OncoGenex Pharmaceuticals, Inc has reached an agreement with the US Food and Drug Administration (FDA) on the design of a second phase-3 registration trial of OGX-011, its lead product candidate targeting castrate resistant prostate cancer (CRPC), via the Special Protocol Assessment (SPA) process. The FDA has agreed that the design and planned analysis of our phase-3 trial featuring durable pain palliation as the primary endpoint adequately addresses the objectives necessary to support a regulatory submission.

"We have now received confirmations on two separate phase 3 trial designs from the FDA via the SPA process, each in second-line treatment of advanced prostate cancer," said Scott Cormack, president and CEO of OncoGenex Pharmaceuticals. "One trial design evaluates overall survival benefit while the second trial design evaluates reduction in pain as the primary endpoint. Having evaluated both of these endpoints in our phase-2 trials, we are well positioned to re-evaluate each of these endpoints in larger phase-3 registration trials."

"The FDA's acknowledgement of pain in addition to survival as key endpoints for market approval supports the basis of our OGX-011 development programme for advanced prostate cancer," added Cormack. "Although we observed a positive effect on PSA in our phase-2 trials of OGX-011, we recognize that PSA response has not been shown to correlate to a clinical benefit and therefore is not an acceptable endpoint for FDA approval. Our focus remains on survival and pain palliation, both endpoints that FDA has confirmed are appropriate for marketing approval, and both endpoints for which we have had success in our phase-2 clinical trials. Based on the recent survival benefit of combining OGX-011 with first-line docetaxel chemotherapy, we have initiated discussions with FDA for evaluating the overall survival benefit in first-line CRPC, instead of second-line CRPC."

The phase-3 trial evaluating durable pain palliation has been designed in collaboration with internationally recognized experts in the treatment of patients with CRPC (previously referred to as hormone-refractory prostate cancer) including Dr Tomasz Beer at the University of Oregon and Dr Sebastian Hotte at Juravinski Cancer Centre, in Hamilton, Ontario, Canada. This will be a randomized, controlled, international trial in approximately 300 men with metastatic CRPC who responded to first-line docetaxel therapy, but subsequently have progression of disease, including prostate cancer-related pain, and are able to receive docetaxel retreatment as second-line chemotherapy. Patients will be randomized to receive treatment with either OGX-011 and docetaxel/prednisone or docetaxel/prednisone alone. The primary endpoint of the trial will be to determine whether a greater proportion of patients in the arm treated with OGX-011 and docetaxel/prednisone experiences durable pain palliation as compared to patients in the arm treated with docetaxel/prednisone alone. It is expected that approximately 50 clinical sites in the United States and Canada will participate in this trial.

"Patients with pain due to metastatic prostate cancer generally require narcotic medications that are dosed to provide maximum pain relief; however, unacceptable side effects such as sedation and severe constipation remain dose-limiting. Because of this, patients frequently continue to suffer from pain despite 'optimally dosed' narcotics," said Cindy Jacobs, OncoGenex' executive vice-president and chief medical officer. "Thus, pain is a common, often unremitting and disabling symptom of advanced prostate cancer, and pain control is a key measurement of clinical benefit."

The planned initiation of this phase-3 trial evaluating pain palliation is supported by encouraging phase-2 data from patients receiving OGX-011 plus docetaxel as second-line chemotherapy - additional data was presented at the 2009 Annual Meeting of the American Urological Association (AUA). Based on the 27 patients who had prostate cancer-related pain and received OGX-011 plus docetaxel as second-line chemotherapy, 12 patients or 44 per cent of patients, experienced pain palliation for three months or longer. The majority of pain responses occurred within the first two cycles of OGX-011 plus docetaxel. These data compare favourably even when compared to pain responses observed after first-line chemotherapy. This is clinically relevant because patients receiving second-line treatment have more advanced disease and are thought to have more profound or resistant prostate cancer-related pain.

OGX-011 is designed to inhibit the production of clusterin, a protein that is associated with cancer treatment resistance and is currently being evaluated in phase-2 clinical trials in prostate, lung and breast cancer.

OncoGenex Pharma is a biopharmaceutical company committed to the development and commercialization of new therapies that address unmet needs in the treatment of cancer.