|By PR Newswire||
|January 28, 2014 05:02 PM EST||
SAN FRANCISCO and TOKYO, January 28, 2014 /PRNewswire/ --
--Study demonstrates statistically significant benefits in overall survival, radiographic progression-free survival, and a delay (17 months) in the time to initiation of chemotherapy--
Medivation Inc. (NASDAQ: MDVN) and Astellas Pharma Inc. (TSE: 4503) announced final results on the primary and secondary efficacy endpoints from the Phase 3 PREVAIL trial of enzalutamide in patients with chemotherapy-naïve metastatic prostate cancer who have failed androgen deprivation therapy and have few or no symptoms. Data will be shared in a late-breaking oral presentation at the upcoming American Society of Clinical Oncology (ASCO) 2014 Genitourinary (GU) Cancers Symposium in San Francisco on Thursday, January 30, 2014.[i]
"This is a significant step forward in prostate cancer therapy for men whose cancer has progressed, despite treatment with androgen deprivation therapy" said Professor Bertrand Tombal, MD, PhD, Chairman of the Division of the Urology, Cliniques Universitaires Saint Luc, Université Catholique de Louvain (UCL) and European Principal Investigator for PREVAIL. "As well as the clear efficacy benefits, what impressed me most about the results is that treatment with enzalutamide delays the time to initiation of chemotherapy, a key factor in maintaining quality of life in men with advanced prostate cancer."
The PREVAIL study results in men with metastatic prostate cancer who have progressed on androgen deprivation therapy are as follows:
- Treatment with enzalutamide demonstrated a statistically significant overall survival benefit compared with placebo treatment. Enzalutamide reduced the risk of death by 29% (HR=0.71; p<0.0001), compared with placebo. This benefit was observed despite substantial use of subsequent therapies (40% in the enzalutamide and 70% in the placebo groups).[i]
- Treatment with enzalutamide significantly reduced the risk of radiographic progression or death by 81% compared with placebo treatment (HR=0.19; p<0.0001). [i]
- Consistent benefits on these co-primary endpoints of overall survival and radiographic progression-free survival were observed across patient subgroups. [i]
- Men taking enzalutamide experienced a 17-month delay in the time to initiation of chemotherapy compared with men taking placebo (28.0 months versus 10.8 months; HR=0.35; p<0.0001).[i]
- The majority of men (58.8%) with soft tissue metastatic disease treated with enzalutamide versus 5% of patients treated with placebo had objective responses (complete responses or partial responses) including complete responses in 19.7% of enzalutamide patients compared with 1% of placebo patients. [i]
- Enzalutamide extended the median time to PSA progression from 2.8 months (placebo) to 11.2 months (HR=0.169; p<0.0001).[ii]
- Nearly 4 out of 5 patients in the enzalutamide group experienced a PSA decline of 50% or more, compared to less than 4% in the placebo group (78% vs. 3.5%; p<0.0001).[ii]
- The median times to deterioration in a measure of prostate cancer-specific quality of life, the Functional Assessment of Cancer Therapy-Prostate or FACT-P, were 11.3 months for the enzalutamide-treated patients and 5.6 months for the placebo patients (HR= 0.625, p<0.0001).[ii]
- The median treatment duration for enzalutamide was more than 3 times longer than for placebo (16.6 versus 4.6 months).[ii]
- Common side effects occurring during treatment and more common in the enzalutamide treated men included fatigue, back pain, constipation and arthralgia. Hypertension was observed in 13.4% of enzalutamide versus 4.1% of placebo-treated patients. Grade 3 or higher cardiac adverse events were reported in 2.8% of enzalutamide versus 2.1% of placebo-treated patients. Investigators reported zero seizures in the enzalutamide-treated group and one in the placebo group prior to the data cut-off date. One seizure was reported in the enzalutamide group after the data cut-off date. [i]
"Medivation's primary mission is to develop and make available to patients medically innovative therapies that provide clinically meaningful benefits and address major medical unmet needs among a spectrum of serious diseases," said David Hung, M.D., founder, president and CEO of Medivation. "Should enzalutamide be approved for use in this patient population, it will be a meaningful advance in the field of prostate cancer therapy."
