SAN DIEGO, Oct. 4, 2019 /PRNewswire/ -- Neurocrine
Biosciences, Inc. (NASDAQ: NBIX) today announced data from pooled
analyses demonstrating the long-term benefit of the once-daily 40
mg dose of INGREZZA® (valbenazine) capsules in reducing
abnormal movements in adults with tardive dyskinesia (TD), a
potentially irreversible and often persistent involuntary movement
disorder. The analyses of pooled data from multiple long-term
studies of the 40 mg dose showed that 53.7% of patients taking 40
mg of INGREZZA achieved an Abnormal Involuntary Movement Scale (AIMS) response (≥ 50%
improvement from baseline) after 48 weeks of treatment. INGREZZA is
available in two doses, 40 mg and 80 mg. Additionally, an analysis
of the pivotal Phase III KINECT 3 data demonstrated that 50% of
patients achieved an early response after two weeks of INGREZZA
treatment (40 mg or 80 mg). Data also showed that meaningful
long-term reductions in TD were achieved regardless of whether
patients responded after two weeks. These long-term INGREZZA data
were presented today at the 2019 Annual Psych Congress in
San Diego.
"Tardive dyskinesia is a persistent and often irreversible
movement disorder, and it can look and feel different from one
patient to another, with each patient having distinct treatment
needs," said Craig Chepke, M.D.,
Adjunct Assistant Professor of Psychiatry, University of North Carolina School of Medicine.
"Long-term data from the pooled analyses are important as they show
that the 40 mg dose of INGREZZA is effective in reducing the
troublesome movements of tardive dyskinesia in over 50% of
patients. Many patients feel embarrassed, endure social isolation
and experience even greater stigma associated with their existing
mental illness, so having two effective dosing options of INGREZZA
gives healthcare providers a choice in what will work best to
manage the burdensome and disruptive involuntary movements
associated with tardive dyskinesia."
INGREZZA is the first U.S. Food and Drug Administration (FDA)
approved treatment for adults with TD, a movement disorder that is
characterized by uncontrollable, abnormal and repetitive movements
of the face, torso and/or other body parts. The abnormal and
involuntary movements of TD can impact patients socially,
emotionally and physically, causing patients to feel embarrassed or
judged by others or withdraw from society and isolate
themselves.
"The analyses of pooled data continue to support the growing
body of evidence that INGREZZA is an effective treatment for the
long-term management of tardive dyskinesia," said Eiry W. Roberts,
M.D., Chief Medical Officer at Neurocrine Biosciences. "It is
important to choose the best dosing option of INGREZZA and continue
treatment to achieve long-term outcomes as tardive dyskinesia
varies from patient to patient as well as their treatment
response."
Data from pooled analyses of long-term clinical studies, KINECT
3 and KINECT 4, showed that 53.7% of patients taking 40 mg of
INGREZZA (n=54) achieved an AIMS response (≥ 50% improvement from
baseline) after 48 weeks of treatment and 65.5% of patients (n=55)
demonstrated a Clinical Global
Impression of Change-Tardive Dyskinesia (CGI-TD) response (defined
as "very much improved" or "much improved"). Additionally, dose
reductions from 80 mg to 40 mg did not appear to compromise the
long-term benefit of INGREZZA.
Neurocrine Biosciences also presented a post-hoc analysis of
KINECT 3, the pivotal Phase III study, indicating that both the 40
mg and 80 mg doses of INGREZZA improved TD as early as two weeks in
adults with TD, as measured by global clinician and patient scales.
Results showed that 50% of patients (n=143) reached an early
response threshold by patient-reported assessment (Patient Global
Impression of Change [PGIC]; score ≤ 3 at Week 2), while 43%
achieved an early response by clinician judgement (CGI-TD; score ≤ 3 at Week 2). Long-term
reductions in TD symptom severity were meaningful regardless of
early response as indicated by both PGIC and CGI-TD
improvement.
In the studies, INGREZZA was generally well tolerated with no
new safety concerns observed, and patients had no notable worsening
of psychiatric symptoms. The most common adverse reactions (≥5% and
twice the rate of placebo) during the 6-week double-blind,
placebo-controlled phase was somnolence.
