Aeterna Zentaris announces results from perifosine Phase 1 trial on multiple myeloma

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 multiple myeloma.

The Study

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 (clinicaltrials.gov NCT00415064).

Results

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 reported.

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."