QUÉBEC CITY, Sept. 23, 2011 /PRNewswire/ - Aeterna Zentaris Inc. (NASDAQ: AEZS) (TSX: AEZ) (the "Company"), today announced positive interim data for the Phase 1 portion of its ongoing Phase 1/2 study in castration and taxane-resistant prostate cancer with its targeted cytotoxic luteinizing hormone releasing hormone (LHRH) analog, AEZS-108. The data were presented by Jacek Pinski, M.D, Associate Professor of Medicine at the Norris Comprehensive Cancer Center of the University of Southern California, during a poster session on Saturday, September 24, 2011, at the European Society of Medical Oncology (ESMO) Congress currently being held in Stockholm, Sweden. The trial is being supported by a three year grant of about US$1.5 million from the National Institutes of Health.
Dr. Pinski stated, "Results for the Phase 1 portion of our clinical trial exceeded our expectations. In addition to proving to be very safe, AEZS-108 also demonstrated impressive efficacy even at low doses."
Juergen Engel, Ph.D., President and CEO of Aeterna Zentaris commented, "We thank Dr. Pinski and his colleagues for the exciting outcome of this early study, including the elegant demonstration of drug internalization in circulating tumor cells of treated patients. We now look forward to the Phase 2 portion of this study which will have more emphasis on therapeutic activity. It will also be interesting to see the results from the correlative studies to further strengthen the rationale of this personalized treatment approach."
The Phase 1/2 Study
The poster (abstract # 294) entitled, "A Phase I/II Trial of AEZS-108 in Castration- and Taxane-Resistant Prostate Cancer", S.V. Liu, A.V. Schally, T. Dorff, S. Groshen, D. Hawes, D. Quinn, Y.C. Tai, N.L. Block, J. Engel, and J. Pinski, 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 patients with castration-resistant prostate cancer (CRPC) for which the presence of LHRH receptors has been confirmed. This is a single arm study with a Phase 1 lead-in to a Phase 2 clinical trial. The primary endpoint of the Phase 1 portion is safety. The primary objective of the Phase 2 portion is to evaluate the clinical benefit of AEZS-108 for these patients.
Up to 18 men were planned for the Phase 1 lead-in portion which follows a "3+3" model to confirm or modify, if needed, the dose established in a completed Phase 1 trial in women. Patients received AEZS-108 intravenously over 2 hours every 3 weeks for up to 6 cycles, until progression of the disease, unacceptable toxicity or patient withdrawal. Premedication included dexamethasone 8 mg. Maximal Prostate Specific Antigen (PSA) response was calculated using PSA Working Group 2 guidelines. Response Evaluation Criteria in Solid Tumors (RECIST, v. 1.1) was used to assess response for patients with measurable disease.
Results
Twelve patients entered the study, 3 patients each received AEZS-108 at the lower dose levels of 160 and 210 mg/m2, and 6 patients at 267 mg/m2. Data on 10 patients were presented; 2 patients were too early for evaluation. AEZS-108 was generally well tolerated and there were no dose limiting toxicities so far. The only grade 3 and 4 toxicities were hematologic in nature. There were no cases of bleeding or infections. To date, there have been three grade 4 toxicities (2 at 210 mg/m2, 1 at 267 mg/m2), all of which were asymptomatic. There have been six grade 3 toxicities including two cases of grade 3 anemia after repeated courses (cycles 5 and 6) and one case of febrile neutropenia that occurred during cycle 1.
Signs of therapeutic activity included 5 patients with PSA regression. One of these patients treated at the lowest dose level, received 8 treatment cycles because he demonstrated continued clinical benefit. Three out of 4 evaluable patients with radiologic evaluable disease achieved stable disease per RECIST.
Correlative studies
In correlative studies, the internalization of AEZS-108 was monitored in circulating tumor cells (CTCs) isolated from treated patients. CTCs were isolated from patients' blood and uptake of AEZS-108 was visualized via the autofluoresence of the doxorubicin moiety. Internalization was demonstrated in CTCs collected 1-3 hours and 24 hours after AEZS-108 infusion. These data demonstrate for the first time, the internalization of AEZS-108 in tumor cells of patients, thus, validating the principle of targeted tumor therapy with AEZS-108 in a clinical setting.
Conclusions
- AEZS-108 was well tolerated at all dose levels
- Early evidence of AEZS-108's anti-tumor activity even at low dose level
- Drug internalization was demonstrated in captured CTCs
- Phase 2 extension planned after completion of the toxicity assessment in the final dose level of the Phase 1 portion of the study.
To consult a copy of the poster, please click here.
About Prostate Cancer
According to the National Cancer Institute (NCI), prostate cancer is the second most prevalent type of cancer after lung cancer. The NCI estimates that 240,890 men will be diagnosed with and 33,720 men will die of prostate cancer in 2011, in the United States alone.
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 1/2 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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