Welcome!

News Feed Item

New England Journal of Medicine Publishes Results From Phase 3 PREVAIL Trial of Enzalutamide in Men With Chemotherapy-Naive Metastatic Prostate Cancer Progressing Despite Androgen Deprivation Therapy

Study Appears in June 1 Online Edition

SAN FRANCISCO, CA and NORTHBROOK, IL -- (Marketwired) -- 06/01/14 -- Medivation, Inc. (NASDAQ: MDVN) and Astellas Pharma US, Inc., a U.S. subsidiary of Tokyo-based Astellas Pharma Inc. (TSE: 4503) today announced the online publication in the New England Journal of Medicine of the results from the Phase 3 PREVAIL trial, an international, randomized, double-blind, placebo-controlled clinical study of enzalutamide. The study evaluated the benefit and safety of enzalutamide in men with metastatic prostate cancer, who had few or no symptoms, that had progressed on luteinizing hormone-releasing hormone (LHRH) therapy or after bilateral orchiectomy. The paper, "Enzalutamide in Men with Metastatic Prostate Cancer Before Chemotherapy," appears in the June 1 online issue and the companies anticipate publication in a future print issue of the Journal.

"The PREVAIL study results demonstrate that treatment with enzalutamide in men with metastatic castration resistant prostate cancer can decrease the risk of death, delay the growth or spread of metastatic prostate cancer, and delay the time to initiation of chemotherapy," said Tomasz M. Beer, M.D., F.A.C.P., professor of medicine and deputy director of the Knight Cancer Institute at Oregon Health & Science University, and co-principal investigator of the PREVAIL study. "We are delighted that the New England Journal of Medicine has chosen to publish these important results."

A supplemental New Drug Application (sNDA) based on the PREVAIL results received a priority review designation from the U.S. Food and Drug Administration (FDA). The Prescription Drug User Fee Act (PDUFA) goal date is September 18, 2014. A variation application to amend the European Marketing Authorization Application based on the results of PREVAIL was validated for review by the European Medicines Agency on April 24, 2014.

About the PREVAIL Trial
The Phase 3 PREVAIL trial is a randomized, 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 Asia including Japan. The trial enrolled patients with chemotherapy-naïve metastatic prostate cancer whose disease progressed on androgen deprivation therapy (i.e., a luteinizing hormone-releasing hormone (LHRH) therapy or after bilateral orchiectomy). 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.

In the PREVAIL trial, men treated with enzalutamide demonstrated a statistically significant delay in cancer progression and reduction in the risk of death compared with placebo.

Enzalutamide reduced the risk of radiographic progression or death by 81% (HR=0.19; p < 0.0001), compared with placebo. The rate of radiographic progression-free survival at 12 months of follow up was 65% among patients treated with enzalutamide, as compared with 14% among patients receiving placebo.

Enzalutamide reduced the risk of death by 29% (HR=0.71; p < 0.0001), compared with placebo. A total of 626 patients (72%) in the enzalutamide group, as compared with 532 patients (63%) in the placebo group, were alive at the September 16, 2013 data cutoff date.

The most common clinically relevant adverse events associated with enzalutamide treatment as compared with placebo-treated patients in the PREVAIL trial included fatigue, hot flush and hypertension; 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. One patient experienced a seizure in each treatment group.

Enzalutamide Mechanism of Action
Enzalutamide is an androgen receptor inhibitor that acts on different steps in the androgen receptor signaling pathway. Enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors, and inhibit androgen receptor nuclear translocation and interaction with DNA.

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. In March 2014, Astellas and Medivation submitted a sNDA to the FDA seeking approval of XTANDI for the treatment of men with metastatic prostate cancer that has progressed on LHRH therapy or after bilateral orchiectomy. In May 2014, the FDA granted the sNDA application Priority Review designation with a PDUFA date of September 18, 2014.

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 randomized 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 randomized clinical trial were asthenia/fatigue, back pain, diarrhea, 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.

For Full Prescribing Information for XTANDI (enzalutamide) capsules, please visit www.XtandiHCP.com.

About Medivation
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 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 organization 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 www.astellas.com/en.

About the Astellas/Medivation Collaboration
In October 2009, Medivation and Astellas entered into a global agreement to jointly develop and commercialize enzalutamide. The companies are collaborating on a comprehensive development program that includes studies to develop enzalutamide across the full spectrum of advanced prostate cancer as well as advanced breast cancer. The companies jointly commercialize XTANDI in the United States and Astellas will have responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing XTANDI outside the United States.

Medivation Contact:
Mike Beyer
Sam Brown, Inc. (media for both companies)
(773) 463-4211

Astellas Contact:
Tyler Marciniak
Director, Communications and Advocacy
(847) 736-7145
Email Contact

More Stories By Marketwired .

Copyright © 2009 Marketwired. All rights reserved. All the news releases provided by Marketwired are copyrighted. Any forms of copying other than an individual user's personal reference without express written permission is prohibited. Further distribution of these materials is strictly forbidden, including but not limited to, posting, emailing, faxing, archiving in a public database, redistributing via a computer network or in a printed form.

