2014年4月28日讯 /生物谷BIOON/ --仿制药巨头梯瓦（Teva Pharma）和OncoGenex制药4月28日公布了前列腺癌药物custirsen III期SYNERGY试验的数据。顶线生存数据表明，将custirsen添加至标准一线紫杉醇/泼尼松疗法，用于转移性去势性前列腺癌（CRPC）患者治疗时，未能显著改善总存活期（OS: 23.4个月 vs 22.2个月，p=0.207），未能达到研究的主要终点。该项研究中观察到的不良反应与custirsen已知的不良反应属性一致。相关疗效和安全性数据，将提交至即将召开的科学会议。
OncoGenex公司总裁兼CEO Scott Cormack称，SYNERGY研究的结果实属意想不到，尤其考虑到当前已有丰富的科学证据支持靶向凝聚素（clusterin）抗击一线前列腺癌的治疗抵抗。目前，该项研究数据的全面分析正在进行中，以便了解可能导致该项研究结果的潜在因素。
英文原文：OncoGenex, Teva say prostate cancer drug fails late-stage trial
BOTHELL, Wash. and VANCOUVER, British Columbia, April 28, 2014 /PRNewswire/ -- OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) today announced results from the Phase 3 SYNERGY trial. Top-line survival results indicate that the addition of custirsen to standard first-line docetaxel/prednisone therapy did not meet the primary endpoint of a statistically significant improvement in overall survival in men with metastatic castrate-resistant prostate cancer (CRPC), compared to docetaxel/prednisone alone (median survival 23.4 months vs 22.2 months, respectively; hazard ratio 0.93 and one-sided p value 0.207). The adverse events observed were similar to custirsen's known adverse event profile.
"The results of SYNERGY are unexpected, particularly given the wealth of scientific evidence supporting the targeting of clusterin to combat treatment resistance in first-line prostate cancer," said Scott Cormack, President and CEO of OncoGenex. "A thorough analysis of the data is underway to understand the potential factors that may have contributed to the results. Importantly, we remain strong in our belief that targeting mechanisms of treatment resistance is a critical path forward in the fight against cancer and we continue to actively pursue this approach through the two ongoing Phase 3 trials of custirsen and the seven Phase 2 trials of apatorsen in four tumor types. We would like to thank the men who participated in the SYNERGY trial and the friends and families who supported them."
OncoGenex will host a conference call and live webcast at 7:30 a.m. ET this morning.
To access the webcast, log on to the Investor Relations page of the OncoGenex website at www.oncogenex.com. Alternatively, you may access the live conference call 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.
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. 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.
As part of Phase 1 and Phase 2 clinical trials, custirsen was administered to 294 patients with various types of cancer. The majority of adverse events were mild. The most common adverse events associated with custirsen consisted of flu-like symptoms. The most common serious adverse events (SAE) associated with custirsen were febrile neutropenia, fever, pleural effusion, and dyspnea. Each SAE event was observed in approximately 2%-4% of patients.
The SYNERGY trial enrolled 1,022 men with mCRPC at more than 130 cancer centers throughout North America, Europe, Israel and South Korea. In the investigational arm of the trial, custirsen was administered as a weekly infusion of 640 mg following three loading doses, in combination with docetaxel and prednisone given as standard 3-week cycles. Patients in the active comparator arm received docetaxel and prednisone without custirsen. In both arms, patients were treated until disease progression, unacceptable toxicity, or completion of up to 10 cycles, unless additional cycles were deemed beneficial. Full efficacy and safety data from SYNERGY will be submitted for presentation at an upcoming scientific conference.
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. OncoGenex and Teva Pharmaceutical Industries Ltd. have entered a global collaboration and licensing agreement to develop and commercialize OncoGenex' lead drug candidate, custirsen. Custirsen utilizes second-generation antisense technology, licensed from Isis Pharmaceuticals (NASDAQ: ISIS), to effectively target and inhibit production of clusterin. OncoGenex and Isis partnered in the successful discovery of custirsen and in its initial 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.