"We are very excited about these results and the potential to offer a new treatment option for patients with metastatic castration resistant prostate cancer, in the pre-chemotherapy setting," said Dr Ayad Abdulahad, Senior Vice President, Medical Affairs Health Economics, APEL. "There remains a high unmet patient need for a new treatment that offers patients with advanced prostate cancer, not only the opportunity to live for longer, but to do so with a good quality of life. We are committed to work with our partners, Medivation, to seek the necessary European regulatory approval for this expanded use of enzalutamide, based on the results of PREVAIL."
Details of the presentation are as follows:
Title: Enzalutamide in men with chemotherapy-naïve metastatic prostate cancer (mCRPC): Results of Phase 3 PREVAIL Study
Presenter: Tomasz M. Beer, M.D., F.A.C.P., Knight Cancer Institute, Oregon Health & Science University
- Session Detail: Welcome and General Session 1: Integrating Androgen Axis Therapy across the Disease Spectrum
- Session Date/Time: January 30, 2014 from 7:45 a.m - 9:45 a.m.
About the PREVAIL Trial
The Phase 3 PREVAIL trial is a randomised, double-blind, placebo-controlled, multi-national trial that enrolled more than 1,700 patients at sites in the United States, Canada, Europe, Australia, Russia, Israel and Asian countries including Japan. The trial enrolled patients with metastatic prostate cancer whose disease progressed despite treatment with androgen deprivation therapy and had not yet received chemotherapy. The co-primary endpoints of the trial were overall survival and radiographic progression-free survival. The trial was designed to evaluate enzalutamide at a dose of 160 mg taken orally once daily versus placebo. Targeted enrollment was completed in May 2012 and the pre-specified interim analysis was conducted after 516 events (patient deaths).[iii]
Enzalutamide Mechanism of Action
XTANDI (enzalutamide) is a novel, oral, once-daily androgen receptor signalling inhibitor which works in three distinct ways: it inhibits testosterone binding to androgen receptors, nuclear translocation of androgen receptors; and DNA binding and activation by androgen receptors.[iv]
About XTANDI® (enzalutamide) capsules
XTANDI was approved by the FDA on August 31, 2012 and is indicated for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously received docetaxel.
Enzalutamide is currently licensed in Europe for the treatment of adult men with metastatic castration-resistant prostate cancer whose disease has progressed on or after docetaxel therapy.[iv]
Important Safety Information for XTANDI (from the approved prescribing information)
Contraindications- XTANDI can cause fetal harm when administered to a pregnant woman based on its mechanism of action. XTANDI is not indicated for use in women. XTANDI is contraindicated in women who are or may become pregnant.
Warnings and Precautions- In the randomised clinical trial, seizure occurred in 0.9% of patients on XTANDI. No patients on the placebo arm experienced seizure. Patients experiencing a seizure were permanently discontinued from therapy. All seizures resolved. Patients with a history of seizure, taking medications known to decrease the seizure threshold, or with other risk factors for seizure were excluded from the clinical trial. Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others.
Adverse Reactions- The most common adverse drug reactions (≥ 5%) reported in patients receiving XTANDI in the randomised clinical trial were asthenia/fatigue, back pain, diarrhoea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension.
Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and in 6% on placebo (no Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients and 2% on placebo. One percent of XTANDI patients compared to 0.3% on placebo died from infections or sepsis. Falls or injuries related to falls occurred in 4.6% of XTANDI patients versus 1.3% on placebo. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients and included non-pathologic fractures, joint injuries, and hematomas. Grade 1 or 2 hallucinations occurred in 1.6% of XTANDI patients and 0.3% on placebo, with the majority on opioid-containing medications at the time of the event.
Drug Interactions- Effect of Other Drugs on XTANDI: Administration of strong CYP2C8 inhibitors can increase the plasma exposure to XTANDI. Co-administration of XTANDI with strong CYP2C8 inhibitors should be avoided if possible. If co-administration of XTANDI cannot be avoided, reduce the dose of XTANDI. Co-administration of XTANDI with strong or moderate CYP3A4 and CYP2C8 inducers can alter the plasma exposure of XTANDI and should be avoided if possible.
