Aeterna Zentaris: Data Demonstrate that Perifosine Combined with Temsirolimus Was Well Tolerated in Phase 1 Trial in Malignant Glioma
QUÃ‰BEC 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
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
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
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.
SOURCE AETERNA ZENTARIS INC.