Aeterna Zentaris: Data Demonstrate that Perifosine Combined with Temsirolimus
Was Well Tolerated in Phase 1 Trial in Malignant Glioma
QUÉBEC CITY, Nov. 19, 2012
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 (170mg) 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
Preliminary survival results demonstrated that median overall survival was 7.4
months. There were 27radiographic 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
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
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 (MiddleEast 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
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
SOURCE AETERNA ZENTARIS INC.
Ginette Beaudet Vallières
Investor Relations Coordinator
(418) 652-8525 ext. 265
Director of Communications
(418) 652-8525 ext. 406
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