Encouraging data observed in overall survival and tolerability
Company has requested Parallel Scientific Advice from FDA and EMA for pivotal trial
QUÉBEC CITY, Sept. 14, 2011 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the “Company”) earlier today, presented positive final Phase 2 efficacy and safety data for its targeted cytotoxic luteinizing hormone releasing hormone (LHRH) analog, AEZS-108, in advanced endometrial cancer. The trial, chaired by Prof. Günter Emons, Chairman, Department of Obstetrics & Gynaecology, Georg-August University Göttingen, Germany, was conducted by the German AGO Study Group and centers in Bulgaria. The presentation was made by Pauline Wimberger, M.D., Assistant Director, Gynaecology and Obstetrics Clinic, University of Duisburg-Essen, Germany, during a poster session at the 17th International Meeting of the European Society of Gynaecological Oncology (ESGO) currently being held in Milan, Italy.
“The safety and efficacy of AEZS-108 in our study on advanced endometrial cancer was very encouraging”, commented Dr. Wimberger. “Although used as a single agent treatment only, AEZS-108 achieved good response rates and disease stabilization. Personally, I was impressed to see three responses in the five patients treated at my institution, including one long-lasting complete response.”
Juergen Engel, Ph.D., President and CEO of Aeterna Zentaris added, “We would first like to thank Dr. Wimberger and all those involved in this trial for their dedicated work which is now being presented to the international gynaecological community. We are very excited about these final results achieved with AEZS-108 alone, which compare favourably with those usually seen with more aggressive and less well tolerated combination regimens for endometrial cancer. On this basis, we have requested Parallel Scientific Advice from both the FDA and the EMA for the further pivotal development of AEZS 108 in this indication in the upcoming months.”
The Study
The poster (abstract #247) entitled, “AGO-GYN 5 - (Phase II) with AEZS-108, a targeted cytotoxic LHRH analog in patients with LHRH receptor positive endometrial cancer”,Wimberger P, Gorchev G, Hanker L, Stähle A, Hristamian A, Beckmann MW, Dall P, Gründker C, Hilpert F, Sehouli J, Harter P, Taskova V, Emons G, details the use of AEZS-108, the Company’s targeted cytotoxic analog in which doxorubicin, a well known chemotherapeutic agent, is linked to [D-Lys(6)]-LHRH, in women with histologically confirmed LHRH-R positive advanced (FIGO III or IV) or recurrent endometrial cancer. Patients received AEZS-108 by intravenous infusion at a dose of 267 mg/m2, once every 3 weeks. The primary endpoint was the response rate as defined by the Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints included safety, time-to-progression (TTP) and overall survival (OS).
Results
In all, of 43 patients treated with AEZS-108, 39 were evaluable for efficacy. Efficacy confirmed by independent response review included 2 complete responses (CR), 10 partial responses (PR), and 17 patients with disease stabilization (SD). Based on those data, the estimated Overall Response Rate (ORR = CR+PR) was 30.8% and the Clinical Benefit Rate (CBR = CR+PR+SD) was 74.4%. Responses in patients previously treated with chemotherapy included 1 CR, 1 PR and 2 SDs in 8 of the patients with prior use of platinum/taxane regimens. Median TTP and OS were 7 months and 13.7 months, respectively.
Overall, tolerability of AEZS-108 was good and commonly allowed retreatment as scheduled. Only one patient had a dose reduction, and less than 10% of treatment courses were postponed, including more than half of the cases in which the delay was not related to toxicity. Severe (Grade 3 or 4) toxicity was mainly restricted to rapidly reversible leukopenia and neutropenia, associated with fever in only 1 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 non-hematological possibly drug-related adverse events which included single cases each of nausea, diarrhea, fatigue, general health deterioration, 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 30.8% 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 43.6%, resulting in a Clinical Benefit Rate of 74.4%.
- The overall survival after single agent AEZS-108 is similar to that reported for modern triple combination chemotherapy, but was achieved with lower toxicity.
To consult a copy of the poster, please click here.
About Endometrial Cancer
This year, the American Cancer Society estimates that more than 43,000 cases of endometrial cancer - tumors in the lining of the uterus and the glands of the endometrium - will be diagnosed in the United States. Symptoms can include unexplained vaginal bleeding, painful urination, painful intercourse and soreness in the pelvic area. There is no routine test to identify endometrial cancer. Treatment options include surgery, radiation therapy, hormone therapy and chemotherapy; however, there are new treatments in development that work by targeting and destroying cancerous cells.
About AEZS-108
AEZS-108 represents a new targeting concept in oncology using a hybrid molecule composed of a synthetic peptide carrier and a well-known chemotherapy agent, doxorubicin. AEZS-108 is the first intravenous drug in a clinical study that directs the chemotherapy agent specifically to LHRH-receptor expressing tumors, resulting in more targeted treatment with less damage to healthy tissue. The product has successfully completed Phase 2 studies for the treatment of endometrial and ovarian cancer, and is also in Phase 2 trials in prostate and bladder cancer. A pivotal trial in endometrial cancer is expected to be initiated by the end of 2011. AEZS-108 has been granted orphan-drug designation by the FDA and orphan medicinal product designation from the EMA for the treatment of ovarian cancer. Aeterna Zentaris owns the worldwide rights to AEZS-108.
About Aeterna Zentaris Inc.
Aeterna Zentaris is a late-stage oncology drug development company currently investigating potential treatments for various cancers including colorectal, multiple myeloma, endometrial, ovarian, prostate and bladder cancer. 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 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.
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