Aeterna Zentaris: Phase 2 Data Demonstrate Perifosine's Promising Efficacy in the Treatment of Advanced Leukemia, Lymphoma and Multiple Myeloma

In two Phase 2 studies, perifosine achieves objective responses and high rates of stable disease as a single-agent in the treatment of Chronic Lymphocytic Leukemia (CLL), and in combination with sorafenib in the treatment of relapsed/refractory Hodgkin's Lymphoma (HL)

QUÉBEC CITY, Dec. 6 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: AEZS,TSX: AEZ) today announced Phase 2 data presented for the first time on perifosine, its lead novel oral anti-cancer compound, showing promising clinical activity, safety and tolerability in patients with advanced chronic lymphocytic leukemia (CLL) and Hodgkin's lymphoma (HL). The data were presented over the weekend at the 52^nd Annual Meeting of the American Society of Hematology (ASH) in Orlando, Florida.

Juergen Engel, Ph.D., President and CEO of Aeterna Zentaris stated, "The encouraging data in advanced leukemia and Hodgkin's lymphoma presented at the ASH meeting, confirm perifosine's efficacy and safety as a novel, oral anti-cancer agent not only in combination therapy with approved anti-cancer agents but also as a single agent therapeutic. Data also showcase perifosine's potential beyond the current Phase 3 registration trials in metastatic colorectal cancer and multiple myeloma."

Key highlights from the two Phase 2 poster presentations are as follows:

Abstract # 2861: "Clinical Activity and Safety of the Combined Therapy with the AKT Inhibitor Perifosine and the Multikinase Inhibitor Sorafenib In Heavily Pretreated Patients with Relapsed/Refractory Lymphomas: Preliminary Results of a Phase II Trial" 

Study Background 

In this Phase 2 study, 26 patients were enrolled with advanced lymphoma (6 NHL, 4 CLL, 1 Waldenstrom's Macroglobulinemia and 15 Hodgkin's lymphoma).  73% of patients were previously refractory to their prior therapy, with 85% of patients having had 4 or more prior therapies. Perifosine (50 mg BID) was started as a single agent for 28 days; after 28 days, patients achieving partial response (PR) or better were continued on single agent perifosine.  Patients achieving less than a PR were given the combination of perifosine (50 mg BID) plus sorafenib (Nexavar^®) at 400 mg BID.

Results

All of the 4 CLL patients in the study achieved a partial response on single-agent perifosine within one month of treatment and remained on perifosine single agent.  Response durations for each of the 4 patients were 4, 8, 9+ and 12 months. The remaining 22 patients were administered the combination with sorafenib, where 5 of the 15 (33%) Hodgkin's lymphoma patients achieved a partial response with a median response duration of 9 months.  An additional 6 patients receiving the combination (40%) achieved stable disease.  The combination was well tolerated with no unexpected safety events.

The investigators concluded that perifosine in combination with sorafenib has significant anti-lymphoma activity in relapsed/refractory HL, and that perifosine as a single agent induced prolonged responses in high-risk, heavily pretreated CLL patients.

Abstract # 1842:  "Pre-Clinical and Interim Results of a Phase II Trial of Perifosine In Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)"

Study Background: 

In this Phase 2 study, 12 patients with advanced CLL began treatment with single agent perifosine at 50 mg BID. Patients on study were heavily pre-treated having had a median of 4 prior lines of therapy with 75% of patients classified as Rai stage IV.

Results

1 patient achieved a partial response (5 months on treatment) and 5 additional patients achieved stable disease (median duration of 4.25 months), for an overall 50% clinical benefit rate (PR + SD).  Perifosine was well tolerated with minimal dose modifications.

Abstract # 3064: "Final Phase I Results of Perifosine In Combination with Lenalidomide and Dexamethasone In Patients with Relapsed or Refractory Multiple Myeloma (MM)"

Additionally, the final data set from the Phase 1 study of perifosine + lenalidomide (Revlimid^®) + dexamethasone were also presented during the ASH meeting.  The final data showed a 73% objective response rate (minimal response or better) with a 50% PR or better, a median Progression-Free Survival of 10.8 months, and a median duration for Overall Survival of 30.6 months. The myeloma investigators concluded that perifosine in combination with lenalidomide + dexamethasone was well tolerated even at the highest doses used, and demonstrated encouraging clinical activity and survival.

A copy of the above referenced abstracts can be viewed online through the ASH website at www.hematology.org

About Perifosine

Perifosine is a novel, oral anticancer treatment that inhibits Akt activation in the phosphoinositide 3-kinase (PI3K) pathway. The product works by interfering with membranes of cancer cells thereby inhibiting Akt signaling which then affects cell death, growth, differentiation and survival. Perifosine, in combination with chemotherapeutic agents, is currently being studied for the treatment of multiple myeloma, colorectal cancer and other cancers, and is the most advanced anticancer compound of its class in late-stage development. Perifosine as monotherapy, is being explored in other indications. The US Food & Drug Administration ("FDA") has granted perifosine orphan-drug designation in multiple myeloma and neuroblastoma, and Fast Track designations in both multiple myeloma and refractory advanced colorectal cancer. Additionally, an agreement was reached with the FDA to conduct the Phase 3 trials in both of these indications under a Special Protocol Assessment. Perifosine has also been granted orphan medicinal product designation from the European Medicines Agency ("EMA") in multiple myeloma. Furthermore, perifosine has received positive Scientific Advice from the EMA for both the multiple myeloma and advanced colorectal cancer programs, with ongoing Phase 3 trials for these indications expected to be sufficient for registration in Europe. Perifosine rights have been licensed to Keryx Biopharmaceuticals for North America and to Handok for Korea.

About Aeterna Zentaris Inc.

Aeterna Zentaris is a late-stage oncology drug development company currently investigating potential treatments for various cancers including colorectal, ovarian, endometrial cancer and multiple myeloma. The Company's innovative approach of "personalized medicine" means tailoring treatments to a patient's specific condition and to unmet medical needs. Aeterna Zentaris' deep pipeline is drawn from its proprietary discovery unit providing the Company with constant and long-term access to state-of-the-art therapeutic options. 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 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.