Positive Phase 2 trial results of Keryx Biopharmaceuticals' KRX-0401 announced

Jan 29 2010

Keryx Biopharmaceuticals, Inc. (Nasdaq: KERX) (the "Company") today announced that an article entitled "Clinical and Translational Studies of a Phase II Trial of the Novel Oral Akt Inhibitor Perifosine in Relapsed or Relapsed/Refractory Waldenstrom's Macroglobulinemia," reporting Phase 2 data demonstrating the single agent activity of KRX-0401 (Perifosine) for the treatment of advanced Waldenstrom's Macroglobulinemia ("Waldenstrom's"), will appear in the February 1, 2010 issue of Clinical Cancer Research.  Perifosine, the Company's oral PI3K/Akt pathway inhibitor is currently being investigated in a Phase 3 trial, under Special Protocol Assessment, for the treatment of Advanced Multiple Myeloma.  Similar to Multiple Myeloma and Non-Hodgkin's Lymphoma, Waldenstrom's is a hematologic disease in which the cancer cells target the bone marrow.  There are currently no drugs FDA approved for the treatment of Waldenstrom's.  

Dr. Irene Ghobrial, Assistant Professor of Medicine, Bing Center for Waldenstrom's Macroglobulinemia at Dana-Farber Cancer Institute, led the Phase 2 study in which thirty-seven patients were treated with perifosine 150 mg daily for 6 cycles. In this study, 41% of the patients had 3 or more lines of prior therapy and 78% had 2 or more prior lines of therapy. Such prior therapies include nucleoside analogues, bortezomib, alkylating agents and rituximab, which are not approved for, but are often used in the treatment of Waldenstrom's.  The median % involvement of the bone marrow with lymphoplasmacytic cells was 70%, indicating advanced disease.  Stable or responding patients were allowed to continue therapy until progression. Of the 37 patients, 4 achieved a partial response (11%), 9 achieved a minimal response (24%), and 20 showed stable disease (54%). Overall, 89% (33/37) of patients treated with single agent perifosine were reported to have stable disease or better, while 11% (4 patients) demonstrated progression.  The median progression-free survival in the study was 12.6 months (90% C.I. (10.2, 22.7)), with a median overall survival of 26 months (90% C.I. (26 – upper limit not reached)). Perifosine was generally well-tolerated with gastrointestinal symptoms and fatigue reported as the most common adverse events related to therapy.

Also described in the article are translational studies using gene expression profiling and immunohistochemistry on pre- versus post-treatment patient samples conducted by Dr. Ghobrial.  Results showed that in the majority of samples tested, there was a significant reduction of phospho-GSK3/beta (downstream from Akt) using immunohistochemistry. Similarly, results demonstrated that perifosine significantly inhibited the expression of multiple members of the NF-kB family of genes, confirming previous in vitro studies showing activity of perifosine targeting this pathway.

"Perifosine as a single agent holds great promise in the treatment of patients with relapsed/refractory Waldenstrom's Macroglobulinemia," commented Dr. Ghobrial, who continued, "Responses were durable and occurred rapidly. The progression-free survival of 12.6 months is considered long compared to other targeted agents used in a similar population such as bortezomib (Velcade®), where the median time to progression was reported at 7.9 months.  We look forward to further evaluating perifosine's promise in this disease, either as a single agent or in combination with agents such as rituximab (Rituxan®) or bortezomib."

Ron Bentsur, Chief Executive Officer of Keryx Biopharmaceuticals, remarked "We are very excited to see this single agent activity of perifosine, which further demonstrates its potential as a targeted agent.  This Waldenstrom's data is of particular interest because, similar to multiple myeloma, Waldenstrom's is also a bone-marrow-based hematologic tumor.  Moreover, Waldenstrom's represents an unmet medical need for which there are no approved drugs and therefore could potentially provide us with an additional registration strategy for perifosine.  Finally, we wish to thank Dr. Ghobrial and her impressive team of investigators for their dedication to this Waldenstrom's program."

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. (Nasdaq: AEZS; TSX: AEZ) in the United States, Canada and Mexico.