AETERNA/ZENTARIS TO PRESENT DETAILED POSITIVE PHASE II DATA ON CETRORELIX AND NEW PRECLINICAL DATA ON PERIFOSINE DURING INVESTOR AND ANALYST DAY IN NEW YORK CITY
AEterna Laboratories, along with its wholly owned subsidiary Zentaris GmbH, will present detailed positive phase II data on cetrorelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, in endometriosis and benign prostatic hyperplasia (BPH) during the investor and analyst day being held in New York today. These results will form the basis for further development of cetrorelix through collaboration with Solvay Pharmaceuticals, the company's worldwide (ex-Japan) exclusive development and marketing partner. In addition, AEterna/Zentaris will present new encouraging preclinical data on perifosine, the company's novel, first-in-class, oral AKT inhibitor, in combination with radiation therapy, supporting the continuing clinical development of perifosine in combination with radiotherapy as a potential treatment for multiple types of cancer. AEterna/Zentaris plans to initiate phase II trials of perifosine in combination with radiotherapy, through the continuing collaboration with the Netherlands Cancer Institute of Amsterdam, after presenting phase I results at the American Society of Clinical Oncology (ASCO) annual meeting in June, 2004.
Cetrorelix in endometriosis
A total of three phase II trials, of which one was double-blind and placebo-controlled, were conducted to evaluate different dosage regimens and formulations of cetrorelix in patients with endometriosis. Highly encouraging results were seen in the double-blind, placebo-controlled trial in two groups of 25 patients with endometriosis who received either placebo or depot formulation of cetrorelix by two intramuscular injections with a one-month interval. Assessment of pain (including dysmenorrhea, dyspareunia and chronic pelvic pain), one of the main endometriosis-related symptoms, up to 24 weeks after the first injection, demonstrated that cetrorelix use was associated with a highly statistically significant (p equals less than 0.001) improvement of pain score. Furthermore, therapeutic response associated with cetrorelix use was both rapid in onset (within four weeks) and durable, extending up to five months following cessation of cetrorelix administration. Importantly, clinical benefit seen with the use of cetrorelix was associated with only a slight and transient suppression of serum estrogen levels. Cetrorelix was well tolerated and was not associated with side effects, such as hormonal withdrawal symptoms seen during menopause.
The company believes that phase II data from this placebo-controlled trial, backed up by data from the two open-label, non-placebo controlled phase II trials, indicate that cetrorelix, unlike currently used treatments for endometriosis such as LHRH agonists, is suitable for long-term use as an intermittent treatment for endometriosis.
Endometriosis is the growth of the endometrium, or the inside lining of the uterus, outside of the uterus and is dependent upon the level of estrogen. Endometriosis affects approximately 10 per cent to 20 per cent of women of child-bearing age, and there is still a high medical need for new treatments. The total market size in 2003 was estimated to be around $800-million (U.S.).
Two placebo-controlled phase II trials were conducted to evaluate the efficacy of cetrorelix, including durability of therapeutic response associated with cetrorelix use during a four-month postinjection follow-up period, in 250 patients with BPH.
In the first phase II trial, patients with BPH received a single intramuscular injection of 30 milligrams (mg) or 60 mg of the same depot formulation of cetrorelix as that used in the placebo-controlled trial for endometriosis discussed above. In the second phase II trial, patients received four weekly subcutaneous injections of five mg or 10 mg of a different formulation of cetrorelix. In both studies, the clinical effects were followed for four months after the last injection.
As early as one month following initiation of therapy, data from both trials demonstrated a dose-dependent improvement of clinical symptoms, including IPSS (international prostate symptom score) and maximum uroflow in the cetrorelix treatment group in comparison with the placebo group. Importantly, the therapeutic response lasted three months following cessation of cetrorelix administration. In addition, the use of cetrorelix was associated with a slight reduction of prostate size. The clinical benefits seen with the use of cetrorelix were associated with a transient decrease of serum testosterone which never reached the castration level and thus did not have an adverse influence on sexual activity or libido.
Benign prostate hyperplasia is characterized by an abnormal, but not malignant, testosterone-mediated growth of prostate tissue. BPH is estimated to affect approximately 33 million men over 60 years of age. In 2004, the amount spent on drug treatment for this condition is expected to be around $1.8-billion (U.S.).
New preclinical data on perifosine in combination with radiotherapy
AEterna/Zentaris will also present new encouraging preclinical (in vivo) data on perifosine, the company's novel, first-in-class, oral AKT inhibitor in combination with radiation therapy.
Mouse xenograft tumour models were used to evaluate the anti-tumour activity of oral administration of perifosine or radiation alone as compared with perifosine in combination with radiation. Whereas the use of either treatment modality alone only delayed tumour growth, the combination regimen with both treatments led to complete tumour regression.
The company believes that these in vivo results support the continuing clinical development of perifosine in combination with radiotherapy as a potential treatment for multiple types of cancer. Phase I data on perifosine in combination with radiation therapy will be presented at the American Society of Clinical Oncology (ASCO) annual meeting in June, 2004.
AEterna/Zentaris plan to initiate phase II trials of perifosine in combination with radiotherapy, through the continuing collaboration with the Netherlands Cancer Institute of Amsterdam.
Advancement of teverelix in phase IIa trials
Earlier today, Ardana Bioscience, the worldwide partner of AEterna/Zentaris for the development and marketing of teverelix, a LHRH antagonist, has separately announced the initiation of a phase IIa trial for patients with prostate cancer, as well as the planned initiation of a new phase IIa trial in patients with BPH to be started later this week. The advancement of teverelix into phase IIa follows a recently completed phase I trial which helped establish the dosage regimens necessary to achieve different levels of testosterone suppression.
An audio webcast of the investor and analyst day presentations is available live and may be accessed by visiting the investors section of AEterna's website, www.aeterna.com. A replay will also be available at the same site.
WARNING: The company relies upon litigation protection for "forward-looking" statements