QUÉBEC CITY, Nov. 19, 2012 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company") today announced that perifosine, its oral AKT inhibitor, combined with temsirolimus ("TEM"), was well tolerated in an investigator driven Phase 1 clinical trial in recurrent or progressive malignant glioma ("MG"). Data were presented over the weekend by Thomas J. Kaley, MD, Director, Neuro-Oncology Fellowship Program at Memorial Sloan-Kettering Cancer Center, during a poster session at the Society of Neuro-Oncology annual meeting in Washington D.C.
The trial involved 32 patients with recurrent or progressive (glioblastoma (16), anaplastic astrocytoma (7), anaplastic oligodendroglioma (7), and transformed low-grade gliomas (2)), with median Karnofsky Performance Status ("KPS") 80 (range, 60-100). Twenty-one patients were refractory to bevacizumab or other anti-VEGF/VEGFR therapy. The dose of TEM was escalated in each cohort using standard 3 + 3 design from 15 mg to 170 mg administered once weekly. The dose of perifosine was a 600 mg loading dose on day 1, followed by a 100 mg nightly dose, for dose level 1 through dose level 6. At dose level 7, the loading dose was increased to 900 mg, followed by a 100 mg nightly dose.
The trial is currently accruing to dose level 5 (115 mg) after 2 dose-limiting toxicities ("DLT") in the dose level 7 (170 mg) and dose level 6 (170 mg) expansion cohorts. Maximum tolerated dose ("MTD") was not defined. Thirty-one patients were evaluable for toxicity. There were 5 DLTs: thrombocytopenia (3), intra-cerebral hemorrhage (1), and lung infection (1). Only one grade 4 toxicity (thrombocytopenia) was reported. Most frequent grade 3 non dose-limiting hematologic toxicities were lymphopenia (7), hyperglycemia (4), lung infection (4), and hypophosphatemia (3). Notable grade 2 toxicities were hypophosphatemia (14), hypocholesterolemia (13), and hypertriglyceridemia (11).
Preliminary survival results demonstrated that median overall survival was 7.4 months. There were 27 radiographic responses: complete response (0), partial response (2), stable disease (13) and progressive disease (12).
Combination therapy with TEM ≥ 115 mg weekly and perifosine 100 mg daily (following 600 mg load) was well tolerated in heavily pre-treated adults with recurrent MGs. Accrual ongoing at dose level 5 and MTD has not yet been defined.
The poster, "Phase I trial of Temsirolimus (TEM) and Perifosine (PER) for Recurrent or Progressive Malignant Glioma (MG)", T. J. Kaley, E. Pentsova, A. Omuro, I. K. Mellinghoff, C. Nolan, I. Gavrilovic, L. M. DeAngelis, E. Holland, M. E. Lacouture, E. Ludwig, A. B. Lassman, can be viewed at this link.
Perifosine is a novel, oral anticancer treatment that inhibits Akt activation in the phosphoinositide 3-kinase (PI3K) pathway. It has been granted orphan drug and orphan medicinal product designations from both the FDA and EMA for multiple myeloma. Perifosine has also received Fast Track designation from the FDA and positive Scientific Advice from the EMA with results from the Phase 3 trial in multiple myeloma expected to be sufficient for registration in Europe, as well as in North America. Perifosine is also being explored in combination therapy and in monotherapy in other cancer indications. Aeterna Zentaris holds rights to perifosine for North America and Europe, while rights have been licensed to Yakult Honsha for Japan, to Handok for Korea, and to Hikma Pharmaceuticals for the MENA (Middle East and North Africa) region.
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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