Effect of XTANDI on Other Drugs: XTANDI is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. Avoid CYP3A4, CYP2C9 and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring.
Medivation, Inc. is a biopharmaceutical company focused on the rapid development of novel small molecule drugs to treat serious diseases for which there are limited treatment options. Medivation aims to transform the treatment of these diseases and offer hope to critically ill patients and their families. For more information, please visit us at http://www.medivation.com.
About Astellas Pharma Inc.
Astellas Pharma Inc. is a pharmaceutical company dedicated to improving the health of people around the world through provision of innovative and reliable pharmaceuticals. The organisation is committed to being a global category leader in Oncology and Urology, and has several oncology compounds in development in addition to enzalutamide. For more information on Astellas Pharma Inc., please visit our website at http://www.astellas.com/en.
i. Beer T, et al. Enzalutamide Decreases Risk of Death and Delays Progression in Phase 3 Trial of Men with Metastatic Prostate Cancer. Presentation ASCO GU 2014
ii. Phung, et al. PREVAIL results, APGD Leadership Team Presentation
iii. http://clinicaltrials.gov/ct2/show/NCT01212991. Last accessed January 2014
iv. European Medicines Agency, XTANDI, (enzalutamide) Summary of Product Characteristics, 2013
Chief Business & Financial Officer
Senior Director, Investor Relations
Red Door Communications
The cloud competition for database hosts is fierce. How do you evaluate a cloud provider for your database platform? In his session at 18th Cloud Expo, Chris Presley, a Solutions Architect at Pythian, will give users a checklist of considerations when choosing a provider. Chris Presley is a Solutions Architect at Pythian. He loves order – making him a premier Microsoft SQL Server expert. Not only has he programmed and administered SQL Server, but he has also shared his expertise and passion w...
Feb. 13, 2016 10:30 AM EST
Join us at Cloud Expo | @ThingsExpo 2016 – June 7-9 at the Javits Center in New York City and November 1-3 at the Santa Clara Convention Center in Santa Clara, CA – and deliver your unique message in a way that is striking and unforgettable by taking advantage of SYS-CON's unmatched high-impact, result-driven event / media packages.
Feb. 13, 2016 10:00 AM EST
As enterprises work to take advantage of Big Data technologies, they frequently become distracted by product-level decisions. In most new Big Data builds this approach is completely counter-productive: it presupposes tools that may not be a fit for development teams, forces IT to take on the burden of evaluating and maintaining unfamiliar technology, and represents a major up-front expense. In his session at @BigDataExpo at @ThingsExpo, Andrew Warfield, CTO and Co-Founder of Coho Data, will dis...
Feb. 13, 2016 09:45 AM EST Reads: 228
The Art of DevOps provides a fun overview to help teams understand DevOps. Written in the style of the famous 6th century Chinese manuscript “The Art of War,” this eBook describes DevOps in the form of a mission to continuously deliver assets to the operational battlegrounds safely, securely, and quickly. It’s a fun read with valuable insights.
Feb. 13, 2016 09:30 AM EST
SYS-CON Events announced today that (ISC)²® (“ISC-squared”) will exhibit at SYS-CON's 18th International Cloud Expo®, which will take place on June 7-9, 2016, at the Javits Center in New York City, NY. Two leading non-profits focused on cloud and information security, (ISC)² and Cloud Security Alliance (CSA), developed the Certified Cloud Security Professional (CCSP) certification to address the increased demand for cloud security expertise due to rapid growth in cloud. Recently named “The Next...
Feb. 13, 2016 09:30 AM EST
Advances in technology and ubiquitous connectivity have made the utilization of a dispersed workforce more common. Whether that remote team is located across the street or country, management styles/ approaches will have to be adjusted to accommodate this new dynamic. In his session at 17th Cloud Expo, Sagi Brody, Chief Technology Officer at Webair Internet Development Inc., focused on the challenges of managing remote teams, providing real-world examples that demonstrate what works and what do...