Latest Stories
Internet of @ThingsExpo, taking place October 31 - November 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with the 21st International Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. @ThingsExpo Silicon Valley Call for Papers is now open.
Regardless of what business you’re in, it’s increasingly a software-driven business. Consumers’ rising expectations for connected digital and physical experiences are driving what some are calling the "Customer Experience Challenge.” In his session at @DevOpsSummit at 20th Cloud Expo, Marco Morales, Director of Global Solutions at CollabNet, will discuss how organizations are increasingly adopting a discipline of Value Stream Mapping to ensure that the software they are producing is poised to ...
DevOps is often described as a combination of technology and culture. Without both, DevOps isn't complete. However, applying the culture to outdated technology is a recipe for disaster; as response times grow and connections between teams are delayed by technology, the culture will die. A Nutanix Enterprise Cloud has many benefits that provide the needed base for a true DevOps paradigm. In his Day 3 Keynote at 20th Cloud Expo, Chris Brown, a Solutions Marketing Manager at Nutanix, will explore t...
When NSA's digital armory was leaked, it was only a matter of time before the code was morphed into a ransom seeking worm. This talk, designed for C-level attendees, demonstrates a Live Hack of a virtual environment to show the ease in which any average user can leverage these tools and infiltrate their network environment. This session will include an overview of the Shadbrokers NSA leak situation.
SYS-CON Events announced today that delaPlex will exhibit at SYS-CON's @ThingsExpo, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. delaPlex pioneered Software Development as a Service (SDaaS), which provides scalable resources to build, test, and deploy software. It’s a fast and more reliable way to develop a new product or expand your in-house team.
Interested in leveling up on your Cloud Foundry skills? Join IBM for Cloud Foundry Days on June 7 at Cloud Expo New York at the Javits Center in New York City. Cloud Foundry Days is a free half day educational conference and networking event. Come find out why Cloud Foundry is the industry's fastest-growing and most adopted cloud application platform.
In his opening keynote at 20th Cloud Expo, Michael Maximilien, Research Scientist, Architect, and Engineer at IBM, will motivate why realizing the full potential of the cloud and social data requires artificial intelligence. By mixing Cloud Foundry and the rich set of Watson services, IBM's Bluemix is the best cloud operating system for enterprises today, providing rapid development and deployment of applications that can take advantage of the rich catalog of Watson services to help drive insigh...
DevOps is often described as a combination of technology and culture. Without both, DevOps isn't complete. However, applying the culture to outdated technology is a recipe for disaster; as response times grow and connections between teams are delayed by technology, the culture will die. A Nutanix Enterprise Cloud has many benefits that provide the needed base for a true DevOps paradigm.
Automation is enabling enterprises to design, deploy, and manage more complex, hybrid cloud environments. Yet the people who manage these environments must be trained in and understanding these environments better than ever before. A new era of analytics and cognitive computing is adding intelligence, but also more complexity, to these cloud environments. How smart is your cloud? How smart should it be? In this power panel at 20th Cloud Expo, moderated by Conference Chair Roger Strukhoff, pane...
As enterprise cloud becomes the norm, businesses and government programs must address compounded regulatory compliance related to data privacy and information protection. The most recent, Controlled Unclassified Information and the EU’s GDPR have board level implications and companies still struggle with demonstrating due diligence. Developers and DevOps leaders, as part of the pre-planning process and the associated supply chain, could benefit from updating their code libraries and design by in...
The 21st International Cloud Expo has announced that its Call for Papers is open. Cloud Expo, to be held October 31 - November 2, 2017, at the Santa Clara Convention Center in Santa Clara, CA, brings together Cloud Computing, Big Data, Internet of Things, DevOps, Digital Transformation, Machine Learning and WebRTC to one location. With cloud computing driving a higher percentage of enterprise IT budgets every year, it becomes increasingly important to plant your flag in this fast-expanding busin...
Existing Big Data solutions are mainly focused on the discovery and analysis of data. The solutions are scalable and highly available but tedious when swapping in and swapping out occurs in disarray and thrashing takes place. The resolution for thrashing through machine learning algorithms and support nomenclature is through simple techniques. Organizations that have been collecting large customer data are increasingly seeing the need to use the data for swapping in and out and thrashing occurs ...
SYS-CON Events announced today that DivvyCloud will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. DivvyCloud software enables organizations to achieve their cloud computing goals by simplifying and automating security, compliance and cost optimization of public and private cloud infrastructure. Using DivvyCloud, customers can leverage programmatic Bots to identify and remediate common cloud problems in rea...
Most DevOps journeys involve several phases of maturity. Research shows that the inflection point where organizations begin to see maximum value is when they implement tight integration deploying their code to their infrastructure. Success at this level is the last barrier to at-will deployment. Storage, for instance, is more capable than where we read and write data. In his session at @DevOpsSummit at 20th Cloud Expo, Josh Atwell, a Developer Advocate for NetApp, will discuss the role and value...
SYS-CON Events announced today that Tintri, Inc, a leading provider of enterprise cloud infrastructure, will exhibit at SYS-CON's 20th International Cloud Expo®, which will take place on June 6-8, 2017, at the Javits Center in New York City, NY. Tintri offers an enterprise cloud platform built with public cloud-like web services and RESTful APIs. Organizations use Tintri all-flash storage with scale-out and automation as a foundation for their own clouds – to build agile development environments...