The September issue of the journals Clinical Cancer Research and Cancer Research published OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) announcement of new data from its Phase II clinical and a pre-clinical study of custirsen (OGX-011/TV-1011), a drug that inhibits the production of clusterin, which is a protein commonly over-produced in cancer cells and a cause of treatment failure.
OncoGenex is currently carrying out two Phase III studies evaluating custirsen in men with castrate-resistant prostate cancer (CRPC) and is currently enrolling CRPC patients. The trials consist of the ‘SYNERGY’ clinical trial, which will evaluate custirsen’s overall survival benefit in combination with first-line docetaxel treatment and the Prostate Cancer ‘SATURN’ Trial, which will evaluate a durable pain palliation benefit in patients receiving second-line chemotherapy.
The September 1, 2011 issue of Clinical Cancer Research published data from the Phase II clinical trial of custirsen in combination with docetaxel retreatment or mitoxantrone as second-line chemotherapy in patients with metastatic castrate-resistant prostate cancer (mCRPC).
According to the clinical study, overall survival was 15.8 months when custirsen was combined with docetaxel retreatment, in combination with mitoxantrone the overall survival was 11.5 months. The Phase II study also assessed mCRPC patients’ pain responses and discovered that the overall pain response was durable (greater than or equal to three months) in 88 percent of patients who suffered pain or were taking opioids for pain at study entry.
Dr. Fred Saad, Professor of Surgery/Urology at the University of Montreal and lead investigator on the study commented:
“These are encouraging results because we observed durable pain responses in many patients who had disease progression while on or shortly after first-line docetaxel treatment. These data suggest that custirsen may restore docetaxel sensitivity and potentially provide improvements in pain control for this difficult-to-treat patient population.”
The authors believe that further testing of custirsen combined with second-line chemotherapy in mCRPC is warranted based on the study’s results, as these demonstrate custirsen’s feasibility, safety and pain relief and link to low serum clusterin levels with longer survival.
The September 1, 2011 issue of Cancer Research published pre-clinical data demonstrating that clusterin inhibition using custirsen synergistically improves Heat-shock 90 (Hsp90) inhibitor activity by restraining the heat shock response in CRPC.
Heat-shock 90 (Hsp 90) inhibitors activate the elevation of compensatory survival mechanisms resulting in the production of clusterin. This leads to cancer cell survival and treatment resistance. Study results showed that when custirsen was combined with the Hsp90 inhibitor PF-04929113 or 17-AAG, the compounds worked synergistically to inhibit CPRC tumor cell growth in mice.
Dr. Martin Gleave, Director of The Vancouver Prostate Centre at The University of British Columbia and author of the study commented:
“These data support the broad, potential applicability of custirsen in combination with various anti-cancer treatments. This study is an example of how we continue to develop a greater understanding of cancer treatment resistance and identify opportunities to block these mechanisms in order to delay tumor progression.”
Custirsen has received Fast Track designation from the U.S. Food and Drug Administration (FDA) and is currently the only compound in development designed to inhibit clusterin production, a protein commonly over-produced in cancer cells, and one of the causes of treatment resistance. In contrast to opioids or agents that target the androgen receptor, custirsen is mechanistically unique in terms of its ability to impact pain responses via the regulation of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity, a potential attribute that could add to custirsen’s clinical benefit in combination with numerous anti-cancer treatments.
Written by Petra Rattue