Apr 7 2011
Teva Pharmaceutical Industries Ltd. (NASDAQ:TEVA) and OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) announced today that new preclinical data of their investigational compound custirsen (OGX-011/TV-1011) in castrate resistant prostate cancer (CRPC) were presented this week at the 102nd Annual Meeting of the AACR. These data provide additional evidence in support of the clinical potential of custirsen, a drug designed to block production of clusterin, that is currently being investigated in Phase III studies for CRPC.
Clusterin, a cell survival protein is over-produced in several cancer types and in response to many cancer treatments.
Study results show that clusterin regulates epithelial-mesenchymal transition (EMT) induced by the growth factor TGF beta and the transcription factor TWIST1 in prostate cancer cells. Both TGF beta and TWIST1 are known to be important regulators of EMT, the process in which cells undergo multiple biochemical changes that result in cancer cell migration, invasion and metastasis. These findings provide supporting evidence to the mechanism of clusterin expression and its relevance in the EMT of cancer cells.
"This study demonstrated that by inhibiting clusterin we can help reverse EMT, thereby identifying an important mechanism by which novel drugs like custirsen may inhibit cancer progression and improve patient outcomes," said Dr. Martin Gleave, Director of The Vancouver Prostate Centre at The University of British Columbia and study researcher. "These results establish clusterin inhibition as a valid therapeutic target, and underscore the importance of the ongoing Phase III trial program to demonstrate the clinical manifestation of the compound's mechanism of action."
Additionally, data were presented earlier this week that showed an inhibitory effect of custirsen on heat-shock protein 90 (HSP90) in prostate cancer cells. Inhibition of HSP90 is being investigated as a novel strategy for the treatment of prostate cancer, and the addition of custirsen may be able to enhance the activity of HSP90 inhibitors. Both abstracts can be found on the AACR website at http://www.aacr.org/.
These preclinical data further support the ongoing, Phase III custirsen development program in prostate cancer:
- The Prostate Cancer SATURN trial, evaluating a durable pain palliation benefit for custirsen in combination with docetaxel retreatment as second-line chemotherapy in approximately 300 patients with CRPC.
- The SYNERGY trial, evaluating a survival benefit for custirsen in combination with first-line docetaxel treatment in approximately 800 patients with CRPC.
Teva Pharmaceutical Industries Ltd.