|By Marketwired .||
|June 1, 2014 09:01 AM EDT||
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.
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.
Sam Brown, Inc. (media for both companies)
Director, Communications and Advocacy
"ElasticBox is an enterprise company that makes it very easy for developers and IT ops to collaborate to develop, build and deploy applications on any cloud - private, public or hybrid," stated Monish Sharma, VP of Customer Success at ElasticBox, in this SYS-CON.tv interview at DevOps Summit, held Nov 4–6, 2014, at the Santa Clara Convention Center in Santa Clara, CA.
Jan. 28, 2015 11:00 PM EST Reads: 2,568
The Internet of Things (IoT) promises to evolve the way the world does business; however, understanding how to apply it to your company can be a mystery. Most people struggle with understanding the potential business uses or tend to get caught up in the technology, resulting in solutions that fail to meet even minimum business goals. In his session at @ThingsExpo, Jesse Shiah, CEO / President / Co-Founder of AgilePoint Inc., showed what is needed to leverage the IoT to transform your business. ...
Jan. 28, 2015 07:30 PM EST Reads: 3,239
IoT is still a vague buzzword for many people. In his session at @ThingsExpo, Mike Kavis, Vice President & Principal Cloud Architect at Cloud Technology Partners, discussed the business value of IoT that goes far beyond the general public's perception that IoT is all about wearables and home consumer services. He also discussed how IoT is perceived by investors and how venture capitalist access this space. Other topics discussed were barriers to success, what is new, what is old, and what th...
Jan. 28, 2015 06:15 PM EST Reads: 4,033
Dale Kim is the Director of Industry Solutions at MapR. His background includes a variety of technical and management roles at information technology companies. While his experience includes work with relational databases, much of his career pertains to non-relational data in the areas of search, content management, and NoSQL, and includes senior roles in technical marketing, sales engineering, and support engineering. Dale holds an MBA from Santa Clara University, and a BA in Computer Science f...
Jan. 28, 2015 06:00 PM EST Reads: 3,205
The Internet of Things (IoT) is rapidly in the process of breaking from its heretofore relatively obscure enterprise applications (such as plant floor control and supply chain management) and going mainstream into the consumer space. More and more creative folks are interconnecting everyday products such as household items, mobile devices, appliances and cars, and unleashing new and imaginative scenarios. We are seeing a lot of excitement around applications in home automation, personal fitness,...
Jan. 28, 2015 06:00 PM EST Reads: 2,957
“The year of the cloud – we have no idea when it's really happening but we think it's happening now. For those technology providers like Zentera that are helping enterprises move to the cloud - it's been fun to watch," noted Mike Loftus, VP Product Management and Marketing at Zentera Systems, in this SYS-CON.tv interview at Cloud Expo, held Nov 4–6, 2014, at the Santa Clara Convention Center in Santa Clara, CA.
Jan. 28, 2015 05:00 PM EST Reads: 2,126
The Industrial Internet revolution is now underway, enabled by connected machines and billions of devices that communicate and collaborate. The massive amounts of Big Data requiring real-time analysis is flooding legacy IT systems and giving way to cloud environments that can handle the unpredictable workloads. Yet many barriers remain until we can fully realize the opportunities and benefits from the convergence of machines and devices with Big Data and the cloud, including interoperability, ...
Jan. 28, 2015 04:00 PM EST Reads: 2,715
OneCloud Software has launched the OneCloud Partner Program. Responding to demand from prospective partners, the Program offers managed service providers (MSPs) and resellers the resources they need to grow their business with the OneCloud Recovery solution. OneCloud Recovery is an automated solution for disaster recovery/business continuity (DR/BC), which leverages Amazon Web Services as the disaster recovery site. “This is a tremendous opportunity with an innovative hybrid cloud-based DR pro...
Jan. 28, 2015 03:30 PM EST Reads: 875
Cloud Technology Partners on Wednesday announced it has been recognized by the Modern Infrastructure Impact Awards as one of the Best Amazon Web Services (AWS) Consulting Partners. Selected by the editors of TechTarget's SearchDataCenter.com, and by votes from customers and strategic channel partners, the companies acknowledged by the Modern Infrastructure Impact Awards represent the top providers of cloud consulting services for AWS including application migration, application development, inf...
Jan. 28, 2015 03:00 PM EST Reads: 1,438
MapR Technologies on Tuesday announced the availability of free Hadoop On-Demand Training for developers, analysts and administrators which represents a $50M in-kind contribution* to the broad Hadoop community. The Hadoop training program is a multi-course curriculum designed to expand worldwide adoption of Hadoop technology. The curriculum provides engaging and interactive video lessons, hands-on exercises, labs and quizzes, enabling professionals to acquire valuable Hadoop skills and knowledge...
Jan. 28, 2015 03:00 PM EST Reads: 718
“We help people build clusters, in the classical sense of the cluster. We help people put a full stack on top of every single one of those machines. We do the full bare metal install," explained Greg Bruno, Vice President of Engineering and co-founder of StackIQ, in this SYS-CON.tv interview at 15th Cloud Expo, held Nov 4–6, 2014, at the Santa Clara Convention Center in Santa Clara, CA.
Jan. 28, 2015 02:45 PM EST Reads: 2,423
"Blue Box has been around for 10-11 years, and last year we launched Blue Box Cloud. We like the term 'Private Cloud as a Service' because we think that embodies what we are launching as a product - it's a managed hosted private cloud," explained Giles Frith, Vice President of Customer Operations at Blue Box, in this SYS-CON.tv interview at DevOps Summit, held Nov 4–6, 2014, at the Santa Clara Convention Center in Santa Clara, CA.
Jan. 28, 2015 02:30 PM EST Reads: 2,597
In this demo at 15th Cloud Expo, John Meza, Product Engineer at Esri, showed how Esri products hook into Hadoop cluster to allow you to do spatial analysis on the spatial data within your cluster, and he demonstrated rendering from a data center with ArcGIS Pro, a new product that has a brand new rendering engine.
Jan. 28, 2015 02:30 PM EST Reads: 1,639
The 3rd International Internet of @ThingsExpo, co-located with the 16th International Cloud Expo - to be held June 9-11, 2015, at the Javits Center in New York City, NY - announces that its Call for Papers is now open. The Internet of Things (IoT) is the biggest idea since the creation of the Worldwide Web more than 20 years ago.
Jan. 28, 2015 02:30 PM EST Reads: 2,964
"People are a lot more knowledgeable about APIs now. There are two types of people who work with APIs - IT people who want to use APIs for something internal and the product managers who want to do something outside APIs for people to connect to them," explained Roberto Medrano, Executive Vice President at SOA Software, in this SYS-CON.tv interview at Cloud Expo, held Nov 4–6, 2014, at the Santa Clara Convention Center in Santa Clara, CA.
Jan. 28, 2015 02:30 PM EST Reads: 2,542