SAN DIEGO,
Oct. 8, 2015 /PRNewswire/ -- Neurocrine Biosciences,
Inc. (NASDAQ: NBIX) announced today that NBI-98854, a highly
selective small molecule VMAT2 inhibitor, showed a statistically
significant reduction in tardive dyskinesia during the six weeks of
placebo-controlled treatment in the Kinect 3 clinical trial. This
Phase III trial included moderate to severe tardive dyskinesia
patients with underlying schizophrenia, schizoaffective disorder,
bipolar or major depressive disorder.
The pre-specified primary efficacy endpoint was the
change-from-baseline in the Abnormal Involuntary Movement Scale
(AIMS) at Week 6 in the 80mg once-daily dosing group compared to
placebo as assessed by central blinded video raters. The AIMS
ratings at Week 6 for the 80mg once-daily NBI-98854
intention-to-treat (ITT) population was reduced 3.1 points
(Least-Squares Mean) more than placebo (p<0.0001).
"We are very pleased with the outstanding efficacy and side
effect profile demonstrated by NBI-98854 in the Kinect 3 study. The
efficacy data from this pivotal Phase III study completes our
placebo-controlled dataset for NBI-98854 in tardive dyskinesia,"
said Kevin C. Gorman, President and
Chief Executive Officer of Neurocrine. "We will now turn our focus
to completing the open-label safety portion of the studies in
tardive dyskinesia patients and compiling the data for both doses
of NBI-98854 to be included in the New Drug Application we intend
to file with the FDA in 2016."
"The results of this Kinect 3 study demonstrate the potential of
NBI-98854 to be a safe and effective treatment for patients
suffering from the debilitating effects of tardive dyskinesia and
we look forward to sharing additional details of this important
study at upcoming scientific meetings starting in mid-2016," said
Christopher F. O'Brien, Chief
Medical Officer of Neurocrine. "We want to thank the trial
participants and investigators who contributed to this successful
placebo-controlled portion of the Kinect 3 study and we look
forward to continuing our work with them in the open-label safety
assessment of NBI-98854 in patients suffering from tardive
dyskinesia, as well as completing the initial Tourette syndrome
study later this year."
In addition to the primary efficacy endpoint, the AIMS rating
for the 40mg once-daily dose and the Clinical Global Impression of
Change (CGI-TD) for both doses were also evaluated. The table below
summarizes the results of the AIMS ratings and CGI-TD at Week 6 for
both the ITT population and a preliminary pre-specified
per-protocol (PP) population. The PP population excluded subjects
whose plasma concentrations of NBI-98854 were below the lower limit
of quantitation (i.e., not detectable). Given the timing of plasma
samples collections and the pharmacokinetic profile of NBI-98854,
it was determined that these subjects had not ingested the study
drug.
|
|
Week
6
|
|
|
40mg
qd
|
p-value*
|
80mg
qd
|
p-value*
|
AIMS Difference
from Placebo
|
|
Least-Squares Mean
(ITT population)
|
-1.8
|
0.0021
|
-3.1
|
<0.0001
|
|
Least-Squares Mean
(PP population)
|
-2.1
|
0.0009
|
-3.6
|
<0.0001
|
|
|
|
|
|
|
CGI-TD Difference
from Placebo
|
|
Least-Squares Mean
(ITT population)
|
-0.3
|
0.0742
|
-0.3
|
0.0560
|
|
Least-Squares Mean
(PP population)
|
-0.4
|
0.0097
|
-0.4
|
0.0122
|
|
|
*
|
Assessment of the
significance of p-values based on pre-specified, fixed-sequence
testing procedure
|
Safety Profile
During the six-week placebo-controlled treatment period
NBI-98854 was generally well tolerated. The frequency of adverse
events was similar among all treatment groups and treatment
emergent adverse effects were consistent with those of prior
studies.
Participants were also 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 there was no worsening during the six
weeks of treatment. Clinical hematology, chemistry and ECG
monitoring indicated no emergent safety signals.
There were no drug-drug interactions identified in subjects who
were utilizing a wide range of psychotropic and other concomitant
medications.
Kinect 3 Study Design
The Kinect 3 study (ClinicalTrials.gov Identifier NCT02274558)
is a randomized, parallel-group, double-blind, placebo-controlled,
Phase III clinical trial utilizing the capsule formulation of
NBI-98854 in moderate to severe tardive dyskinesia patients with
underlying schizophrenia, schizoaffective disorder or mood disorder
(including bipolar disorder or major depressive disorder). The
Kinect 3 study randomized 234 subjects to either placebo,
once-daily 40mg of NBI-98854 or once-daily 80mg of NBI-98854
for six weeks. Subsequent to the completion of the six
week placebo-controlled dosing, all subjects are placed
on once-daily 40mg or once-daily 80mg of NBI-98854 through
Week 48.
