QUEBEC CITY, Nov. 13 /PRNewswire-FirstCall/ - AEterna Zentaris Inc. today presented detailed positive Phase 2 results in hormone-dependent, inoperable prostate cancer for its luteinizing hormone-releasing hormone (LHRH) antagonist compound, ozarelix. Results were presented at the Societe Internationale d’Urologie (SIU) Meeting in Cape Town, South Africa by Professor Frans M.J. Debruyne from the Department of Urology, University Medical Center in Nijmegen, The Netherlands, and Chairman of the European Urology Association.
Data showed that the first primary efficacy endpoint of the study of finding a tolerable dosage regimen ensuring continuous suppression of testosterone at castration level (<0.5ng/ml) was achieved at a dose of 130 mg administered intramuscularly every four weeks during a three-month test period. The second primary efficacy endpoint relating to time for onset of action was also well achieved as the results showed that all patients had testosterone in castration range within two days after dosing. Furthermore, a secondary efficacy endpoint, related to a decrease in PSA level of at least 50 percent, was achieved with all patients. The Company reported top-line results from this study on August 2, 2006.
“These Phase 2 data provide further evidence that ozarelix, most importantly, is well tolerated and effective while demonstrating a unique very fast onset of action”, said Dr. Jurgen Engel, Executive Vice President, Global R&D and Chief Operating Officer at AEterna Zentaris. “We believe ozarelix has the potential to be beneficial in the treatment of additional hormone-dependent cancers and look forward to continuing its further clinical development.”
Ozarelix Phase 2 trial in hormone-dependent prostate cancer
The open-label, randomized-controlled, multi-center dose-finding Phase 2 trial with ozarelix was conducted with 64 patients suffering from hormone-dependent inoperable prostate cancer. The primary pharmacodynamic endpoint was continuous suppression of testosterone levels below 0.5 ng/mL between Day 8 and Day 85. Secondary endpoints included PSA response. The trial was conducted in Europe in collaboration with AEterna Zentaris’ partner Spectrum Pharmaceuticals Inc. .
Method
Three cohorts of 16 patients each were randomly assigned to the following Groups:
Group A: 100 mg (Day 1); Group B: 65 mg (Day 1 + Day 2); Group C: 65 mg (Day 1+ Day 8). One half of each cohort was randomized to re-treatment at the initial dose regimen, the other half was re-treated at 65 mg (Day 1 only) for the subsequent cycles.
A 16 patient extension of this initial study (Group D) tested the combination of Day 1 and Day 2 doses into a single day application of 130 mg. Repeat dosing every four weeks resulted in continuous suppression with all patients. Dosage regimen is shown on table below.
------------------------------------------------------------------------- Cycle 1 Cycle 2 and Cycle 3 Group --------------------- Group ---------------------- (n equals 16) Day 1 Day 2 Day 8 (n equals 8) Day 1 Day 2 Day 8 ------------------------------------------------------------------------- 1 A1 100 mg -- -- A 100 mg -- -- ---------------------------------- 2 A2 65 mg -- -- ------------------------------------------------------------------------- 3 B1 65 mg 65 mg -- B 65 mg 65 mg -- ---------------------------------- 4 B2 65 mg -- -- ------------------------------------------------------------------------- 5 C1 65 mg -- 65 mg C 65 mg -- 65 mg ---------------------------------- 6 C2 65 mg -- -- ------------------------------------------------------------------------- 7 D1 130 mg -- -- D 130 mg -- -- ---------------------------------- 8 D2 100 mg -- -- ------------------------------------------------------------------------- Results
The study achieved its primary endpoint of defining a tolerable dosage regimen of ozarelix that would ensure continuous suppression of testosterone at castration level (< 0.5 ng/ml) for a three-month test period. Dosage regimen B (65 mg on Day 1 and Day 2) provided the basis for the observation of continuous suppression and led to dosage regimen D of 130 mg per cycle where all patients remained suppressed to castration until at least day 85. At that dosage and in line with hormone-sensitive disease, serum PSA levels dropped in all patients upon testosterone withdrawal; PSA being the biological marker of tumor response.
The following are the details for the primary endpoint of the trial, the sustained suppression of testosterone into the castration range (group of 16 patients each):
- Group A: 100 mg single dose, repeated at 4 week intervals, allowed for escapes; - Group B: 65 mg on Day 1 and Day 2 given every 4 weeks was most efficient and consistently provided castration levels over the 3-month test period; - Group C: 65 mg on Day 1 and Day 8 every 4 weeks seemed slightly less efficient, possibly due to lower exposure by end of week 1; - Group D: 130 mg on Day 1 and 28. This extension of the initial study tested the combination of Day 1 and Day 2 into a single day application of 130 mg. Repeat dosing at 130 mg every 4 weeks resulted in continuous testosterone suppression for all patients.
From a safety perspective, ozarelix was well tolerated at all dosages. Hot flashes in 17 patients and sleep disorders in 3 patients were the predominant treatment emergent adverse events; all other events were observed in single patients only. There were no application-site reactions in any patient and just one episode of pruritus (severe itching), 2 months after start of treatment and considered unlikely related to ozarelix.
As previously announced, the Company, in collaboration with its partner Spectrum Pharmaceuticals, initiated an additional Phase 2b study which will enroll 32 patients at other European clinical sites with dose regimens delivering the four-week dose by single day delivery to verify and optimize the findings derived from the cohort of patients having received 130 mg of ozarelix per cycle.
Conclusion - Ozarelix at a dose of 130 mg suppresses testosterone to castration level over a period of 4 weeks; - 65 mg x 2 dosing on cycle Day 1 + 2 was more efficient than dosing on Day 1+8; - 130 mg dosing on cycle Day 1 only was equally efficient as 65 mg x 2 dosing on cycle Day 1+2; - Very rapid onset of testosterone suppression with castration was reached 2 days after application of 100 or 130 mg on day 1; - Re-dosing with 130 or 100 mg is efficient for long term testosterone suppression; - PSA response parallels testosterone suppression; - Ozarelix was well tolerated at 130 mg per cycle, given on Day 1 or as split doses of 65 mg each on separate days. About Ozarelix and Partnerships
Ozarelix is a fourth generation luteinizing hormone-releasing hormone (LHRH) antagonist administered as a depot formulation for the treatment of benign and malign hormone-dependent diseases. It is currently in advanced-stage clinical trials for benign prostatic hyperplasia and prostate cancer.
In August 2004, AEterna Zentaris granted Spectrum Pharmaceuticals an exclusive license to develop and market ozarelix for all potential indications in North America and India, while AEterna Zentaris retains exclusive rights to the rest of the world. Spectrum will also receive 50% of any upfront and milestone payments, royalties and/or profits from sales of the product in Japan.
Furthermore, AEterna Zentaris recently granted Japanese rights for all potential oncology indications to Nippon Kayaku, a key player in the Japanese oncology market.
About Prostate Cancer
According to Decision Resource, 395,000 new cases of prostate cancer were diagnosed in 2005 in the 7 major markets around the world. Treatment costs in these markets for this indication in 2005 were estimated at some US$3.3 billion.
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.
AETERNA ZENTARIS INC.
CONTACT: Media Relations, Paul Burroughs, (418) 652-8525 ext. 406,paul.burroughs@aeternazentaris.com; Investor Relations, Jenene Thomas,(418) 655-6420 or (908) 996-3154, jenene.thomas@aeternazentaris.com
