Aeterna presents data on AEZS-108 Phase 2 study for endometrial cancer at EORTC-NCI-AACR Symposium

Nov 18 2010

Aeterna Zentaris Inc. (Nasdaq: AEZS; TSX: AEZ) (the "Company"), earlier today, presented Phase 2 positive efficacy and safety data for its compound, AEZS-108, in advanced endometrial cancer. The trial was conducted by the German AGO Study Group and centers in Bulgaria. The presentation was made by Prof. Günter Emons, Chairman, Department of Obstetrics & Gynaecology Georg-August University Göttingen, Germany during a poster session at the 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics currently being held in Berlin, Germany.

"The safety and efficacy of AEZS-108 in our study on advanced endometrial cancer was very encouraging," commented Prof. Günter Emons. "We must keep in mind that we used AEZS-108 as a single agent treatment only, and still achieved good rates of objective response and disease stabilization. Importantly from the patients' point of view, overall survival was similar to what has been reported with more aggressive and less well tolerated combination chemotherapy regimens."

Juergen Engel, Ph.D., President and CEO of Aeterna Zentaris added, "We would first like to thank Dr. Emons and all those involved in this trial for their dedicated work. These exciting positive results in endometrial cancer along with positive data for ovarian cancer disclosed earlier this year, reaffirm AEZS-108's potential as a novel targeted approach for the treatment of cancer. We now look forward to the further late-stage development of AEZS-108 for the benefit of women battling gynaecological cancers."

The Study

The poster (abstract #378) entitled, "Phase II study of AEZS-108, a targeted cytotoxic LHRH analog, in patients with LHRH receptor positive endometrial cancer", G. Emons, J. Sehouli, G. Gorchev, A. Hristamian, A. Staehle, LC. Hanker, P. Wimberger, M.W. Beckmann, V. Taskova, and C. Gruendker for the AGO Study Group, Germany, details the use of AEZS-108, the Company's targeted cytotoxic drug in which doxorubicin, a well known chemotherapeutic agent, is linked to [D-Lys(6)]-luteinizing hormone releasing hormone (LHRH), in women with histologically confirmed LHRH-R positive advanced (FIGO III or IV) or recurrent endometrial cancer. Patients received a recommended dose of 267 mg/m² by intravenous infusion over 2 hours, with retreatment every 3 weeks, for up to 6 courses. Response rate per Response Evaluation Criteria in Solid Tumors (RECIST) was defined as primary endpoint. Secondary endpoints were safety, time-to-progression (TTP) and overall survival (OS).

Results

In all, 44 patients entered the study. Of these, 1 patient was withdrawn prior to start of treatment and 2 patients entered as replacement for patients withdrawn for reasons other than progressive disease. Of 43 patients treated with AEZS-108, 39 were evaluable for efficacy. Responses confirmed by independent review included 2 patients with complete response (CR; 5.1%), 10 patients with partial response (PR; 25.6%), and 17 patients with stable disease (SD; 43.6%). Based on those data, an Overall Response Rate (ORR = CR+PR) of 30.8 % and a Clinical Benefit Rate (CBR = CR+PR+SD) of 74.4% can be estimated. Responses were also achieved in patients with prior chemotherapy, 1 CR, 1 PR and 2 SDs in 8 of the patients pre-treated with platinum/taxane regimens. Median time to progression (TTP) and overall survival (OS) were 7 months (30 weeks) and 14.3 months (62 weeks), respectively.

Overall, tolerability of AEZS-108 was good and commonly allowed retreatment as scheduled. Only one patient (2%) had a dose reduction, and 17 (8%) courses were given with a delay, including also 11 cases in which delay was not related to toxicity. Severe (Grade 3 or 4) toxicity was mainly restricted to rapidly reversible hematologic toxicity (leukopenia/neutropenia) associated with fever in 1 case only, a patient who had been treated only 3 weeks after a surgery. Good tolerability of AEZS-108 was also reflected by a low rate of severe possibly drug-related non-hematological adverse events and which included single cases (2.4%) each of nausea, diarrhea, fatigue, general health deterioration (Grade 4), creatinine elevation, and blood potassium decrease. No cardiac toxicity was reported.

Conclusion

• AEZS-108 at a dosage of 267 mg/m² every 3 weeks was active and well tolerated in patients with endometrial cancer.
• Hematological toxicity was rapidly reversible, and non-hematological toxicities were usually not severe, causing few deviations from scheduled treatment.
• The objective response rate of 31% compares well with those of single agent platinum or taxane treatment; responders included patients pre-treated with platinum/taxane combination.
• In addition, the rate of stable disease was 44%, resulting in a Clinical Benefit Rate of 74%.
• The overall survival after single agent AEZS-108 is similar to that reported for modern triple combination chemotherapy, but was achieved with lower toxicity.