Keryx Biopharmaceuticals, Inc. Initiates Phase 3 Registration Trial of KRX-0401 (Perifosine) for Treatment of Patients with Refractory Advanced Colorectal Cancer

NEW YORK, April 8 /PRNewswire-FirstCall/ -- Keryx Biopharmaceuticals, Inc. (Nasdaq: KERX) announced today the initiation of a Phase 3 registration clinical trial for KRX-0401 (perifosine), the Company's novel, potentially first-in-class, oral anti-cancer agent that inhibits Akt activation in the phosphoinositide 3-kinase (PI3K) pathway, for the treatment of patients with refractory advanced colorectal cancer.

The Phase 3 trial, entitled the "X-PECT" (Xeloda® + Perifosine Evaluation in Colorectal cancer Treatment) trial, is a randomized (1:1), double-blind trial comparing the efficacy and safety of perifosine + capecitabine vs. placebo + capecitabine in approximately 430 patients with refractory advanced colorectal cancer. Patients must have failed available therapy including 5-fluorouracil (5-FU), oxaliplatin (Eloxatin®), irinotecan (Camptosar®), bevacizumab (Avastin®) and, if KRAS wild-type, failed therapy with prior cetuximab (Erbitux®) or panitumumab (Vectibix®).  For oxaliplatin-based therapy, failure of therapy will also include patients who discontinued due to toxicity. The primary endpoint for this study is overall survival, with secondary endpoints including overall response rate, progression-free survival and safety. This trial is being conducted pursuant to a Special Protocol Assessment (SPA) with the Food and Drug Administration.  Perifosine has also been granted Fast Track designation for the treatment of refractory advanced colorectal cancer.

Dr. Johanna Bendell, Director of GI Oncology Research for the Sarah Cannon Research Institute, Nashville, Tennessee, will lead the Phase 3 investigational team that includes Dr. Cathy Eng, Associate Medical Director for the Colorectal Center at MD Anderson Cancer Center in Houston, Texas.

Approximately 40 to 50 U.S. sites will participate in the study. Enrollment is expected to take approximately 12 to 14 months, with study completion expected in the second half of 2011.

Dr. Bendell stated, "We have now enrolled the first few patients on the Phase 3 X-PECT trial, which provides an important clinical trial option for patients with refractory advanced colorectal cancer.  The randomized Phase 2 data showed promising activity of perifosine plus capecitabine compared to placebo plus capecitabine.  I believe the X-PECT trial will soon provide us an answer as to the role of perifosine in the treatment of patients with refractory colorectal cancer."

Ron Bentsur, CEO of Keryx Biopharmaceuticals, commented:  "Keryx is committed to developing perifosine as a treatment that will provide meaningful therapeutic value for patients living with refractory advanced colorectal cancer.  The Phase 2 trial conducted in this setting provides strong rationale for the benefit of the perifosine/capecitabine combination in the treatment of advanced refractory colorectal cancer and we are extremely excited to initiate this Phase 3 registration trial, pursuant to our SPA, with the goal of potentially having the drug on the market for this indication by mid-2012.  We would like to thank Dr. Bendell, Dr. Eng and the team of colorectal investigators for the rapid initiation of this study and their invaluable guidance."

Perifosine is currently in a Phase 3 trial, under Special Protocol Assessment (SPA), for the treatment of relapsed/refractory multiple myeloma, with Orphan Drug Status and Fast Track Designation granted.

KRX-0401 (perifosine) is in-licensed by Keryx from Aeterna Zentaris Inc. in the United States, Canada and Mexico.

