Last updated on April 23, 2014 at 21:24 EDT

Aeterna Zentaris: Final Phase 2 Data Demonstrate Perifosine and Sorafenib Combination Therapy Well Tolerated by Heavily Pretreated Lymphoma Patients

December 11, 2012

Promising clinical response activity observed in patients with Hodgkin

QUÉBEC CITY, Dec. 11, 2012 /PRNewswire/ – Aeterna Zentaris Inc. (NASDAQ:
AEZS) (TSX: AEZ) today announced that final Phase 2 data demonstrated
that the combination of perifosine, its oral AKT inhibitor, and
sorafenib, was well tolerated by heavily pretreated patients with
relapsed/refractory lymphomas. Furthermore, promising clinical response
activity was observed in patients with classical Hodgkin Lymphoma
(“HL”), suggesting that this subgroup could represent the target
population for future studies. Data were presented yesterday by Anna
Guidetti, MD, of the Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, during a poster session at the American Society of
Hematology annual meeting in Atlanta, Georgia.

The Study

This investigator-driven Phase 2 trial sponsored by the Fondazione IRCCS Istituto Nazionale Tumori, involved 40 patients with relapsed/refractory lymphomas who had failed
second or subsequent-line salvage chemotherapy: there were 3 patients
with diffuse large B-cell lymphoma, 3 with follicular lymphoma, 1 with
Waldenstrom macroglobulinemia, 8 with chronic lymphocytic leukemia
(“CLL”) and 25 with classical Hodgkin lymphoma (“HL”). At study entry,
12 patients (30%) had relapsed and 28 (70%) refractory disease.
Treatment plan included an initial 4 week treatment with perifosine (50
mg BID, per os) to assess tolerability and tumor response.
Subsequently, patients achieving less than partial response (“PR”) were
given perifosine (50 mg BID, per os) combined with sorafenib (400 mg
BID, per os) until progression of disease (“PD”) or significant
clinical toxicity. Patients achieving at least a PR went off-study and
continued with perifosine (50 mg BID, per os) alone until PD or
clinical toxicity. Tumor response was assessed according to the revised
response criteria for malignant lymphoma of the International Working


Based on tumor response to the initial 4 week perifosine therapy, 36 of
40 patients who achieved less than PR were subsequently administered
the perifosine/sorafenib combination therapy. Median duration of
combination therapy was 4 months (range: 2-18). Four CLL patients who
achieved at least a PR with perifosine alone, went off-study and
continued with single-agent therapy with a median duration of response
of 10 months (range 4-21). The most common drug-related toxicities were
grade 1-2 diarrhea (25%), joint pain (22%), weight loss (19%), anemia
(17%), and thrombocytopenia (9%). Hand-foot skin reaction was observed
in 25% (grade 2) and 14% (grade 3) of patients. Grade 4 neutropenia was
observed in only 1 patient. Two responding patients experiencing
grade 3 pneumonitis discontinued treatment.

For the 36 patients treated with combination therapy, 8 (22%) PR, 15
(42%) stable disease (“SD”) and 13 (36%) PD were observed. Median time
to achieve PR was 4 months (range 1-8) and median duration of response
was 4 months (range 1-12). Median overall survival (“OS”) and
progression free survival (“PFS”) for all patients were 16 and 5
months, respectively.

For the 25 patients in the HL subgroup also receiving combination
therapy, the overall response-rate was 28%, with 7 PR; for HL patients,
median OS and PFS were 16 and 5 months respectively, as it was for all

A significant correlation between pErk and pAkt reduction during the
first 2 months of therapy and clinical response was demonstrated by
logistic regression model. The reduction of pErk and pAkt values
(i.e difference between baseline values vs 60 day values) was related
to a highly significant probability to observe a clinical response (p =
0.0003 and p = 0.005 for pErk and pAkt, respectively).


Combination of perifosine and sorafenib was well tolerated by heavily
pretreated lymphoma patients. Promising clinical response activity was
observed in relapsed/refractory HL patients, suggesting that this
subgroup could represent the target population for future studies.
Early reduction of pERK and pAK has a significant predictive value of
clinical response.

The poster, “Dual Targeted Therapy with the AKT Inhibitor Perifosine and the
Multikinase Inhibitor Sorafenib in Patients with Relapsed/Refractory
Lymphomas: Final Results of a Phase II Trial”
, A Guidetti, S. Viviani, A. Marchiano, A. Dodero, L. Farina, S.L.
Locatelli, D. Russo, P. Bulian, R. Sorasio, M. Di Nicola, L. Giordano,
P. Corradini, A.M. Gianni, C. Carlo-Stella, 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 for
multiple myeloma (“MM”) from the Food and Drug Administration (“FDA”)
and the European Medicines Agency (“EMA”), respectively. Perifosine
has also received Fast Track designation from the FDA for this same
indication. The ongoing Phase 3 trial in MM is conducted under a
Special Protocol Assessment from the FDA and positive Scientific Advice
from the EMA, with positive results from this trial expected to be
sufficient for registration in the US and Europe. Perifosine is also
being explored in combination therapy and in monotherapy in other
cancer indications. Aeterna Zentaris holds worldwide rights to
perifosine except for Japan, Korea and MENA (Middle East and North
Africa) region, where licensing rights have been granted to Yakult
Honsha, Handok Pharmaceuticals and Hikma Pharmaceuticals, respectively.

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: PR Newswire