Perifosine holds promise as a single agent for relapsed/refractory Waldenstrom's Macroglobulinemia

Jan 30 2010

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 the Journal of Clinical Cancer Research

Æterna Zentaris Inc. (Nasdaq: AEZS; TSX: AEZ) (the "Company"), a late-stage drug development company specialized in oncology and endocrinology, 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 perifosine (KRX-0401) for the treatment of advanced Waldenstrom's Macroglobulinemia ("Waldenstrom's"), will appear in the February 1, 2010 issue of the Journal 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 Multiple Myeloma. Like 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 FDA approved drugs for the treatment of Waldenstrom's. Keryx Biopharmaceuticals, Inc. (NASDAQ: KERX) is Æterna Zentaris' partner and licensee for perifosine in the United States, Canada and Mexico. Perifosine is also out-licensed to Handok in South Korea while Æterna Zentaris retains rights for the rest of the world.

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 37 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/b (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(R)) 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 or bortezomib."

Juergen Engel, President and CEO of Æterna Zentaris stated, "We are very pleased with these results as they provide additional evidence of perifosine's potential as a novel approach in treating multiple types of cancer, both as a single agent and in combination therapy. We now look forward to the future late-stage development of this compound in Waldenstrom's Macroglobulinemia, metastatic colon cancer as well as in multiple myeloma, for which perifosine is currently in an ongoing Phase 3 registration trial."