OncoGenex's Phase 3 SYNERGY trial shows survival benefits of custirsen therapy in CRPC patients with poor prognosis

Jun 1 2015

OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) announced today that results from a retrospective analysis of the Phase 3 SYNERGY trial showed a benefit with custirsen therapy in men with metastatic castrate-resistant prostate cancer (CRPC) who had a poor prognosis. The analysis, exploring the effect of clusterin inhibition in men at risk for poor outcomes, showed that over 40 percent of men in the trial had at least two of five common risk factors for poor prognosis. In these men, the analysis found a 27 percent lower risk of death when custirsen was used in combination with first-line docetaxel compared to docetaxel alone. These results were presented at the 51st Annual Meeting of the American Society of Clinical Oncology in Chicago.

"Post-hoc analyses of the SYNERGY trial results provided an opportunity to explore where custirsen's optimal effect may be in patients with advanced prostate cancer, particularly those with risk factors for poor outcomes," said lead study investigator Kim Chi, M.D., Professor of Medicine at the Univeristy of British Columbia and Associate Director, Clinical Research, Vancouver Prostate Centre. "This analysis is encouraging because custirsen extended survival in a subset of patients who need new and innovative treatment options once their disease becomes resistant to initial treatments."

Custirsen is designed to block the production of the protein clusterin, which is overexpressed in a number of cancers and has been linked to faster rates of cancer progression, treatment resistance and shorter survival duration in patients. OncoGenex, in collaboration with study investigators, have defined a simple 5-criteria characterization for poor prognosis in prostate cancer based on the SYNERGY trial, which include: poor performance status, elevated prostate specific antigen (PSA), elevated lactate dehyrdogenase (LDH), decreased hemoglobin, and the presence of liver metastasis. The findings from the SYNERGY study show a preferential effect in patients who are more vulnerable to poor outcomes and may reveal the patient population most likely to benefit from clusterin inhibition in other studies.

"With these additional analysis from the SYNERGY trial, we believe we now have criteria for better assessing the patient population that is most likely to respond to custirsen," said Scott Cormack, President and CEO of OncoGenex. "These findings are particularly important because our ongoing AFFINITY and ENSPIRIT Phase 3 custirsen trials already include a higher percentage of patients who are at increased risk for poor outcomes. Evaluating survival specifically in these high-risk populations will be critical as we move forward with the custirsen development program."

The Company will be meeting with the U.S. Food and Drug Administration (FDA) in June to discuss a proposed amendment to the Phase 3 AFFINITY trial protocol and statistical analysis plan that would include a co-primary endpoint evaulating survival in men who are at increased risk for poor outcomes. In the AFFINITY trial, custirsen is being evaluated with second-line chemotherapy in men with metastatic CRPC. Results from this trial are expected later this year or in early 2016.

Custirsen is also being evaluated in the international Phase 3 ENSPIRIT trial of patients with non-small cell lung cancer (NSCLC) who have progressed following initial treatments. OncoGenex recently filed an amendment with the FDA and has initiated, or will be initiating, filings with regulatory agencies in other countries as it becomes the sponsor in those specific regions to amend the statistical design and analysis plan to more rigorously and expediently evaluate the potential survival benefit associated with custirsen in this aggressive disease. The second and final interim futility analysis will be conducted in mid-2015 and if passed, final survival results could be available as soon as the second half of 2016.

OncoGenex will be hosting a webcast on June 10, 2015 at 9:00 AM PT / 12:00 PM ET featuring Dr. Chi to discuss the results from the SYNERGY trial. The company will also provide an overview of data presented at ASCO from the Borealis-1 trial evaluating apatorsen in patients with metastatic bladder cancer.