OncoGenex Announces Data from the Phase 3 SYNERGY Trial Showing a Survival Benefit with Custirsen in Patients with Poor Prognosis

Significant reduction in risk of death observed in those patients with most common risk factors that drive poor outcomes in prostate cancer

Discussions with regulatory agencies underway to include co-primary endpoint evaluating the effect of custirsen in patients with poor prognosis in ongoing Phase 3 AFFINITY trial

May 30, 2015, 14:15 ET from OncoGenex Pharmaceuticals, Inc.

BOTHELL, Wash. and VANCOUVER, British Columbia, May 30, 2015 /PRNewswire/ -- 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. Access to this live event will be available on the Investor Relations section of the OncoGenex website at www.OncoGenex.com. Alternatively, the event may be accessed by dialing (877) 606-1416 (U.S. & Canada) or (707) 287-9313 (International). A webcast replay will be available approximately two hours after the call and will be archived on www.OncoGenex.com for 90 days.

About the SYNERGY Trial The SYNERGY trial evaluated custirsen plus docetaxel/prednisone compared with docetaxel/prednisone alone in men with metastatic CRPC (n=1,022).  Following 509 deaths, median overall survival (OS) was 23.4 months (m) vs. 22.2 m for custirsen and control arms, respectively (hazard ratio [HR] 0.93; P = 0.42).  

In retrospective analyses, a prognostic scoring system was developed in the control arm using multiple variable modeling and was used to dichotomize patients into good and poor prognosis.  The analysis included 984 patients with complete data. Median survival for the poor and good prognosis groups in the control arm was 14.0 m and 30.4 m, respectively (HR = 3.66).

The custirsen HR effect differed between poor and good prognosis groups (interaction P = 0.069). The HR estimate for custirsen survival benefit for those in the poor prognosis group was 0.73 (95% CI: 0.59 to 0.90) and 1.02 (95% CI: 0.76 to 1.37) for those in the good prognosis. When analyzed separately (n=492), the median OS in the poor prognostic group was 17.0 m in the custirsen arm vs. 14.0 m in the control arm (HR=0.73, 95%CI: 0.59 to 0.90, P = 0.004).

A more simplified prognostic index score showed that over 40% of men in the trial had at least two of five common risk factors for poor prognosis.  In these men, the analysis also showed a 27% lower risk of death when custirsen was used in combination with first-line docetaxel compared to docetaxel alone. 

The adverse events (AEs) observed in the SYNERGY trial were similar to custirsen's known AE  profile.   The most common  serious AEs observed in 2 percent of patients treated with custirsen, beyond those observed in the control arm, included febrile neutropenia, pneumonia and fever. The most common grade 3 or higher adverse events in 3 percent of patients, whether classified as good or poor prognosis patients, were neutropenia, anemia, fatigue and febrile neutropenia.

About Custirsen Custirsen is an experimental drug that is designed to block the production of the protein clusterin, which may play a fundamental role in cancer cell survival and treatment resistance. Clusterin is upregulated in tumor cells in response to treatment interventions such as chemotherapy, hormone ablation and radiation therapy and has been found to be overexpressed in a number of cancers, including prostate, lung, breast and bladder. Increased clusterin production has been linked to faster rates of cancer progression, treatment resistance and shorter survival duration in patients. By inhibiting clusterin, custirsen is designed to alter tumor dynamics, slowing tumor growth and resistance to partner treatments, so that the benefits of therapy, including survival, may be extended.

Custirsen has Fast Track designation by the FDA for NSCLC and metastatic CRPC.

About OncoGenex OncoGenex is a biopharmaceutical company committed to the development and commercialization of new therapies that address treatment resistance in cancer patients. OncoGenex has a diverse oncology pipeline, with each product candidate having a distinct mechanism of action and representing a unique opportunity for cancer drug development. Custirsen is currently in Phase 3 clinical development as a treatment in men with metastatic castrate-resistant prostate cancer and in patients with advanced, unresectable non-small cell lung cancer. Apatorsen is in Phase 2 clinical development and OGX-225 is currently in pre-clinical development. More information is available at www.OncoGenex.com and at the company's Twitter account:  https://twitter.com/OncoGenex_IR.

OncoGenex' Forward Looking Statements This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the potential benefits and potential development of our product candidates and statements regarding our clinical trial plans and timelines. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements. Such forward-looking statements are subject to risks and uncertainties, including, among others, the risk that our product candidates do not demonstrate the hypothesized or expected benefits, the risk of delays in our expected clinical trials, the risk that the FDA does not approve our proposed amendments to our clinical trials, the risk that new developments in the rapidly evolving cancer therapy landscape require changes in our clinical trial plans or limit the potential benefits of our product, the risk that our cash resources are insufficient to fund our planned activities for the time period expected and the other factors described in our risk factors set forth in our filings with the Securities and Exchange Commission from time to time, including the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q. The Company undertakes no obligation to update the forward-looking statements contained herein or to reflect events or circumstances occurring after the date hereof, other than as may be required by applicable law.


SOURCE OncoGenex Pharmaceuticals, Inc.