatment and results show 31% of patients showed stable disease. To date, the overall median survival is over 12.2 months with 7 out of 13 patients still surviving. There appeared to be some trend with respect to clinical benefit in the patients treated with higher dosages. IL-12 plasmid was detectable in peritoneal fluid of all evaluable patients and in blood samples of only a few patients at considerably lower level, suggesting that the plasmid delivery following EGEN-001 administration was localized at the delivery site, a major advantage of EGEN-001 therapy over recombinant protein therapy. The IP administered EGEN-001 was biologically active since it increased the peritoneal levels of interferon-gamma, the predominant cytokine activated by IL-12, in all patients.
"We are quite pleased with the safety profile of EGEN-001 observed in this initial clinical trial and are encouraged by some of the preliminary efficacy and activity results we have seen resulting from the administration of EGEN- 001 monotherapy in advanced ovarian cancer patients," said Dr. Danny H. Lewis, CEO of Expression Genetics. "We have completed the necessary regulatory process and expect to immediately begin enrollment of patients in our next study which will combine EGEN-001 administration with conventional chemotherapy in platinum-sensitive recurrent ovarian cancer patients."
The lead investigator, Ronald Alvarez, M. D., Director of Gynecologic Oncology, The University of Alabama at Birmingham, stated, "We are encouraged by the initial clinical results of this trial and look forward to moving ahead with expanded clinical testing of EGEN-001 in order to evaluate the safety of this experimental drug in combination with paclitaxel and platinum based chemotherapy treatment regimens."
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