OncoGenex Announces EMA Support for Phase 3 AFFINITY Trial Protocol AmendmentTopline results in poor prognosis subpopulation expected by end of year
BOTHELL, WA and VANCOUVER, British Columbia – Oct. 8, 2015 – OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) announced today that the European Medicines Agency (EMA) has completed its review of the proposed amendment to the company's Phase 3 AFFINITY protocol and statistical analysis plan. The amendment, which was agreed to by the U.S. Food and Drug Administration (FDA) earlier this year, includes the addition of a co-primary endpoint designed to prospectively evaluate the survival benefit of custirsen in men who are at increased risk for poor outcomes when treated with cabazitaxel for metastatic castrate-resistant prostate cancer (mCRPC). The EMA supported plans for prospectively defining a poor prognostic subpopulation in the Phase 3 AFFINITY trial and suggested additional supportive analyses to show benefit for the poor prognostic subpopulation beyond the broader AFFINITY trial population. Following support from the FDA and EMA, the company is proceeding with its planned protocol amendment globally.
"We are pleased that we now have feedback from both U.S. and European regulatory authorities on our plan to prospectively evaluate this group of mCRPC patients who have increased risk factors for poor outcomes and who therefore are more likely to have shorter survival times," said Cindy Jacobs, PhD, MD, Chief Medical Officer and Executive Vice President of OncoGenex. "As we continue to gather insights from the SYNERGY trial, we are gaining a better understanding of the role clusterin plays in this vulnerable patient group and how custirsen may provide a survival benefit."
OncoGenex, in collaboration with study investigators, has defined a simple five-criteria characterization for poor prognostic patients with prostate cancer to be treated with custirsen based on the Phase 3 SYNERGY trial, which includes: 1) poor performance status, 2) elevated prostate specific antigen (PSA), 3) elevated lactate dehyrdogenase (LDH), 4) decreased hemoglobin and 5) the presence of liver metastasis. AFFINITY patients with poor prognosis will be identified as having two or more of these five well-recognized high-risk criteria. The proposed change for AFFINITY is also consistent with custirsen's mechanism of action, as custirsen was designed to address treatment resistance which may be more prevalent in this subpopulation.
In the revised statistical analysis plan for the AFFINITY trial, the hypothesized hazard ratio (HR) for the poor prognosis subpopulation is specified to be 0.69 with the critical HR ≤ 0.778. The hypothesized HR for intent-to-treat patients (ITT population) remains unchanged as 0.75 with the critical HR ≤ 0.820.
Timing for the final analysis of the poor prognosis subpopulation is projected to occur by the end of 2015, while the final analysis of the ITT population is projected to occur in the second half of 2016. An interim analysis of the ITT population will coincide with the final analysis of the poor prognosis subpopulation. This interim analysis will have both futility and early efficacy criteria defined for the ITT population. If the final analysis of the poor prognostic subpopulation shows a survival benefit for custirsen, OncoGenex may initiate a regulatory submission.
A retrospective analysis of data from the Phase 3 SYNERGY trial presented earlier this year showed a benefit with custirsen therapy when added to first-line docetaxel chemotherapy in men with mCRPC who had a poor prognosis. The analysis showed that over 40 percent of men in the SYNERGY trial had at least two of the five common risk factors for poor prognosis as stated above. 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.
In addition, exploratory SYNERGY data analyses recently presented at the 2015 European Cancer Congress (ECC 2015) demonstrated that custirsen treatment significantly lowered serum clusterin (sCLU) levels from baseline in men with mCRPC. In addition, these data showed that sCLU reductions after custirsen treatment resulted in higher two-year survival rates in patients who were at increased risk for poor outcomes. Of those patients with lower sCLU levels, the data also showed a correlation to an overall survival benefit for custirsen-treated patients who were at increased risk for poor outcomes.
AFFINITY is being conducted at 95 global clinical trial sites. Earlier this year, the IDMC recommended the trial continue following the completion of an interim futility analysis. The trial is fully accrued and the protocol amendment does not affect the conduct of the study. Custirsen has Fast Track designation by the FDA for the poor prognosis and overall AFFINITY trial populations, as well as non-small cell lung cancer (NSCLC).
A major barrier to extending survival in patients with advanced cancer is treatment failure due to the ability of tumor cells to exploit fundamental cellular mechanisms that allow them to evade destruction by anti-cancer therapies. The production of the protein clusterin is a fundamental cellular repair mechanism that tumor cells exploit to evade destruction by anti-cancer therapies. Increased clusterin production has been linked to faster rates of cancer progression, treatment resistance and shorter survival duration in patients.
Custirsen is a highly specific clusterin inhibitor designed to improve survival in patients with advanced cancer by disabling a fundamental cellular repair mechanism used by tumor cells. Custirsen binds to clusterin mRNA to block the production of clusterin protein and has enhanced the tumor cell destructive effects of multiple anti-cancer therapies across a variety of tumor models. By inhibiting clusterin, custirsen is designed to alter tumor dynamics by slowing tumor growth and inhibiting tumor resistance to partner treatments, so that the benefits of therapy, including survival, may be extended.
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 expected timing for completion and results from our clinical trials and statements regarding the potential benefits and potential development of our product candidates. 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, 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 new developments in the rapidly evolving cancer therapy landscape require changes in our clinical trial plans or limit the potential benefits of our product 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.