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.