Aeterna Zentaris Inc. (NASDAQ:
AEZS) (TSX: AEZ) (the "Company") today announced that Phase 1 trial
results for its oral PI3K/Akt inhibitor, perifosine, showed the drug's
activity against chemo-resistant and radio-resistant neuroblastoma,
while allowing good quality of life and sparing vital organs.
Neuroblastoma is a type of childhood cancer which usually begins in
nerve tissues. Data were presented yesterday by Brian H. Kushner, MD,
of the Memorial Sloan-Kettering Cancer Center in New York, during a
poster session at the Advances in Neuroblastoma Research Conference
which is being held in Toronto, Canada.
This was an open-label dose-escalating Phase 1 trial to assess toxicity
and efficacy of perifosine, given in monotherapy to patients with
neuroblastoma (clinicaltrials.gov NCT00776867). Patients were dosed using 50mg tablets and received a loading dose
(100-200mg/m2) of perifosine on day 1, followed by daily maintenance doses (50-75mg/m2) until progressive disease or dose-limiting toxicity. Disease
evaluation was every 8 weeks.
The poster reported on the outcome of 24 patients treated to date;
patients had a median age of 8.7 years (range 4.7 to 33.5) and a median
disease duration of 4.6 years (range 2.5 to 8.0). Three patients were
treated for neuroblastoma refractory to primary therapy, and 21 for
neuroblastoma resistant to salvage therapy after 1 to 5 (median 2)
prior relapses. Prior therapy included high-dose conventional induction
and 2nd line chemotherapy (all patients); myeloablative chemotherapy and stem
cell transplantation (10 patients) and/or targeted radiotherapy with
I-131-MIBG (9 patients).
Anti-neuroblastoma activity was evident by a 50% progression-free
survival rate at 12 months (Standard Error ±11%) and included 1
complete remission (CR) based on a normalized MIBG scan and 3 patients
with improved MIBG scan and normalized bone marrow histology over
prolonged follow-up (up to 37+months). No significant toxicity was
seen, in particular no grade 3 problems, and no safety issues were
encountered in 6 patients who started treatment with pre-existing
thrombocytopenia and/or grade 3 elevations in liver enzymes.
Perifosine was well tolerated, without major toxicity - hence,
compatible with good quality of life;
Perifosine monotherapy may help in progression-free survival of patients
with persistent/stable MIBG-positivity in skeletal sites;
Perifosine may have a possible role with chemotherapy, radiation
therapy, and/or other agents active in PI3K/Akt pathway.
Juergen Engel, PhD, President and CEO at Aeterna Zentaris stated, "These
data again emphasize perifosine's anticancer activity, as was the case
earlier this week with the article published in Cancer, outlining perifosine's anticancer activity in renal cell carcinoma. On
both occasions, the authors alluded to perifosine's potential as a
combination therapy which further supports our current Phase 3 trial in
multiple myeloma in which perifosine is used in combination with
bortezomib and dexamethasone."