Aeterna Zentaris: Final Phase 2 Data Demonstrate Perifosine and
Sorafenib Combination Therapy Well Tolerated by Heavily Pretreated
Lymphoma Patients
Promising clinical response activity observed in patients
with Hodgkin lymphoma
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 Group.
Results
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 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.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).
Conclusion
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 AETERNA ZENTARIS INC.