QUÉBEC CITY, June 5, 2012 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company") today announced that Phase 1 trial results for the Company's oral anticancer compound, perifosine, in multiple myeloma, have been published in the online May 2012 issue of the British Journal of Haematology. The article outlines the safety profile and encouraging clinical activity of perifosine when combined with lenalidomide and dexamethasone in relapsed and relapsed/refractory multiple myeloma.
Thirty-two patients were enrolled in this single-arm, open label Phase 1 trial across 4-dose cohorts. Patients received escalating doses of perifosine 50-100 mg daily and lenalidomide 15-25 mg once daily on days 1-21 of each 28-day cycle, plus dexamethasone 20-40 mg weekly thereafter, as indicated. The primary objectives of the trial were to determine the safety, maximum tolerated dose (MTD) and response -rate (clinicaltrials.gov NCT00415064).
Among 30 evaluable patients for efficacy, 73% achieved a minimal response or better, including 50% with a partial response or better. Median progression-free survival was 10.8 months and median overall survival was 30.6 months.
Among the 31 evaluable patients for safety and tolerability, the most common all-causality grade 1-2 adverse events were fatigue (48%) and diarrhea (45%), and grade 3-4 adverse events were neutropenia (26%), hypophosphataemia (23%), thrombocytopenia (16%), and leucopenia (13%). No grade 3-4 peripheral neuropathy or deep vein thrombosis were reported.
Exploratory pharmacodynamic study data suggest that the clinical efficacy of perifosine + lenalidomide + dexamethasone is positively associated with phospho-Akt; the activity of the 3-drug combination appeared to be greater in patients with higher baseline phospho-Akt. Although this observation is based on just a few patients, the correlative data could represent the first steps towards the rational selection of individualized therapy with Akt inhibitors. The data also suggest that perifosine may be particularly effective in patients with Akt-dependent multiple myeloma, a subgroup of multiple myeloma (Zollinger et al,2008). Additional studies are ongoing to investigate the potential relationship between perifosine activity and phospho-Akt. Findings may show whether patients with an activated Akt genotype would benefit in particular from the addition of perifosine, therefore raising the possibility of individualized therapy according to a patient's phospho-Akt status. The authors concluded: "Perifosine + lenalidomide + dexamethasone was well tolerated and demonstrated encouraging clinical activity in relapsed and relapsed/refractory multiple myeloma".
Juergen Engel, PhD, President and CEO of Aeterna Zentaris stated, "Results of this study including the new exploratory pharmacodynamic data are one of the reasons which encouraged us to continue our Phase 3 study with perifosine in multiple myeloma."
These data were presented previously; see Blood (ASH Annual Meeting Abstracts) 116: 2010 (abstract 3064).
About Multiple Myeloma
Multiple myeloma is the second most common blood cancer. According to Decision Resources, there will be approximately 180,830 cases of multiple myeloma diagnosed in the main G7 markets in 2012. Research shows that the majority of patients diagnosed with multiple myeloma are age 65 and older. Approximately 2,500 more males are diagnosed with this cancer than females each year.
Perifosine is a novel, oral anticancer compound that inhibits Akt activation in the phosphoinositide 3-kinase (PI3K) pathway. It works by interfering with membranes of cancer cells, thereby inhibiting Akt signaling which then affects cell death, growth, differentiation and survival. Perifosine is currently in a Phase 3 trial in multiple myeloma. In this indication, it has been granted Orphan Drug and Fast Track designations by the Food and Drug Administration. It has also received positive Scientific Advice and Orphan Medicinal Product designation from the European Medicines Agency. Rights for perifosine have been out licensed to Yakult Honsha Co. Ltd. for Japan, to Handok Pharmaceuticals Co. Ltd. for Korea and to Hikma Pharmaceuticals PLC for the Middle East and certain countries in North Africa. Aeterna Zentaris holds rights for the rest of the world.
About Aeterna Zentaris
Aeterna Zentaris is an oncology and endocrinology drug development company currently investigating treatments for various unmet medical needs. The Company's pipeline encompasses compounds at all stages of development, from drug discovery through to marketed products. For more information please visit www.aezsinc.com.
This press release contains forward-looking statements made pursuant to the safe harbour provisions of the U.S. Securities Litigation Reform Act of 1995. Forward-looking statements involve known and unknown risks and uncertainties that 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 risk that safety and efficacy data from any of our Phase 3 trials may not coincide with the data analyses from previously reported Phase 1 and/or Phase 2 clinical trials, 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 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, unless required to do so by a governmental authority or by applicable law.
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