Keryx Biopharmaceuticals Announces Special Protocol Assessment Agreement with FDA for Phase 3 Trial of KRX-0401 (Perifosine) in the Treatment of Patients with Refractory Metastatic Colorectal Cancer

NEW YORK, Feb. 3 /PRNewswire-FirstCall/ -- Keryx Biopharmaceuticals, Inc. (Nasdaq: KERX) announced today that it has reached agreement with the U.S. Food and Drug Administration (FDA) regarding a Special Protocol Assessment (SPA) on the design of a Phase 3 trial for its PI3K/Akt pathway inhibitor, KRX-0401 (perifosine), in patients with refractory metastatic colorectal cancer. The SPA provides agreement that the Phase 3 study design adequately addresses objectives in support of a regulatory submission.

PHASE 3 TRIAL DESIGN:

The Phase 3 X-PECT (Xeloda® + Perifosine Evaluation in Colorectal cancer Treatment) trial will be 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 metastatic colorectal cancer. Patients must have failed available therapy including 5-fluorouracil (5-FU), oxaliplatin (Eloxatin®), irinotecan, bevacizumab (Avastin®) and, if K-Ras wild-type (WT), 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 (OS), with secondary endpoints including overall response rate (ORR: complete responses + partial responses), progression-free survival (PFS) and safety.  The median OS 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 OS, with an assumed median OS 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.  

Approximately 40 to 50 U.S. sites will participate in the study.  The study is expected to begin in 2Q 2010, and enrollment is expected to take approximately 12 months, with study completion expected in 2H 2011.  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.

Dr. Johanna Bendell, commented, "More active agents are needed to improve survival for patients with metastatic colorectal cancer.  We are very excited about this Phase 3 trial, which is based on the encouraging randomized Phase 2 data that demonstrated an improvement in overall survival and time to progression using perifosine plus capecitabine over placebo plus capecitabine in patients with metastatic colorectal cancer.  As such, we are moving forward with the randomized Phase 3 X-PECT trial, and we hope to continue to see these improvements in patient outcomes."    

Dr. Cathy Eng, added, "The updated Phase 2 data presented at the 2010 Gastrointestinal Cancers Symposium in Orlando, Florida, demonstrated promising activity and outcomes for heavily pretreated metastatic colorectal cancer patients treated with the combination of perifosine plus capecitabine and provided heightened awareness of the potential therapeutic role of an oral PI3K/Akt pathway inhibitor. The Phase 3 X-PECT trial will provide a greatly needed opportunity for our patients that would normally have very limited treatment options."

Ron Bentsur, Chief Executive Officer of Keryx, stated, "This SPA represents another important milestone for the company, and we wish to thank the FDA for their guidance and support in this process.  We also wish to thank the Phase 2 investigators and the experts that helped us obtain this SPA.  We are very encouraged by the colon Phase 2 data that was recently announced, which showed a statistically significant survival advantage in a refractory metastatic patient population."  Mr. Bentsur continued, "This is a very exciting time for Keryx, as we have transitioned into a late-stage development company with two drugs in Phase 3 pursuing three indications under SPAs.  We eagerly await the commencement of the X-PECT study within a few months."

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.

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 metastatic/advanced colorectal cancer. Currently, there are seven approved drugs for patients with metastatic colorectal cancer: 5-fluorouracil (5-FU), capecitabine (Xeloda(R)), irinotecan (Camptosar(R)), oxaliplatin (Eloxatin(R)), bevacizumab (Avastin(R)), cetuximab (Erbitux(R)), and panitumumab (Vectibix(R)). 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 the phosphoinositide 3-kinase (PI3K)/Akt pathway, a key signaling cascade that has been shown to induce cell growth and cell transformation. 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 also modulates a number of other key signal transduction pathways, including the JNK pathway, which are pathways associated with programmed cell death, cell growth, cell differentiation and cell survival. KRX-0401 is currently in a Phase 3 trial, under Special Protocol Assessment (SPA), in multiple myeloma, with a Phase 3 trial in refractory metastatic colorectal cancer, under SPA, pending commencement, and in Phase 2 clinical development for several other tumor types. 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, 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 study will not coincide with the data analyses from the Phase 2 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.