Feb. 13, 2016 09:00 AM EST Reads: 342
As someone who has been dedicated to automation and Application Release Automation (ARA) technology for almost six years now, one of the most common questions I get asked regards Platform-as-a-Service (PaaS). Specifically, people want to know whether release automation is still needed when a PaaS is in place, and why. Isn't that what a PaaS provides? A solution to the deployment and runtime challenges of an application? Why would anyone using a PaaS then need an automation engine with workflow ...
Feb. 13, 2016 09:00 AM EST Reads: 246
Recognizing the need to identify and validate information security professionals’ competency in securing cloud services, the two leading membership organizations focused on cloud and information security, the Cloud Security Alliance (CSA) and (ISC)^2, joined together to develop an international cloud security credential that reflects the most current and comprehensive best practices for securing and optimizing cloud computing environments.
Feb. 13, 2016 08:00 AM EST
DevOps is not just last year’s buzzword. Companies with DevOps practices are 2.5x more likely to exceed profitability, market share, and productivity goals. But how do you enable high performance? What can you do right now to start? Find out from DevOps experts including Gene Kim, co-author of "The Phoenix Project," and the Dynatrace Center of Excellence.
Feb. 13, 2016 07:30 AM EST
Predictive analytics tools monitor, report, and troubleshoot in order to make proactive decisions about the health, performance, and utilization of storage. Most enterprises combine cloud and on-premise storage, resulting in blended environments of physical, virtual, cloud, and other platforms, which justifies more sophisticated storage analytics. In his session at 18th Cloud Expo, Peter McCallum, Vice President of Datacenter Solutions at FalconStor, will discuss using predictive analytics to ...
Feb. 13, 2016 06:45 AM EST Reads: 420
Silver Spring Networks, Inc. (NYSE: SSNI) extended its Internet of Things technology platform with performance enhancements to Gen5 – its fifth generation critical infrastructure networking platform. Already delivering nearly 23 million devices on five continents as one of the leading networking providers in the market, Silver Spring announced it is doubling the maximum speed of its Gen5 network to up to 2.4 Mbps, increasing computational performance by 10x, supporting simultaneous mesh communic...
Feb. 13, 2016 05:00 AM EST
Eighty percent of a data scientist’s time is spent gathering and cleaning up data, and 80% of all data is unstructured and almost never analyzed. Cognitive computing, in combination with Big Data, is changing the equation by creating data reservoirs and using natural language processing to enable analysis of unstructured data sources. This is impacting every aspect of the analytics profession from how data is mined (and by whom) to how it is delivered. This is not some futuristic vision: it's ha...
Feb. 13, 2016 04:45 AM EST Reads: 469
The cloud promises new levels of agility and cost-savings for Big Data, data warehousing and analytics. But it’s challenging to understand all the options – from IaaS and PaaS to newer services like HaaS (Hadoop as a Service) and BDaaS (Big Data as a Service). In her session at @BigDataExpo at @ThingsExpo, Hannah Smalltree, a director at Cazena, will provide an educational overview of emerging “as-a-service” options for Big Data in the cloud. This is critical background for IT and data profes...
Feb. 13, 2016 03:45 AM EST Reads: 248
Father business cycles and digital consumers are forcing enterprises to respond faster to customer needs and competitive demands. Successful integration of DevOps and Agile development will be key for business success in today’s digital economy. In his session at DevOps Summit, Pradeep Prabhu, Co-Founder & CEO of Cloudmunch, covered the critical practices that enterprises should consider to seamlessly integrate Agile and DevOps processes, barriers to implementing this in the enterprise, and pr...
Feb. 13, 2016 03:00 AM EST Reads: 470
The principles behind DevOps are not new - for decades people have been automating system administration and decreasing the time to deploy apps and perform other management tasks. However, only recently did we see the tools and the will necessary to share the benefits and power of automation with a wider circle of people. In his session at DevOps Summit, Bernard Sanders, Chief Technology Officer at CloudBolt Software, explored the latest tools including Puppet, Chef, Docker, and CMPs needed to...
Feb. 13, 2016 02:30 AM EST Reads: 371