Aeterna Zentaris Inc. (NASDAQ:
AEZS) (TSX: AEZ) (the "Company") today announced that Phase 1 trial
results for the Company's oral anticancer compound, perifosine, in
multiple myeloma, have been published in the online May 2012 issue of
the British Journal of Haematology. The article outlines the safety
profile and encouraging clinical activity of perifosine when combined
with lenalidomide and dexamethasone in relapsed and relapsed/refractory
Thirty-two patients were enrolled in this single-arm, open label Phase 1
trial across 4-dose cohorts. Patients received escalating doses of
perifosine 50-100 mg daily and lenalidomide 15-25 mg once daily on
days 1-21 of each 28-day cycle, plus dexamethasone 20-40 mg weekly
thereafter, as indicated. The primary objectives of the trial were to
determine the safety, maximum tolerated dose (MTD) and response -rate
Among 30 evaluable patients for efficacy, 73% achieved a minimal
response or better, including 50% with a partial response or better.
Median progression-free survival was 10.8 months and median overall
survival was 30.6 months.
Among the 31 evaluable patients for safety and tolerability, the most
common all-causality grade 1-2 adverse events were fatigue (48%) and
diarrhea (45%), and grade 3-4 adverse events were neutropenia (26%),
hypophosphataemia (23%), thrombocytopenia (16%), and leucopenia (13%).
No grade 3-4 peripheral neuropathy or deep vein thrombosis were
Exploratory pharmacodynamic study data suggest that the clinical
efficacy of perifosine + lenalidomide + dexamethasone is positively
associated with phospho-Akt; the activity of the 3-drug combination
appeared to be greater in patients with higher baseline phospho-Akt.
Although this observation is based on just a few patients, the
correlative data could represent the first steps towards the rational
selection of individualized therapy with Akt inhibitors. The data also
suggest that perifosine may be particularly effective in patients with
Akt-dependent multiple myeloma, a subgroup of multiple myeloma
(Zollinger et al,2008). Additional studies are ongoing to investigate the potential
relationship between perifosine activity and phospho-Akt. Findings may
show whether patients with an activated Akt genotype would benefit in
particular from the addition of perifosine, therefore raising the
possibility of individualized therapy according to a patient's
phospho-Akt status. The authors concluded: "Perifosine + lenalidomide +
dexamethasone was well tolerated and demonstrated encouraging clinical
activity in relapsed and relapsed/refractory multiple myeloma".
Juergen Engel, PhD, President and CEO of Aeterna Zentaris stated,
"Results of this study including the new exploratory pharmacodynamic
data are one of the reasons which encouraged us to continue our Phase 3
study with perifosine in multiple myeloma."