|By PR Newswire||
|January 9, 2014 04:32 PM EST||
SAN DIEGO, Jan. 9, 2014 /PRNewswire/ -- Neurocrine Biosciences, Inc. (NASDAQ: NBIX) announced today that NBI-98854, a small molecule VMAT2 inhibitor, in development for tardive dyskinesia, showed an excellent safety profile and a clinically meaningful reduction in tardive dyskinesia symptoms in up to twelve weeks of continuous dosing. This is the second study reporting out this week that demonstrates the potential of NBI-98854 as a safe and highly effective therapy for tardive dyskinesia sufferers. Both of these studies will serve as the foundation for an End of Phase II meeting later this year.
The Kinect study was a randomized, parallel, double-blind, placebo-controlled, Phase IIb clinical trial utilizing the capsule formulation of NBI-98854 in moderate to severe tardive dyskinesia patients with underlying schizophrenia or schizoaffective disorder. The study assessed NBI-98854 over a six-week placebo-controlled dosing period. The top-line results from the placebo-controlled portion were previously reported by the Company in September 2013. Subsequent to the placebo-controlled dosing period, all subjects were eligible to enter a six-week open-label safety extension of 50 mg of NBI-98854 administered once daily, followed by a four-week washout period.
NBI-98854 was generally safe and well tolerated in the Kinect study. During the twelve-week treatment period the frequency of treatment-emergent adverse events was 40% for NBI-98854, similar to previous clinical trials. There were no drug related serious adverse events. The most common treatment-emergent adverse event during the entire twelve-week period was urinary tract infection in six subjects (5.9%) on NBI-98854, which were assessed as not related to study drug by the investigators. All other adverse events occurred at less than a 3% frequency.
Participants were assessed utilizing the Barnes Akathisia Ratings Scale (BARS) for akathisia and the Simpson-Angus Scale (SAS) for parkinsonism. Both of these scales documented minimal symptoms at baseline and were stable to improved during the twelve weeks of treatment. Subjects were also assessed using various safety scales including the Positive and Negative Syndrome Scale (PANSS) for Schizophrenia, the Calgary Depression Scale for Schizophrenia and the Columbia-Suicide Severity Rating Scale (C-SSRS); all of these scores were stable to improved from baseline. Clinical hematology, chemistry and ECG monitoring indicated no emergent safety signals.
There were no drug-drug interactions identified in subjects who were utilizing a range of psychotropic and other concomitant medications.
"We are very pleased with the safety profile of NBI-98854 over twelve weeks of continuous dosing. The drug was generally well tolerated and there were no obvious safety signals," said Christopher F. O'Brien, Chief Medical Officer of Neurocrine Biosciences. "Although this phase of the Kinect study was not placebo-controlled, we are further encouraged by the reduction in tardive dyskinesia through Week 12."
At Week 12, there was a marked reduction from baseline in the Abnormal Involuntary Movement Scale (AIMS) scores for both groups of subjects; those who were initially randomized to NBI-98854 with 12 weeks of continuous dosing and those who were originally randomized to placebo for 6 weeks, then entered the 6-week open-label extension of NBI-98854. The Week 12 responder rate (defined as a 50% or greater reduction in AIMS from baseline) was 54%.
The Week 12 improvement in tardive dyskinesia symptoms was also corroborated by the Clinical Global Impression–Tardive Dyskinesia (CGI-TD). Treating clinicians determined at Week 12 that approximately 61% of the subjects taking NBI-98854 were "much improved" or "very much improved" at Week 12. The twelve-week treatment period was followed by a four-week washout period. At the end of this washout period, only 29% of these same subjects were evaluated by the treating physicians as "much improved" or "very much improved" utilizing the CGI-TD.
"This twelve-week safety and related efficacy data is another important component for our End of Phase II FDA meeting that we plan to request during the first half of 2014," said Kevin C. Gorman, Chief Executive Officer of Neurocrine Biosciences.
The Kinect study randomized 109 subjects; 81 subjects completed Week 12, of which 42 subjects were originally randomized to placebo and 39 were originally randomized to NBI-98854. Similar to the Company's other studies, the average age of the trial participants was 55 years with an average age at onset of tardive dyskinesia of 47 years. Approximately two-thirds of the subjects were male.
Kinect Study Design
The Kinect study was a randomized, parallel, double-blind, placebo-controlled, Phase IIb clinical trial utilizing the capsule formulation of NBI-98854 in moderate to severe tardive dyskinesia patients with underlying schizophrenia or schizoaffective disorder. The study assessed two doses of once-daily NBI-98854 over a six-week placebo-controlled dosing period. Half of the randomized subjects received placebo and half received one of two doses of NBI-98854. The two NBI-98854 dosing groups consisted of a 50mg group for six weeks and a group that began at 100mg for the initial two weeks then converted to 50mg for the final four weeks of the placebo-controlled dosing period. Subsequent to the placebo-controlled dosing, all subjects were eligible to enter a six-week open-label safety extension of 50mg of NBI-98854 administered once daily with additional AIMS assessments. The primary efficacy endpoint of the study was a comparison of placebo and active scores as determined by the on-site AIMS raters at the end of Week 6.
