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

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

PR Newswire

QUÉBEC CITY, Dec. 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 1patient. Two responding patients
experiencing grade3 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 patients.

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.edifference
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 asignificant 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 hasalso 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

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.



Investor Relations
Ginette Beaudet Vallières
Investor Relations Coordinator
(418) 652-8525 ext. 265

Media Relations
Paul Burroughs
Director of Communications
(418) 652-8525 ext. 406
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