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."
Efficacy Profile
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.
Subject Profile
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.
About NBI-98854
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.