Next Steps for NBI-98854
This Kinect twelve-week data, along with the initial six-week data from the Kinect study will be integrated with the Kinect 2 study data to inform the ultimate design of the next study. The Company will work with its consultants and scientific advisors to expand and refine the pharmacokinetic/pharmacodynamic models as well as to complete the remaining safety and efficacy analyses from both Kinect and Kinect 2. These data will form the basis for an End of Phase II briefing package along with the proposed Phase III protocol.
About Tardive Dyskinesia
Tardive dyskinesia is characterized by involuntary, repetitive movements of the extremities: lip smacking, grimacing, tongue protrusion, facial movements or blinking, puckering and pursing of the lips, or involuntary movements of the limbs. These symptoms are rarely reversible and there is currently no approved treatment.
VMAT2 is a protein concentrated in the human brain that is primarily responsible for re-packaging and transporting monoamines (dopamine, norepinephrine, serotonin, and histamine) in pre-synaptic neurons. NBI-98854, developed in the Neurocrine laboratories, is a novel, highly-selective VMAT2 inhibitor that modulates dopamine release during nerve communication, while at the same time having minimal impact on the other monoamines, thereby reducing the likelihood of "off target" side effects. NBI-98854 is designed to provide low, sustained, plasma and brain concentrations of active drug to minimize side effects associated with excessive monoamine depletion. The Company has completed nine-month in-vivo toxicology studies to support longer dosing regimens in humans.
NBI-98854 may also be useful in other disorders such as Huntington's chorea, schizophrenia, Tourette's syndrome, and tardive dystonia.
About Neurocrine Biosciences
Neurocrine Biosciences, Inc. is a clinical stage drug discovery company primarily focused on neurological and endocrine based diseases and disorders. The Company discovers and develops innovative pharmaceuticals, in diseases with high unmet medical needs or where the existing drug classes are inadequate, through a disciplined yet entrepreneurial process. Utilizing a portfolio approach to drug discovery, Neurocrine has multiple small molecule drug candidates at various stages of pharmaceutical development. Neurocrine's two lead late stage clinical programs are elagolix, a GnRH antagonist for women's health that is partnered with AbbVie Inc., and a wholly owned VMAT2 inhibitor for the treatment of movement disorders. Neurocrine Biosciences, Inc. news releases are available through the Company's website via the internet at http://www.neurocrine.com.
In addition to historical facts, this press release may contain forward-looking statements that involve a number of risks and uncertainties. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements are risks and uncertainties associated with Neurocrine's business and finances in general, as well as risks and uncertainties associated with the Company's VMAT2 program and Company overall. Specifically, the risks and uncertainties the Company faces with respect to the Company's VMAT2 program include, but are not limited to; risk that NBI-98854 will not proceed to later stage clinical trials and risk that the Company's clinical trials will fail to demonstrate that NBI-98854 is safe and effective. With respect to its pipeline overall, the Company faces risk that it will be unable to raise additional funding required to complete development of all of its product candidates; risk relating to the Company's dependence on contract manufacturers for clinical drug supply; risks associated with the Company's dependence on corporate partners for development, commercial manufacturing and marketing and sales activities for the Company's partnered programs; uncertainties relating to patent protection and intellectual property rights of third parties; risks and uncertainties relating to competitive products and technological changes that may limit demand for the Company's products; and the other risks described in the Company's report on Form 10-K for the year ended December 31, 2012 and on Form 10-Q for the quarter ended September 30, 2013. Neurocrine undertakes no obligation to update the statements contained in this press release after the date hereof.
SOURCE Neurocrine Biosciences, Inc.
“The Internet of Things transforms the way organizations leverage machine data and gain insights from it,” noted Splunk’s CTO Snehal Antani, as Splunk announced accelerated momentum in Industrial Data and the IoT. The trend is driven by Splunk’s continued investment in its products and partner ecosystem as well as the creativity of customers and the flexibility to deploy Splunk IoT solutions as software, cloud services or in a hybrid environment. Customers are using Splunk® solutions to collect ...
Oct. 6, 2015 01:00 PM EDT Reads: 579
Recently announced Azure Data Lake addresses the big data 3V challenges; volume, velocity and variety. It is one more storage feature in addition to blobs and SQL Azure database. Azure Data Lake (should have been Azure Data Ocean IMHO) is really omnipotent. Just look at the key capabilities of Azure Data Lake:
Oct. 6, 2015 01:00 PM EDT Reads: 199
SYS-CON Events announced today that ProfitBricks, the provider of painless cloud infrastructure, will exhibit at SYS-CON's 17th International Cloud Expo®, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. ProfitBricks is the IaaS provider that offers a painless cloud experience for all IT users, with no learning curve. ProfitBricks boasts flexible cloud servers and networking, an integrated Data Center Designer tool for visual control over the...
Oct. 6, 2015 01:00 PM EDT Reads: 731
Scott Guthrie's keynote presentation "Journey to the intelligent cloud" is a must view video. This is from AzureCon 2015, September 29, 2015 I have reproduced some screen shots in case you are unable to view this long video for one reason or another. One of the highlights is 3 datacenters coming on line in India.