PHASE 3 TRIAL DESIGN:

The Phase 3 X-PECT (Xeloda® + Perifosine Evaluation in Colorectal cancer Treatment) trial is a randomized (1:1), double-blind trial comparing the efficacy and safety of perifosine + capecitabine (capecitabine is a chemotherapy marketed by Roche as Xeloda®) vs. placebo + capecitabine in approximately 430 patients with refractory advanced colorectal cancer. Patients must have failed available therapy including 5-fluorouracil (5-FU), oxaliplatin (Eloxatin®), irinotecan (Camptosar®), bevacizumab (Avastin®) and, if KRAS wild-type, failed therapy with prior cetuximab (Erbitux®) or panitumumab (Vectibix®).  For oxaliplatin-based therapy, failure of therapy will also include patients who discontinued due to toxicity. The primary endpoint is overall survival, with secondary endpoints including overall response rate (complete + partial responses), progression-free survival and safety. The median overall survival for the X-PECT study's targeted patient population, that has failed prior therapies as described above, is approximately 5 months. The X-PECT study will be powered at 90% to detect a statistically significant difference in overall survival, with an assumed median overall survival for the control arm of 5-6 months and 7-8 months for the perifosine arm. Approximately 360 events of death will trigger the un-blinding of the study.

About Colorectal Cancer

According to the American Cancer Society, colorectal cancer is the third most common form of cancer diagnosed in the United States. It is estimated that over 146,000 people were diagnosed with some form of colorectal cancer with over 49,000 patients dying from colorectal cancer in 2009. Surgery is often the main treatment for early stage colorectal cancer. When colorectal cancer metastasizes (spreads to other parts of the body such as the liver) chemotherapy is commonly used. Treatment of patients with recurrent or advanced colorectal cancer depends on the location of the disease. Chemotherapy regimens (i.e. FOLFOX or FOLFIRI either with or without bevacizumab) have been shown to increase survival rates in patients with advanced colorectal cancer. Currently, there are seven approved drugs for patients with advanced colorectal cancer: 5-fluorouracil (5-FU), capecitabine (Xeloda®), irinotecan (Camptosar®), oxaliplatin (Eloxatin®), bevacizumab (Avastin®), cetuximab (Erbitux®), and panitumumab (Vectibix®). Depending on the stage of the cancer, two or more of these types of treatment may be combined at the same time or used after one another. For example, FOLFOX combines 5-FU, leucovorin and oxaliplatin and FOLFIRI combines 5-FU, leucovorin and irinotecan. Bevacizumab, a VEGF monoclonal antibody, is commonly administered with chemotherapy. Typically, patients who fail 5-FU, oxaliplatin, irinotecan, and bevacizumab-containing therapies, and who have wild-type KRAS status receive EGFR monoclonal antibody therapy with either cetuximab or panitumumab. Once patients progress on these agents, there are no further standard treatment options.

About Special Protocol Assessments

The Special Protocol Assessment (SPA) process is a procedure by which the FDA provides official evaluation and written guidance on the design and size of proposed protocols that are intended to form the basis for a new drug application.

Final marketing approval depends on the results of efficacy, the adverse event profile and an evaluation of the benefit/risk of treatment demonstrated in the Phase 3 trial. The SPA agreement may only be changed through a written agreement between the sponsor and the FDA, or if the FDA becomes aware of a substantial scientific issue essential to product efficacy or safety. For more information on Special Protocol Assessment, please visit: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm080571.pdf

About Keryx Biopharmaceuticals, Inc.

Keryx Biopharmaceuticals is focused on the acquisition, development and commercialization of medically important pharmaceutical products for the treatment of life-threatening diseases, including 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 multiple myeloma and refractory advanced colorectal cancer, and in Phase 2 clinical development for several other tumor types.  Each of the KRX-0401 Phase 3 programs are being conducted under Special Protocol Assessment (SPA) agreements with the FDA.  Keryx is also developing Zerenex(TM) (ferric citrate), an oral, 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 pending commencement under an SPA agreement with the FDA. Keryx is headquartered in New York City.

Cautionary Statement

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; the risk that the data (both safety and efficacy) from the Phase 3 trials will not coincide with the data analyses from the Phase 1 and Phase 2 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 FDA website is not incorporated by reference into this press release and is included for reference purposes only.

SOURCE Keryx Biopharmaceuticals, Inc.