Early Results of Phase 2 Trial of Perifosine (KRX-0401) for the Treatment of Recurrent Malignant Gliomas Presented at the 12th Annual Scientific Meeting of Society for Neuro-Oncology
Poster presentation highlights response rate in subset of patients with Anaplastic Gliomas
NEW YORK, Nov. 19 /PRNewswire-FirstCall/ -- Keryx Biopharmaceuticals, Inc. (Nasdaq: KERX) today announced that early results of a phase II single agent trial of perifosine (KRX-0401) in patients with recurrent malignant gliomas was presented in a poster presentation on Saturday, November 17, 2007 at the 12th Annual Scientific Meeting of the Society for Neuro-Oncology, held in Dallas, Texas. The poster, entitled "A Phase II Trial of Perifosine for Recurrent/Progressive Malignant Gliomas, provided an update on the clinical activity of single agent perifosine in patients with malignant glioblastoma (GBM) and malignant anaplastic gliomas (AA).
Ph II Study - Interim Results
Twenty-five patients with advanced malignant gliomas were treated with a loading dose of 600 mg (150mg x 4) followed by 100 mg daily dose of perifosine. Patients must have failed prior radiation therapy and have shown unequivocal evidence for tumor progression by MRI or CT scan. There was no limitation on the number of prior relapses or prior therapies and patients with a KPS greater than or equal to 50 were eligible. Patients were not allowed to take enzyme-inducing anti-epileptic drugs (EIAED's). Response was measured by the MacDonald Criteria (PR greater than or equal to 50% decrease in bidirectional tumor area and SD = between 25% worse to 50% better). Patients were broken out into two groups with results as follows:
   Malignant Glioma  N    Evaluable   Partial   Stable     Overall (PR
                                         Response  Disease       + SD)
   All Patients     25       20        2 (10%)  4 (20%)       6 (30%)
   Glioblastoma     16       14          0      2 (14%)       2 (14%)
   Anaplastic
    Glioma           9        6       2* (33%)  2 (33%)       4 (66%)
    *1 Patient with Anaplastic Astrocytoma and 1 Patient with Anaplastic
                             Oligodendroglioma
The median Progression Free Survival (PFS) and Overall Survival (OS) in the Anaplastic Glioma group was 9 wks (range 2 - 50 wks) and 49 wks respectively. Toxicity was minimal with the following reported events (n): grade 1 nausea (1), grade 1 diarrhea (1), grade 2 pain (1) and grade 4 gout exacerbation (1). The study was designed to enroll at least 12 evaluable GBM patients and at least 10 evaluable AA patients. If at least 1 patient achieves 6 month PFS, the study would continue to enroll an additional subset of patients. Therefore, the GBM arm has been halted and the AA arm will continue to enroll. Final study updates will be reported at a future meeting.
I. Craig Henderson, MD, President of Keryx Biopharmaceuticals, commented "We want to further evaluate the role of perifosine in patients with malignant gliomas. The single agent activity observed in patients with anaplastic gliomas is of great interest as these patients are in need of additional therapies. We look forward to expanding this patient cohort."
For copies of the poster which was presented during the meeting, please contact Keryx Biopharmaceuticals.
Perifosine (KRX-0401) Mechanism of Action and Profile
Perifosine has been shown to inhibit or otherwise modify signaling through a number of different signal transduction pathways including Akt, MAPK, and JNK. Akt isoforms have been found to be overexpressed in renal, breast, prostate, and pancreatic cancers. Elevated levels of pAkt have been correlated with poor prognosis in patients with gastric, hepatocellular, endometrial, prostate, renal cell and head and neck cancers, as well as glioblastoma. The majority of tumors expressing high levels of pAkt were high-grade, advanced stage or had other features associated with poor prognosis.
The effects of perifosine on Akt are of particular interest because of 1) the importance of this pathway in the development of most cancers; 2) the evidence that it is often activated in tumors that are resistant to other forms of anticancer therapy; and 3) and the difficulty encountered thus far in the discovery of drugs that will inhibit this pathway without causing excessive toxicity.
To date, over 1,500 patients have been treated with perifosine in trials conducted both in the US and Europe. Its safety profile is distinctly different from that of most cytotoxic agents. It does not cause myelosuppression (depression of the immune system) or alopecia (hair loss) like many currently available treatments for cancer. In phase I/II trials it has induced tumor regressions and/or caused disease stabilization in a variety of tumor types. Responding patients, including stable disease, have been treated for months to almost 3 years, on both the daily and weekly schedule.
KRX-0401 (perifosine) is in-licensed by Keryx from Aeterna Zentaris, Inc. (Nasdaq: AEZS; TSX: AEZ) in the United States, Canada and Mexico.
About Malignant Gliomas
The American Cancer Society estimates that 20,500 malignant tumors of the brain or spinal cord (11,170 in men and 9,330 in women) will be diagnosed during 2007 in the United States. Approximately 12,740 people (7,150 men and 5,590 women) will die from these malignant tumors. This type of cancer accounts for approximately 1.3% of all cancers and 2.2% of all cancer-related deaths. Both adults and children are included in these statistics.
About Keryx Biopharmaceuticals, Inc.
Keryx Biopharmaceuticals, Inc. is focused on the acquisition, development and commercialization of medically important, novel pharmaceutical products for the treatment of life-threatening diseases, including diabetes and cancer. Keryx's lead compound under development is Sulonex(TM) (sulodexide oral gelcap), previously referred to as KRX-101, a first-in-class, oral heparinoid compound for the treatment of diabetic nephropathy, a life-threatening kidney disease caused by diabetes. Sulonex is in a pivotal Phase 3 and Phase 4 clinical program under a Special Protocol Assessment with the Food & Drug Administration. Additionally, Keryx is developing Zerenex(TM), an oral, iron- based compound that has the capacity to bind phosphate and form non-absorbable complexes. Zerenex is currently in Phase 2 clinical development for the treatment of hyperphosphatemia (elevated serum phosphorous levels) in patients with end-stage renal disease. Keryx is also developing clinical-stage oncology compounds, including KRX-0401, a novel, first-in-class, oral anti-cancer agent that modulates Akt, a protein in the body associated with tumor survival and growth, and a number of other key signal transduction pathways, including the JNK and MAPK pathways, which are pathways associated with programmed cell death, cell growth, cell differentiation and cell survival. KRX-0401 is currently in Phase 2 clinical development for multiple tumor types. Keryx also has an active in-licensing and acquisition program designed to identify and acquire additional drug candidates. Keryx is headquartered in New York City.
Cautionary Statement
Some of the statements included in this press release, particularly those anticipating future the financial performance and clinical and business prospects for KRX-0401, 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 complete the Phase 1 and Phase 2 clinical trials for KRX-0401; we may not be able to meet anticipated development timelines for KRX-0401 due to recruitment, clinical trial results, manufacturing capabilities or other factors; 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 intend 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 in our website is not incorporated by reference into this press release and is included as an inactive textual reference only.