Keryx Biopharmaceuticals reaches agreement with FDA on SPA for Phase 3 trial of KRX-0401

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.