Aeterna Zentaris: Data Demonstrate that Perifosine Combined with
Temsirolimus Was Well Tolerated in Phase 1 Trial in Malignant
Glioma
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 Study
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.
Results
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).
Conclusion
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.
About Perifosine
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.
Forward-Looking Statements
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.
SOURCE AETERNA ZENTARIS INC.