Oct. 6, 2015 01:00 PM EDT Reads: 216
When it comes to IoT in the enterprise, namely the commercial building and hospitality markets, a benefit not getting the attention it deserves is energy efficiency, and IoT’s direct impact on a cleaner, greener environment when installed in smart buildings. Until now clean technology was offered piecemeal and led with point solutions that require significant systems integration to orchestrate and deploy. There didn't exist a 'top down' approach that can manage and monitor the way a Smart Buildi...
Oct. 6, 2015 01:00 PM EDT Reads: 230
You have your devices and your data, but what about the rest of your Internet of Things story? Two popular classes of technologies that nicely handle the Big Data analytics for Internet of Things are Apache Hadoop and NoSQL. Hadoop is designed for parallelizing analytical work across many servers and is ideal for the massive data volumes you create with IoT devices. NoSQL databases such as Apache HBase are ideal for storing and retrieving IoT data as “time series data.”
Oct. 6, 2015 12:45 PM EDT Reads: 456
SYS-CON Events announced today that G2G3 will exhibit at SYS-CON's @DevOpsSummit Silicon Valley, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. Based on a collective appreciation for user experience, design, and technology, G2G3 is uniquely qualified and motivated to redefine how organizations and people engage in an increasingly digital world.
Oct. 6, 2015 12:30 PM EDT Reads: 278
Clearly the way forward is to move to cloud be it bare metal, VMs or containers. One aspect of the current public clouds that is slowing this cloud migration is cloud lock-in. Every cloud vendor is trying to make it very difficult to move out once a customer has chosen their cloud. In his session at 17th Cloud Expo, Naveen Nimmu, CEO of Clouber, Inc., will advocate that making the inter-cloud migration as simple as changing airlines would help the entire industry to quickly adopt the cloud wit...
Oct. 6, 2015 12:30 PM EDT Reads: 572
As the world moves towards more DevOps and microservices, application deployment to the cloud ought to become a lot simpler. The microservices architecture, which is the basis of many new age distributed systems such as OpenStack, NetFlix and so on, is at the heart of Cloud Foundry - a complete developer-oriented Platform as a Service (PaaS) that is IaaS agnostic and supports vCloud, OpenStack and AWS. In his session at 17th Cloud Expo, Raghavan "Rags" Srinivas, an Architect/Developer Evangeli...
Oct. 6, 2015 12:15 PM EDT
SYS-CON Events announced today that VividCortex, the monitoring solution for the modern data system, will exhibit at the 17th International Cloud Expo®, which will take place on November 3–5, 2015, at the Santa Clara Convention Center in Santa Clara, CA. The database is the heart of most applications, but it’s also the part that’s hardest to scale, monitor, and optimize even as it’s growing 50% year over year. VividCortex is the first unified suite of database monitoring tools specifically desi...
Oct. 6, 2015 12:00 PM EDT Reads: 405
Organizations already struggle with the simple collection of data resulting from the proliferation of IoT, lacking the right infrastructure to manage it. They can't only rely on the cloud to collect and utilize this data because many applications still require dedicated infrastructure for security, redundancy, performance, etc. In his session at 17th Cloud Expo, Emil Sayegh, CEO of Codero Hosting, will discuss how in order to resolve the inherent issues, companies need to combine dedicated a...
Oct. 6, 2015 12:00 PM EDT Reads: 433
Mobile, social, Big Data, and cloud have fundamentally changed the way we live. “Anytime, anywhere” access to data and information is no longer a luxury; it’s a requirement, in both our personal and professional lives. For IT organizations, this means pressure has never been greater to deliver meaningful services to the business and customers.
Oct. 6, 2015 12:00 PM EDT Reads: 282
Cloud computing delivers on-demand resources that provide businesses with flexibility and cost-savings. The challenge in moving workloads to the cloud has been the cost and complexity of ensuring the initial and ongoing security and regulatory (PCI, HIPAA, FFIEC) compliance across private and public clouds. Manual security compliance is slow, prone to human error, and represents over 50% of the cost of managing cloud applications. Determining how to automate cloud security compliance is critical...
Oct. 6, 2015 12:00 PM EDT Reads: 241
In his session at @ThingsExpo, Tony Shan, Chief Architect at CTS, will explore the synergy of Big Data and IoT. First he will take a closer look at the Internet of Things and Big Data individually, in terms of what, which, why, where, when, who, how and how much. Then he will explore the relationship between IoT and Big Data. Specifically, he will drill down to how the 4Vs aspects intersect with IoT: Volume, Variety, Velocity and Value. In turn, Tony will analyze how the key components of IoT ...
Oct. 6, 2015 12:00 PM EDT Reads: 274
DevOps is gaining traction in the federal government – and for good reasons. Heightened user expectations are pushing IT organizations to accelerate application development and support more innovation. At the same time, budgetary constraints require that agencies find ways to decrease the cost of developing, maintaining, and running applications. IT now faces a daunting task: do more and react faster than ever before – all with fewer resources.
Oct. 6, 2015 12:00 PM EDT Reads: 333