OncoGenex Technologies Inc. Reports Lead Drug Candidate OGX-011 Achieved Primary Endpoint in Phase 2 Trial
VANCOUVER, Feb. 15 /PRNewswire/ - OncoGenex Technologies Inc. announced today that the Company's lead cancer drug candidate, OGX-011, also referred to as custirsen, was well-tolerated in combination with either docetaxel or mitoxantrone administered as second-line chemotherapy in patients with hormone refractory prostate cancer. Additionally, patients treated with second-line chemotherapy plus OGX-011 showed ongoing survival durations better than results published with chemotherapy alone. Phase 2 data were presented today at the 2008 Genitourinary Cancers Symposium. OncoGenex and Isis Pharmaceuticals, Inc. (Nasdaq: ISIS - News) are collaborating on development of OGX-011. According to data presented by Dr. Fred Saad, Professor of Surgery/Urology at the University of Montreal, the primary objectives of safety and tolerability were achieved in the 42 patients evaluated in the study. In addition, encouraging outcomes were observed with OGX-011 administered in combination with second-line chemotherapy.
- More chemotherapy than expected was safely administered to and tolerated by patients when OGX-011 was combined with second-line chemotherapy: Patients received a median of 6 cycles of mitoxantrone or 7.5 cycles of docetaxel as second-line chemotherapy. These data compare favorably with published reports documenting a median of 3-4 cycles with second-line chemotherapy alone.
- Survival was better than expected based on previously published reports: With a median follow-up of 13.3 months following second-line chemotherapy, approximately 30 percent of patients in both arms have not manifested disease progression and approximately 60 percent of patients remain alive in both arms. Median survival has not been reached in either arm. These data compare favorably with published results documenting median survivals of approximately 10 months.
- Reduction in pain or analgesic use was achieved in 50 percent or more of patients entering the study with pain: Reductions in pain or analgesic use were seen in 50 percent of evaluable patients treated with mitoxantrone and in 67 percent of evaluable patients retreated with docetaxel. These data compare favorably to the 22-35 percent of patients receiving first-line chemotherapy who reported reduction in pain in the TAX 327 study published in the New England Journal of Medicine on October 7, 2004.
This Phase 2 study was designed as an open-label, randomized, multicenter study evaluating weekly administration of OGX-011 in combination with second-line chemotherapy in patients with metastatic hormone refractory prostate cancer who were previously treated with a minimum of 2 cycles of docetaxel-based first-line chemotherapy. Patients in this study represented a poor prognostic population due to rapid disease progression after completing first-line docetaxel therapy with a median of 0.7 months in the mitoxantrone treated group or 2.1 months in the docetaxel retreated group. Because OGX-011 has been shown to enhance chemotherapy and reverse chemotherapy resistance in preclinical in vitro and in vivo models, the aim of this study was to assess the effect of OGX-011 in combination with either mitoxantrone or docetaxel retreatment as second-line chemotherapy. Phase 3 studies are planned utilizing chemotherapy plus OGX-011 as second-line therapy in patients progressing after a first-line docetaxel regimen.
"These data show that the combination of OGX-011 with docetaxel or mitoxantrone may improve treatment outcomes in second-line prostate cancer," said Dr. Fred Saad, who is also the primary investigator in the study. "The data also suggests that retreatment with docetaxel when combined with OGX-011 may reverse chemotherapy resistance in second-line docetaxel retreatment. We look forward to confirming these data in planned Phase 3 studies."
OGX-011 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. Clusterin levels may be further increased in response to standard cancer therapies, including hormone ablation therapy, chemotherapy and radiation therapy. Clusterin expression is linked to disease progression, treatment resistance, poor prognosis and survival in scientific publications. For example, increased expression of clusterin in prostate cancer is closely correlated with increasing Gleason score, which is a strong prognostic factor for poor survival of patients with prostate cancer.
OncoGenex is a private biopharmaceutical company committed to the development and commercialization of new cancer therapies that address treatment resistance in cancer patients. The company's three product candidates are designed to inhibit the production of specific proteins associated with treatment resistance and which are over-produced in response to a variety of cancer treatments. OGX-011 is completing evaluation in five Phase 2 clinical studies in prostate, lung, and breast cancers. OGX 427 has begun evaluation in Phase 1 clinical studies, while the third product candidate, OGX-225, has completed preclinical pharmacology studies. More information is available at www.oncogenex.ca.