Cancer Therapy Center

QUEBEC CITY, Nov. 27

PRNewswire-FirstCall

AEterna Zentaris Inc today disclosed additional positive top line Phase 1 results for its cytotoxic conjugate AN-152 in patients with gynaecological and breast cancers. Further data showed the compound’s good safety profile and established the maximum tolerated dose (MTD) at 267 mg/m(2) which will be the recommended dose for a Phase 2 trial. In addition to good safety data, the trial provided a hint of efficacy as disease stabilization and regression of lesions were observed at the 160 mg/m(2) and 267 mg/m(2) dose levels.

Dr. Jurgen Engel, Executive Vice President, Global R&D and Chief Operating Officer at AEterna Zentaris, stated, “This additional data provides further proof of concept that the chemical linkage of doxorubicin and the luteinizing hormone-releasing hormone part of the drug molecule is stable in human blood. Most importantly, we witnessed a good safety profile and a hint of efficacy enabling us to establish a suitable dose for further development of AN-152 in the treatment of various cancers.”

Gilles Gagnon, President and Chief Executive Officer at AEterna Zentaris added, “We are very pleased and now even more encouraged with the latest Phase 1 results for AN-152 which lend further credibility to our very promising oncology platform. By targeting patients suffering from ovarian and endometrial cancer with confirmed LHRH receptor status, we believe we may increase our chances of success for our Phase 2 program in these indications. This targeted approach is an additional example of personalized therapy which is becoming more and more the way of the future.”

About the AN-152 Phase 1 Trial in Gynaecological and Breast Cancers

This ongoing Phase 1 open-label, multi-center, dose-escalation, safety and pharmacokinetic study conducted in Europe, includes 17 patients suffering from breast, endometrial and ovarian cancers with proven luteinizing hormone-releasing hormone (LHRH) receptor status. Patients were administered AN-152 by intravenous infusion over two hours at dosages of 10, 20, 40, 80, 160 and 267 mg/m(2). Patients received at least two treatment courses, 21 days apart.

Results

Dose escalation was stopped at 267 mg/m(2), which is equimolar to a doxorubicin dose of 77 mg/m(2), and declared as maximum tolerated dose (MTD) due to dose-limiting although rapidly reversible hematoxicity (CTC grade 4 leucocytopenia/neutropenia) in two out of six patients. Pharmacokinetic (PK) analyses showed dose-dependent plasma levels of AN-152 and only minor (10%-30%) release of doxorubicin. One complete response (TBC by forthcoming CT scan) and two stable disease out of six patients at the 160 mg/m(2) dose level were reported, while at the 267 mg/ m(2) dose level, one partial response and three stable disease were observed from this group of seven patients.

Conclusion

Infusion of AN-152 is well tolerated in female patients. Disease stabilization and regression of lesions are promising signals for therapeutic activity of the cytotoxic LHRH analog, most probably through receptor-mediated uptake by tumor tissue. Because of the rapid reversibility of the potentially dose-limiting hematoxicity even in patients with multiple prior therapies, the dose of 267 mg/m(2) is going to be recommended for Phase 2 trials with ovarian and endometrial cancer as targeted indications. Ovarian and endometrial cancers are two forms of cancer where LHRH receptors are highly expressed.

Background

Human breast, endometrial and ovarian cancers commonly express receptors for luteinizing hormone-releasing hormone (LHRH-R). High-affinity binding sites for LHRH are found in 52% of human breast cancers, as well as in 80% of human ovarian and endometrial cancers. LHRH-R can be used for targeted chemotherapy with AN-152, in which doxorubicin is linked to (D-Lys(6))-LHRH. Safety pharmacology and toxicity studies in mice, rats and dogs demonstrated a significantly reduced cardiotoxic potential of AN-152 compared with doxorubicin, e.g. no QT prolongation, myocarditis or fibrosis in the appropriate models. The Phase 1 study assessed dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and pharmacokinetics (PK) of AN-152 given once every three weeks in patients with gynaecological and breast cancers.

About Cytotoxic Conjugate AN-152

Targeted cytotoxic peptide conjugates are hybrid molecules composed of a synthetic peptide carrier and a well-known cytotoxic product. The design of these products allows for the specific binding and selective uptake of the cytotoxic conjugates by the LHRH receptor-positive tumors. The binding of cytotoxic conjugates to cancerous cells that express these receptors results in an accumulation of the antiproliferative agent in the malignant tissue. This binding is followed by internalization and retention of the cytotoxic drug in the cells. Therefore, since they target specific cells, cytotoxic conjugates are much less toxic, have less side-effects and are more effective in vivo than the respective radicals in inhibiting tumor growth.

About AEterna Zentaris Inc.

AEterna Zentaris Inc. is a growing global biopharmaceutical company focused on endocrine therapy and oncology, with proven expertise in drug discovery, development and commercialization.

News releases and additional information are available at www.aeternazentaris.com.

Forward-Looking Statements

This press release contains forward-looking statements made pursuant to the safe harbor provisions of the U.S. Securities Litigation Reform Act of 1995. Forward-looking statements involve known and unknown risks and uncertainties, which 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 the 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.

Lung cancer patients treated with an experimental new drug in addition to standard chemotherapy lived more than one third longer than patients treated with chemotherapy alone, according to new data posted at 2Breathe.net, as they review a small phase II study carried out by a British biotech company, Antisoma plc, enrolled 70 patients with non-small cell lung cancer, the most common type of lung cancer. 

Researchers reported that patients treated with AS1404 on top of standard chemotherapy lived 14 months compared to 8.8 month for patients who solely received chemotherapy alone.

AS1404 is one of a new class of drugs called Vascular Disrupting Agents (VDAs) that work by selectively destroying established tumor blood vessels, the blood supply that enables a tumor to survive and grow.

Researchers said AS1404 is able to distinguish between the tumor’s blood supply and the more permeable and less-well organized capillary network of healthy organs.

If the early results with AS1404 are confirmed in larger phase III trials, this would be a significant increase in life expectancy for patients suffering from lung cancer, which has one of the lowest survival outcomes of any cancer.

The referenced study is one of three currently underway testing various aspects of AS1404. Positive data has been announced in a trial testing its use in prostate cancer, as well as promising early data from an ongoing ovarian cancer trial. If approved for use, Antisoma is expected to license AS1404 to a number of different companies.

UPI is among those who point to a new study conducted at Massachusetts General in Boston that found that RF was able to kill Ovarian cancer cells that had spread to the liver:

Six patients with advanced ovarian cancer underwent radiofrequency ablation to destroy metastatic disease in their liver, and the procedure successfully eliminated all tumor cells in five of the six patients after only one session.

Gervais said her team followed the patients for between eight months and 3.3 years, and four of the five did not develop recurrent disease in the area the procedure destroyed.

“The treatment of ovarian cancer requires multi-modality approaches, including surgery and chemotherapy,” said Gervais, “but our study indicates that a small number of patients may benefit from radiofrequency ablation instead of repeated surgery.”

Like many new treatments, RF requires additional types of treatments to be completely effective, but this is a promising development for women diagnosed with ovarian cancer.