Treatment of Advanced Waldenstrom's Macroglobulinemia - Clinical Trial

Introduction

Clinical and Translational Studies of a Phase II Trial of the Novel Oral Akt Inhibitor Perifosine in Relapsed or Relapsed/Refractory Waldenstrom's Macroglobulinemia.

Main Digest

Data Demonstrating a 35% Overall Response Rate with a Median Progression-Free Survival of 12.6 Months in Patients with Relapsed or Relapsed/Refractory Waldenstrom's Macroglobulinemia to be Published in the February 1, 2010 Issue of Clinical Cancer Research

Keryx Bio-pharmaceuticals, 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 immuno-histochemistry 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 immuno-histochemistry. 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 Bio-pharmaceuticals, 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.

Waldenstrom's Macroglobulinemia

Waldenstrom's Macroglobulinemia is a distinct Lymphoproliferative disorder characterized by bone marrow infiltration with lymphoplasmacytic cells, along with an IgM monoclonal gammopathy. Waldenstrom's affects an estimated 1,500 patients annually in the U.S. Despite advances in the therapy of Waldenstrom's, the disease remains incurable, thereby necessitating the development of novel therapeutics. There are no drugs currently FDA approved for Waldenstrom's, with nucleoside analogues, the proteasome inhibitor bortezomib (Velcade®), alkylating agents (chlorambucil) and rituximab (Rituxan®) often used to treat the disease.

KRX-0401 (Perifosine)

KRX-0401 (perifosine) is 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. The effects of perifosine on Akt are of particular interest because of the importance of this pathway in the development of most cancers, with evidence that it is often activated in tumors that are resistant to other forms of anticancer therapy, and the difficulty encountered thus far in the discovery of drugs that will inhibit this pathway without causing excessive toxicity. High levels of activated Akt (pAkt) are seen frequently in many types of cancer and have been correlated with poor prognosis.

Keryx has been granted a Special Protocol Assessment (SPA) from the FDA for the Phase 3 study of perifosine in multiple myeloma. Additionally, the FDA has granted perifosine Orphan Drug and Fast Track designations in multiple myeloma.

Keryx Bio-pharmaceuticals, Inc.

Keryx Bio-pharmaceuticals 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, and in Phase 2 clinical development for several other tumor types. Keryx is also developing Zerenex (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.

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