The Kinect 3 study, along with the previous efficacy studies of
NBI-98854, is designed to complete the placebo-controlled clinical
efficacy evaluation of NBI-98854 in tardive dyskinesia. In addition
to Kinect 3, a separate one-year open-label safety study of
NBI-98854, Kinect 4, has also been initiated to support the
anticipated 2016 filing of a New Drug Application in tardive
dyskinesia.
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 are currently no approved
treatments.
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.
Modulation of neuronal dopamine levels in diseases such as
tardive dyskinesia, Tourette syndrome, Huntington's chorea,
schizophrenia, and tardive dystonia, which are characterized, in
part, by a hyperdopaminergic state, should provide symptomatic
benefits for patients with these diseases.
As announced previously, Neurocrine has also received
Breakthrough Therapy Designation from the FDA for NBI-98854 in the
treatment of tardive dyskinesia.
The Company is also exploring NBI-98854 in an initial Tourette
syndrome clinical trial, the T-Force study. This study is an
open-label, multi-dose, two-week evaluation of up to 36 subjects
with Tourette syndrome. Children and adolescents enrolled in the
trial are receiving a once-daily dose of NBI-98854 during a
two-week treatment period to assess both the safety and
tolerability of NBI-98854. Additionally, the Yale Global Tic
Severity Scale and the Premonitory Urge for Tics Scale are being
utilized during the study to assess the impact of NBI-98854 on the
patients' Tourette symptoms. Data read out from the T-Force study
is expected later in 2015.
Conference Call and Webcast Today at 8:00AM Eastern Time
Neurocrine will hold a live conference call and webcast today at
8:00 a.m. Eastern Time (5:00 a.m. Pacific Time). Participants can access
the live conference call by dialing 866-952-1906 (US) or
785-424-1825 (International) using the conference ID: NBIX. The
call can also be accessed via the webcast through the Company's
website at http://www.neurocrine.com.
If you are unable to attend the webcast and would like further
information on this announcement please contact the Investor
Relations Department at Neurocrine Biosciences at (858)
617-7600. A replay of the conference call will be available
approximately one hour after the conclusion of the call by dialing
800-839-1247(US) or 402-220-0470 (International) using the
conference ID: NBIX. The call will be archived for one month.
Neurocrine Biosciences, Inc. discovers and develops innovative
and life-changing pharmaceuticals, in diseases with high unmet
medical needs, through its novel R&D platform, focused on
neurological and endocrine based diseases and disorders. The
Company's two lead late-stage clinical programs are elagolix, a
gonadotropin-releasing hormone antagonist for women's health that
is partnered with AbbVie Inc., and NBI-98854, a vesicular monoamine
transporter 2 inhibitor for the treatment of movement disorders.
Neurocrine intends to maintain certain commercial rights to its
VMAT2 inhibitor for evolution into a fully-integrated
pharmaceutical company.
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 NBI-98854 development.
Specifically, the risks and uncertainties the Company faces include
risks that NBI-98854 development activities may not be completed on
time or at all; risks that NBI-98854 development activities may be
delayed for regulatory or other reasons, may not be successful or
replicate previous clinical trial results, may fail to demonstrate
that NBI-98854 is safe and effective, or may not be predictive of
real-world results or of results in subsequent clinical trials;
risks that NBI-98854 regulatory submissions may not occur or be
submitted in a timely manner; risks that NBI-98854 may not
obtain regulatory approval or that the U.S. Food and Drug
Administration or regulatory authorities outside the U.S. may make
adverse decisions regarding NBI-98854; risks that NBI-98854 may be
precluded from commercialization by the proprietary rights of third
parties, or have unintended side effects, adverse reactions or
incidents of misuse; risks associated with the Company's dependence
on third parties for development and manufacturing activities
related to NBI-98854; risks that the Company will be unable to
raise additional funding, if required, to complete development of
NBI-98854; risk and uncertainties relating to competitive products
and technological changes that may limit demand for NBI-98854; and
other risks described in the Company's quarterly report on Form
10-Q for the quarter ended June 30,
2015. Neurocrine disclaims any obligation to update the
statements contained in this press release after the date
hereof.
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SOURCE Neurocrine Biosciences, Inc.