Prostate Centre-Discovered Cancer Drugs Show Promise

Two cancer drugs discovered at Vancouver Prostate Centre show promise in treating prostate and other cancers

During the recent American Society of Clinical Oncology (ASCO) annual meeting in Orlando, Florida, promising results from two drugs (OGX-011 and OGX-427) discovered at the Vancouver Prostate Centre were presented in two separate oral presentations, an unprecedented milestone for the Centre.

The Vancouver Prostate Centre is a UBC and CECR National Centre of Excellence whose integrated team-science approach and state of the art infrastructure facilitate rapid bench-to-bedside translation of discoveries. For example, discovery of clusterin and Hsp27 as proteins linked to therapeutic resistance and subsequent development and patenting of inhibitors (OGX-011, OGX-427) has led to 8 clinical trials in prostate, lung, and breast cancer across North America.

OGX-011 is an anti-cancer drug discovered and initially developed at the Vancouver Prostate Centre. The drug inhibits the production of a cell survival protein called clusterin that protects cancer cells. Clusterin is a heat shock "chaperone" protein, that helps cancer cells become resistant to treatments such as chemotherapy and radiation.

OGX-011was tested in a randomized Phase II multi-site National Cancer Institute of Canada trial and has shown considerable promise in the treatment of metastatic prostate cancer. The results were presented by Dr. Kim Chi, a medical oncologist with the BC Cancer Agency and principal investigator of the trial.

The trial enrolled 82 patients randomized to receive docetaxel plus prednisone alone or in combination with OGX-011. The median overall survival in patients treated in the OGX-011 arm was 23.8 months compared to 16.9 months for patients treated with docetaxel alone. Patients in the OGX-011 arm of the study had a death rate 39% lower than patients in the control arm. A prospectively defined multivariate analysis indicated that patients treated with OGX-011 had a rate of death 51% lower than patients treated with docetaxel alone (HR=0.49; p=0.012). These findings indicate Phase III trials are warranted.

In a separate presentation Dr Sebastien Hotte of the Juravinski Cancer Centre, Hamilton, Ontario presented data from a phase I dose finding trial of OGX 427 in patients with a variety of cancers. OGX-427 is designed to reduce production of Hsp27, a protein that is over-produced in response to many cancer treatments including hormone ablation therapy, chemotherapy and radiation therapy. Hsp27 production has been shown to inhibit cell death in tumor cells through a variety of mechanisms. Like OGX-011, this product candidate has potential as a treatment in a broad number of cancers.

OGX-427 was well tolerated as a monotherapy and demonstrated declines in circulating tumor cells at all doses evaluated as well as evidence of reduction in tumor markers. Reductions in circulating tumor cells and tumor markers both suggest single-agent activity warranting further clinical investigation.

“The advancement of OGX-427 into phase I clinical trials and OGX-011 into late stage clinical development are clear indicators of the Prostate Centre’s capacity to advance translational research from discovery to the clinic, and in making novel experimental therapies available to our patients,” says Dr Martin Gleave, director of the Prostate Centre, principal inventor of OGX-011 and OGX-427, and professor in the Department of Urologic Sciences at UBC. “The discovery and development of OGX-011 and OGX 427 illustrate our capacity to retain and add value to products spun out of our Centre which, in turn, supports Canadian biotech and economic growth in Canada.”

OGX-011 and OGX 427 have been out-licensed from UBC to OncoGenex Pharmaceuticals for commercial development and registration.

Click on the following links to view the Abstracts:

A Randomized Phase II Study of OGX-011 in Combination with Docetaxel and Prednisone or Docetaxel and Prednisone Alone in Patients with Metastatic Castration Resistant Prostate Cancer

A Phase 1 Study Evaluating a Second Generation Antisense Oligonucleotide (OGX-427) That Inhibits Heat Shock Protein 27 (Hsp27)