Perifosine observed to be an effective novel agent in neuroblastoma cells in vitro and in vivo
Phase 1 data of single agent perifosine as a treatment for recurrent solid tumors in pediatric patients, including neuroblastoma patients, to be presented at ASCO
QUEBEC CITY, May 17 /CNW Telbec/ - Aeterna Zentaris Inc. (NASDAQ: AEZS, TSX: AEZ) (the "Company"), a late-stage drug development company specialized in oncology and endocrine therapy, today announced publication of an article in the May 12th Journal of the National Cancer Institute, entitled "In Vitro and In Vivo Inhibition of Neuroblastoma Tumor Cell Growth by AKT Inhibitor Perifosine," demonstrating the single agent activity of perifosine (KRX-0401) in neuroblastoma tumor preclinical models. Neuroblastoma is the most common pediatric solid tumor. Perifosine, the Company's novel, potentially first-in-class, oral anti-cancer agent that inhibits Akt activation in the phosphoinositide 3-kinase (PI3K) pathway, is currently being investigated in a Phase 1 study as a single agent treatment for recurrent solid tumors, including neuroblastoma, in pediatric patients. Perifosine is licensed to Keryx Biopharmaceuticals (Keryx) (Nasdaq: KERX), in the United States, Canada and Mexico. Aeterna Zentaris has also out-licensed perifosine to Handok in South Korea, while retaining rights for the rest of the world. Perifosine is also currently in Phase 3 trials in multiple myeloma and colorectal cancer, as well as in Phase 2 trials for multiple types of cancer.
The article states that activated Akt is a marker of decreased event-free or overall survival in neuroblastoma patients, and that the aim of this study was to investigate the effect of perifosine, an Akt inhibitor, as a single agent on neuroblastoma cell growth in vitro and in vivo. The preclinical study investigated the activity of perifosine on four human neuroblastoma cell lines, as well as on the survival, tumor growth, and activation status of Akt in mice bearing human neuroblastoma xenograft tumors. Perifosine showed a statistically significant reduction in neuroblastoma cell survival, slowed or regressed tumor growth, and increased survival in mice bearing neuroblastoma tumors. A decreased level of activated Akt was also observed in perifosine-treated neuroblastoma cells and xenograft tumors.
The investigators concluded that perifosine inhibited the activation of Akt and was an effective cytotoxic agent in neuroblastoma cells in vitro and in vivo, and that this data supports the future clinical evaluation of perifosine for the treatment of neuroblastoma tumors.
Juergen Engel, Ph.D., President and CEO of Aeterna Zentaris stated, "The data presented in this article are further proof of perifosine's great potential as an oral, novel, first-in- class anti-cancer treatment for multiple types of cancer, including neuroblastoma tumors for which there are currently no FDA approved drugs."
A copy of the article can be obtained at http://www.ncbi.nlm.nih.gov/pubmed/20463309.
Perifosine is a novel, potentially first-in-class, oral anticancer agent that modulates Akt, and a number of other key signal transduction pathways, including the JNK and MAPK pathways, all of 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.
In addition to the Phase 1 study in pediatric patients, perifosine is currently in Phase 3 registration trials in multiple myeloma and advanced colorectal cancer, under Special Protocol Assessment and Fast Track designation granted by the FDA for both indications. FDA has also granted perifosine orphan-drug status for multiple myeloma. Furthermore, the European Medicines Agency (EMA) has issued a positive Scientific Advice as well as a positive opinion for Orphan Medicinal Product designation for perifosine in multiple myeloma.
Perifosine is also in Phase 1 and 2 clinical development for several other tumor types.
Neuroblastoma is the most common pediatric solid tumor and is also the most frequently diagnosed neoplasm during infancy. Neuroblastoma accounts for more than 7% of malignancies in patients younger than 15 years and causes 15% of all pediatric oncology deaths. Activated Akt is believed to be highly expressed in poor prognosis neuroblastoma tumors. Infants, even those with metastatic disease, may experience complete regression of their disease with single low-dose chemotherapy or observation alone in carefully selected circumstances. However, poor prognosis patients, usually older than 18 months and who have extensive metastatic disease, may initially respond to intensive multimodality chemotherapy, but the tumors eventually recur and become resistant to chemotherapy. Approximately half of all neuroblastoma patients are diagnosed with high-risk poor prognosis disease, and these patients have an overall survival rate of less than 40%. Therefore, a major challenge is to improve the treatment efficacy in high-risk neuroblastoma patients.
There are currently no FDA approved drugs for the treatment of neuroblastoma.
About Aeterna Zentaris Inc.
Aeterna Zentaris Inc. is a late-stage drug development company specialized in oncology and endocrine therapy. News releases and additional information are available at www.aezsinc.com.
This press release contains forward-looking statements made pursuant to the safe harbor provisions of the U.S. Securities Litigation Reform Act of 1995. Forward-looking statements involve known and unknown risks and uncertainties, which could cause the Company's actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue R&D projects, the successful and timely completion of clinical studies, the ability of the Company to take advantage of business opportunities in the pharmaceutical industry, uncertainties related to the regulatory process and general changes in economic conditions. Investors should consult the Company's quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned not to rely on these forward-looking statements. The Company does not undertake to update these forward-looking statements. We disclaim any obligation to update any such factors or to publicly announce the result of any revisions to any of the forward-looking statements contained herein to reflect future results, events or developments except if we are required by a governmental authority or applicable law.
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