NEW YORK, April 5, 2011 /PRNewswire/ -- Keryx Biopharmaceuticals, Inc. (NASDAQ: KERX) (the "Company") today announced that two posters on KRX-0401 (perifosine) were presented at the 102nd annual meeting of the American Association for Cancer Research currently ongoing at the Orange County Convention Center in Orlando, Florida. Perifosine, the Company's novel, potentially first-in-class, oral anti-cancer agent that inhibits Akt activation in the phosphoinositide 3-kinase (PI3K) pathway, is currently in Phase 3 clinical trials for refractory advanced colorectal cancer and multiple myeloma. Both of these Phase 3 programs are being conducted under Special Protocol Assessment (SPA) agreements with the FDA, and with Fast Track designations obtained for both indications. Perifosine is also in Phase 1 and 2 clinical development for several other tumor types.
Entitled, "Antitumor activity of novel Akt inhibitor, perifosine in gastric cell lines", Tae Soo Kim, Hyo Song Kim, Bo Ram Kwan, Chan Hee Park, Hei-Cheul Jeung, Woo Ick Jang, Juergen Engel, Hyun Cheol Chung, Jae Kyung Roh, Sun Young Rha, (Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea).
Perifosine showed single agent anti-proliferative activity in a variety of gastric cancer cell lines. In 8/13 cell lines resistant to 5-FU, perifosine showed a synergistic antiproliferative activity with 5-FU. In 72% of cell lines, high basal levels of pAkt were detected. Treatment with perifosine reduced tumor growth in nude mice inoculated subcutaneously with the YCC 2 gastric cancer cell line. Finally, an MTT based microarray analysis was performed to identify pharmacogenomic classifiers for synergy in 5-FU resistant cell lines.
Perifosine demonstrated antitumor activity in several gastric cancer cell lines. Furthermore, perifosine enhanced the antitumor activity of 5-FU including 5-FU resistant cell lines. 5-FU is the active metabolite of the pro-drug Xeloda(TM) (capecitabine), which is approved for the treatment of metastatic colorectal cancer and breast cancer in the U.S., as well as advanced gastric cancer in certain countries outside of the U.S.
Entitled "The Akt inhibitor Perifosine strongly enhances the antitumor and antivascular activity of CD34+ cells engineered to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)", A. Giacomini, S. L. Locatelli, M. Righi, L. Cleris, P.D. Longoni, M. Milanesi, M. Francolini, M. Magni, M. Di Nicola, A. M. Gianni, C. Carlo-Stella (Fondazione IRCCS Istituto Nazionale Tumori and University of Milan, Milan, Italy).
Pro-apoptotic TRAIL receptors present on tumor cells are known to represent a potential pharmaceutical target for cancer treatment. Perifosine stimulated the expression of pro-apoptotic TRAIL receptors on the multiple myeloma KMS-11 cell line, substantially reduced the levels of phosphorylated Akt and significantly enhanced the sensitivity of these cells for trail induced apoptosis. The same molecular effects were noted in the non-Hodgkin lymphoma cell line SU-DHL-4V. In this TRAIL resistant cell line, perifosine treatment substantially enhanced the cytotoxicity of TRAIL treatment to similar levels observed in the TRAIL sensitive multiple myeloma cell line.
The synergistic activity was confirmed in NOD/SCID mice xenograft models, where perifosine induced a down-modulation of Akt expression as well as TRAIL receptor upregulation in tumor cells and tumor endothelial cells.
Perifosine markedly enhanced the antitumor activity of the cellular TRAIL based treatment and was able to overcome TRAIL resistance both in vitro and in vivo. The results are in line with other studies demonstrating the synergistic effects of perifosine with cytotoxic drugs, including bortezomib and 5-FU
All abstracts can be viewed at www.aacr.org. A copy of the posters presented at AACR may be obtained by contacting the Company.
KRX-0401 (perifosine) is in-licensed by Keryx from AEterna Zentaris Inc. in the United States, Canada and Mexico.
ABOUT KERYX BIOPHARMACEUTICALS, INC.
Keryx Biopharmaceuticals is focused on the acquisition, development and commercialization of medically important pharmaceutical products for the treatment of cancer and renal disease. Keryx is developing KRX-0401 (perifosine), a novel, potentially first-in-class, oral anti-cancer agent that inhibits Akt activation in the phosphoinositide 3-kinase (PI3K) pathway, and also affects a number of other key signal transduction pathways, including the JNK pathway, all of which are pathways associated with programmed cell death, cell growth, cell differentiation and cell survival. KRX-0401 has demonstrated both safety and clinical efficacy in several tumor types, both as a single agent and in combination with novel therapies. KRX-0401 is currently in Phase 3 clinical development for both refractory advanced colorectal cancer and multiple myeloma, and in Phase 1 and 2 clinical development for several other tumor types. Each of the KRX-0401 Phase 3 studies is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA. Keryx is also developing Zerenex (ferric citrate), an oral, ferric iron-based compound that has the capacity to bind to phosphate and form non-absorbable complexes. The Phase 3 clinical program of Zerenex in the treatment for hyperphosphatemia (elevated phosphate levels) in patients with end-stage renal disease is being conducted pursuant to an SPA agreement with the FDA. Keryx is headquartered in New York City.
Some of the statements included in this press release, particularly those anticipating future clinical trials and business prospects for KRX-0401 (perifosine), may be forward-looking statements that involve a number of risks and uncertainties. For those statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Among the factors that could cause our actual results to differ materially are the following: our ability to successfully and cost-effectively complete clinical trials for KRX-0401 (perifosine); the risk that the data (both safety and efficacy) from ongoing clinical trials will not coincide with the data analyses from prior pre-clinical and clinical trials previously reported by the Company; and other risk factors identified from time to time in our reports filed with the Securities and Exchange Commission. Any forward-looking statements set forth in this press release speak only as of the date of this press release. We do not undertake to update any of these forward-looking statements to reflect events or circumstances that occur after the date hereof. This press release and prior releases are available at http://www.keryx.com. The information found on our website and the AACR website is not incorporated by reference into this press release and is included for reference purposes only.
Director - Investor Relations
Keryx Biopharmaceuticals, Inc.
E-mail: [email protected]
SOURCE Keryx Biopharmaceuticals, Inc.