OncoGenex Pharmaceuticals Inc. today announced that it concluded a meeting with the U.S. Food and Drug Administration (FDA) on October 7, 2008, and that the FDA agreed that "durable pain palliation is an acceptable and desirable study endpoint" to support a product marketing approval for OGX-011 as a treatment for hormone refractory prostate cancer (HRPC).
In addition, OncoGenex reported that the FDA provided guidance on the submitted protocol including recommendations on study endpoints, the appropriate patient population, entry criteria and study conduct. The company plans to revise and submit the protocol for completing a Special Protocol Assessment with the FDA prior to initiating the registration trial.
Based on the results of this meeting, the Board of Directors of OncoGenex Pharmaceuticals has approved the release of 25% (347,207) of the shares held in escrow pursuant to agreements related to Sonus Pharmaceuticals' merger with OncoGenex Technologies described in its Proxy Statement filed with the SEC on July 3, 2008. The escrow agreements provided for the release of 25% of the shares held in escrow following the occurrence of a meeting with the FDA to confirm that pain palliation is an appropriate primary endpoint to support a product marketing approval in prostate cancer. A total of 694,431 milestone shares remain in escrow.
"Our data combining OGX-011 with second line chemotherapy in patients with HRPC has shown potential improvement in both pain palliation and survival. On July 14, 2008, OncoGenex announced that the company successfully completed an SPA with the FDA on the design of another Phase 3 registration trial of OGX-011 targeting overall survival as a primary endpoint for the treatment of HRPC," said Scott Cormack, President and CEO of OncoGenex Pharmaceuticals. "Obtaining FDA's agreement that pain palliation is an appropriate primary endpoint to support product approval in prostate cancer and receiving FDA's guidance on trial designs is essential to our plans to pursue development of OGX-011 using appropriate primary endpoints such as pain palliation and survival."
This planned registration trial to evaluate pain palliation is based on encouraging preliminary data from a Phase 2 study in HRPC indicating that OGX-011 treatment may result in durable pain palliation. These Phase 2 data were presented at the 2008 annual meeting of the American Society of Clinical Oncology (ASCO) and reported in a previous press release on June 2, 2008. In summary, the Phase 2 study included 42 patients with HRPC who had received first-line docetaxel therapy and required second-line chemotherapy. While follow up on surviving patients is still ongoing, preliminary findings related to pain palliation reported reductions in pain or analgesic use in approximately 50% of evaluable patients treated with either mitoxantrone plus OGX-011 or retreated with docetaxel plus OGX-011. These data are better than expected when compared to the 22-35% of patients receiving first-line chemotherapy who reported a reduction in pain in the primary Phase 3 study resulting in the approval of docetaxel (TAX 327 study) that was published in the October 7th, 2004 issue of the New England Journal of Medicine.
OGX-011, also known as custirsen sodium, is designed to block production of clusterin, a cell survival protein that is over-produced in several cancer indications and in response to many cancer treatments, including hormone ablation therapy, chemotherapy and radiation therapy. Increased clusterin production is observed in many human cancers, including prostate, non-small cell lung, breast, ovarian, bladder, renal, pancreatic, anaplastic large cell lymphoma and colon cancers and melanoma. Increased clusterin production is linked to faster rates of cancer progression, treatment resistance and shorter survival duration. OGX-011 is being evaluated in five Phase 2 clinical trials, each of which has completed patient enrollment. Interim study results have previously been presented for each of the five clinical trials.