AEterna Zentaris Inc. has reported it has reached its goal of recruiting 500 patients for the safety study of the Phase 3 program in benign prostatic hyperplasia (BPH) with its flagship product candidate, cetrorelix, a novel investigational luteinizing hormone-releasing hormone (LHRH) antagonist.
This safety trial, the third of three Phase 3 studies - involving a total of over 1,500 patients -will define the role of cetrorelix in the treatment of BPH, a non-cancerous enlargement of the prostate affecting millions of men.
"With today's announcement, all three trials of our Phase 3 program in BPH with cetrorelix are now fully recruited according to our scheduled timelines. We now look forward to the disclosure of the first efficacy results in the third quarter of 2009 which could be followed by an NDA in 2010," said Paul Blake, M.D., Senior Vice President and Chief Medical Officer at AEterna Zentaris. "Furthermore, this milestone brings us one step closer to our goal of providing a novel, safe and efficient therapeutic approach to the millions of men suffering from BPH."
The safety study titled, "Cetrorelix pamoate in patients with symptomatic BPH: an open-labeled safety and efficacy assessment study", being conducted in North America, will assess an intermittent dosage regimen of cetrorelix pamoate as a potential safe and tolerable treatment providing prolonged improvement in BPH-related signs and symptoms. Patients receive cetrorelix pamoate by intra-muscular (IM) injection at Weeks 0 and 2, and are followed up to Week 26. The main endpoint is the incidence of possibly drug-related adverse events.
Cetrorelix is part of AEterna Zentaris' LHRH antagonist therapeutic approach that has demonstrated in Phase 2 studies to provide fast and long-lasting relief of BPH symptoms while being well tolerated, with a low incidence of sexual side effects. Cetrorelix peptide-based drugs were developed by the Company in cooperation with Nobel Prize winner Prof. Andrew Schally, currently of the U.S. Veterans Administration in Miami.
Cetrorelix acetate is marketed under the brand name Cetrotide(R), the first LHRH antagonist approved for therapeutic use as part of in vitro fertilization programs (controlled ovarian stimulation/assisted reproductive technologies) in Europe, the U.S. and Japan. It was launched on the market through Serono (now Merck Serono) in the United States, Europe and in several other countries, as well as in Japan through Shionogi.
Cetrorelix pamoate is being studied in three Phase 3 trials which include over 1,500 men with symptomatic BPH in the United States, Canada and Europe. The first Phase 3 efficacy trial conducted primarily in the United States and Canada and with additional sites in Europe, involves approximately 600 patients (completion of patient recruitment announced on April 15, 2008) and is being led by Herbert Lepor, M.D., Professor and Martin Spatz Chairman of Urology, New York University School of Medicine, New York. In the trial, patients enter a no-treatment run-in observation period to confirm severity and stability of voiding symptoms based on the International Prostate Symptom Score (I-PSS). Patients are then randomly allocated to cetrorelix or placebo in a double-blind fashion. Patients are administered cetrorelix by intra-muscular (IM) injection at Week 0, 2, 26 and 28 and are followed up to Week 52. Then, in an open-label extension, patients will receive cetrorelix by IM injection at Week 52, 54, 78 and 80 and will be followed up to Week 90.
A second, similarly designed ongoing multi-center Phase 3 efficacy study (completion of patient recruitment announced on October 1, 2008), led by Prof. Frans M.J. Debruyne, M.D., Ph.D., from The Netherlands, involves approximately 400 patients, mainly in Europe.
The third Phase 3 trial (completion of patient recruitment was announced today) is an open-label, single-armed multi-center safety study involving approximately 500 patients in North America, and is being led by Joel Kaufman, M.D., Associate Clinical Professor of Urology, University of Colorado School of Medicine, Denver, Colorado, and Urology Research Options, Aurora, Colorado.
The primary endpoint for both North American and European efficacy studies is the change in I-PSS between baseline and Week 52. Other efficacy endpoints include additional measures of BPH-symptom progression and the need for BPH-related surgery. Safety endpoints include changes in sexual function. Other important endpoints include plasma changes in levels of testosterone, and assessment of other adverse events.
The cetrorelix Phase 3 program is based on comprehensive clinical practice guidelines to ensure quality control, including input from expert advisors on study design, publishing results in peer-reviewed journals and discussion of the studies with regulatory agencies.