|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.
Companies can harness IoT and predictive analytics to sustain business continuity; predict and manage site performance during emergencies; minimize expensive reactive maintenance; and forecast equipment and maintenance budgets and expenditures. Providing cost-effective, uninterrupted service is challenging, particularly for organizations with geographically dispersed operations.
May. 27, 2016 06:00 PM EDT Reads: 2,012
SYS-CON Events announced today that Commvault, a global leader in enterprise data protection and information management, has been named “Bronze Sponsor” of 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, and the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Commvault is a leading provider of data protection and information management...
May. 27, 2016 06:00 PM EDT Reads: 3,121
How will your company move to the cloud while ensuring a solid security posture? Organizations from small to large are increasingly adopting cloud solutions to deliver essential business services at a much lower cost. According to cyber security experts, the frequency and severity of cyber-attacks are on the rise, causing alarm to businesses and customers across a variety of industries. To defend against exploits like these, a company must adopt a comprehensive security defense strategy that is ...
May. 27, 2016 05:15 PM EDT Reads: 322
SYS-CON Events announced today that Tintri Inc., a leading producer of VM-aware storage (VAS) for virtualization and cloud environments, will exhibit at the 18th International CloudExpo®, which will take place on June 7-9, 2016, at the Javits Center in New York City, New York, and the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
May. 27, 2016 05:00 PM EDT Reads: 2,351
SYS-CON Events announced today that BMC Software has been named "Siver Sponsor" of SYS-CON's 18th Cloud Expo, which will take place on June 7-9, 2015 at the Javits Center in New York, New York. BMC is a global leader in innovative software solutions that help businesses transform into digital enterprises for the ultimate competitive advantage. BMC Digital Enterprise Management is a set of innovative IT solutions designed to make digital business fast, seamless, and optimized from mainframe to mo...
May. 27, 2016 04:45 PM EDT Reads: 2,168
Customer experience has become a competitive differentiator for companies, and it’s imperative that brands seamlessly connect the customer journey across all platforms. With the continued explosion of IoT, join us for a look at how to build a winning digital foundation in the connected era – today and in the future. In his session at @ThingsExpo, Chris Nguyen, Group Product Marketing Manager at Adobe, will discuss how to successfully leverage mobile, rapidly deploy content, capture real-time d...
May. 27, 2016 04:45 PM EDT Reads: 1,553
SYS-CON Events announced today that EastBanc Technologies 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. EastBanc Technologies has been working at the frontier of technology since 1999. Today, the firm provides full-lifecycle software development delivering flexible technology solutions that seamlessly integrate with existing systems – whether on premise or cloud. EastBanc Technologies partners with p...
May. 27, 2016 04:30 PM EDT Reads: 2,242
SYS-CON Events announced today that AppNeta, the leader in performance insight for business-critical web applications, will exhibit and present at SYS-CON's @DevOpsSummit at Cloud Expo New York, which will take place on June 7-9, 2016, at the Javits Center in New York City, NY. AppNeta is the only application performance monitoring (APM) company to provide solutions for all applications – applications you develop internally, business-critical SaaS applications you use and the networks that deli...
May. 27, 2016 04:00 PM EDT Reads: 2,462
SoftLayer operates a global cloud infrastructure platform built for Internet scale. With a global footprint of data centers and network points of presence, SoftLayer provides infrastructure as a service to leading-edge customers ranging from Web startups to global enterprises. SoftLayer's modular architecture, full-featured API, and sophisticated automation provide unparalleled performance and control. Its flexible unified platform seamlessly spans physical and virtual devices linked via a world...
May. 27, 2016 03:30 PM EDT Reads: 2,180
SYS-CON Events announced today that ContentMX, the marketing technology and services company with a singular mission to increase engagement and drive more conversations for enterprise, channel and SMB technology marketers, has been named “Sponsor & Exhibitor Lounge Sponsor” of SYS-CON's 18th Cloud Expo, which will take place on June 7-9, 2016, at the Javits Center in New York City, New York. “CloudExpo is a great opportunity to start a conversation with new prospects, but what happens after the...
May. 27, 2016 03:30 PM EDT Reads: 1,110
In the rush to compete in the digital age, a successful digital transformation is essential, but many organizations are setting themselves up for failure. There’s a common misconception that the process is just about technology, but it’s not. It’s about your business. It shouldn’t be treated as an isolated IT project; it should be driven by business needs with the committed involvement of a range of stakeholders.
May. 27, 2016 03:00 PM EDT Reads: 2,460
SYS-CON Events announced today that Isomorphic Software will exhibit at SYS-CON's [email protected] at Cloud Expo New York, which will take place on June 7-9, 2016, at the Javits Center in New York City, NY. Isomorphic Software provides the SmartClient HTML5/AJAX platform, the most advanced technology for building rich, high-productivity enterprise web applications for any device. SmartClient couples the industry’s broadest, deepest UI component set with a java server framework to deliver an end-...
May. 27, 2016 03:00 PM EDT Reads: 2,144
As machines are increasingly connected to the internet, it’s becoming easier to discover the numerous ways Industrial IoT (IIoT) is helping to shape the business world. This is exactly why we have decided to take a closer look at this pervasive movement and to examine the desire to connect more things! Now if you need a refresher on IIoT and how it is changing the world, take a moment and listen to Greg Gorbach with ARC Advisory Group. Gorbach believes, "IIoT will significantly change the worl...
May. 27, 2016 03:00 PM EDT Reads: 1,924
The cloud era has reached the stage where it is no longer a question of whether a company should migrate, but when. Enterprises have embraced the outsourcing of where their various applications are stored and who manages them, saving significant investment along the way. Plus, the cloud has become a defining competitive edge. Companies that fail to successfully adapt risk failure. The media, of course, continues to extol the virtues of the cloud, including how easy it is to get there. Migrating...
May. 27, 2016 03:00 PM EDT Reads: 402
The IoT is changing the way enterprises conduct business. In his session at @ThingsExpo, Eric Hoffman, Vice President at EastBanc Technologies, discuss how businesses can gain an edge over competitors by empowering consumers to take control through IoT. We'll cite examples such as a Washington, D.C.-based sports club that leveraged IoT and the cloud to develop a comprehensive booking system. He'll also highlight how IoT can revitalize and restore outdated business models, making them profitable...
May. 27, 2016 12:30 PM EDT Reads: 2,831