About the KINECT 3 Phase III Study
KINECT 3 is a Phase
III, randomized, double-blind, placebo-controlled, parallel-group,
fixed-dose study, in which 234 participants with moderate to severe
TD and underlying schizophrenia, schizoaffective disorder or mood
disorder (including bipolar disorder or major depressive disorder)
received six weeks of once-daily INGREZZA (40 mg or 80 mg capsules)
or placebo (participants randomized to 80 mg started on 40 mg for 1
week). Subsequent to the completion of the six-week
placebo-controlled dosing, participants receiving INGREZZA
continued on their current dose and placebo participants were
randomized to receive either once-daily 40 mg or once-daily 80 mg
of INGREZZA, through week 48 (42-week blinded treatment extension
period; placebo participants randomized to 80 mg started on 40 mg
for 1 week), followed by a 4-week drug-free washout. Dose reduction
to 40 mg was allowed for participants who were unable to tolerate
the 80 mg dose. Patients were discontinued if the new dose was not
tolerated.
The study met its primary endpoint of change-from-baseline in
AIMS at week six in the 80 mg once-daily dosing group compared to
placebo as assessed by expert central blinded video raters. The
mean change from baseline to week six in the AIMS rating was -3.2
for the 80 mg once-daily group as compared to -0.1 in the placebo
group (p>0.0001). Sustained TD improvements were seen with
INGREZZA 40 mg and 80 mg through week 48.
INGREZZA was generally well tolerated throughout 48 weeks of
treatment. The most common adverse reactions (≥5% and twice the
rate of placebo) during the 6-week double-blind, placebo-controlled
phase was somnolence with the frequency of adverse events being
similar among all treatment groups. Treatment emergent adverse
events (TEAEs) were consistent with those of prior studies. There
were no drug-drug interactions identified in participants who were
utilizing a wide range of psychotropic and other concomitant
medications and participants generally remained psychiatrically
stable throughout the study.
About the KINECT 4 Phase III Study
KINECT 4 is a Phase
III, open-label study, in which 163 participants with
moderate-to-severe TD and underlying schizophrenia, schizoaffective
disorder or mood disorder (including bipolar disorder or major
depressive disorder) received 48 weeks of open-label treatment with
once-daily INGREZZA (40 mg or 80 mg capsules) followed by a 4-week
washout. Dosing was initiated at 40 mg/day in all participants,
with escalation to 80 mg/day at week 4 based on effectiveness and
tolerability. Dose reduction to 40 mg was allowed in participants
who could not tolerate the 80 mg dose. Patients were discontinued
if the new dose was not tolerated.
Participants experienced TD improvements during long-term
treatment as demonstrated by mean change from baseline to week 48
in AIMS total score (sum of items 1-7, evaluated by site raters)
with INGREZZA 40 mg/day (-10.2) or 80 mg/day (-11.0). Consistent
with previous studies, INGREZZA was generally well tolerated. After
week 4, TEAEs that occurred in ≥5% of all participants (combined
dose groups) were urinary tract infection (8.5%) and headache
(5.2%). Change from baseline in psychiatric stability, vital signs,
electrocardiogram parameters, and laboratory test values were
generally small and not clinically significant.
About Tardive Dyskinesia (TD)
Tardive dyskinesia (TD)
is a movement disorder that is characterized by uncontrollable,
abnormal and repetitive movements of the face, torso and/or other
body parts, which may be disruptive and negatively impact patients.
The condition is caused by prolonged use of treatments that block
dopamine receptors in the brain, such as antipsychotics commonly
prescribed to treat mental illnesses such as schizophrenia, bipolar
disorder and depression, and certain anti-nausea medications. In
patients with TD, these treatments are thought to result in
irregular dopamine signaling in a region of the brain that controls
movement. The symptoms of TD can be severe and are often persistent
and irreversible. TD is estimated to affect at least 500,000 people
in the U.S.
About INGREZZA® (valbenazine)
Capsules
INGREZZA, a selective vesicular monoamine
transporter 2 (VMAT2) inhibitor, is the first FDA-approved product
indicated for the treatment of adults with tardive dyskinesia, a
condition associated with uncontrollable, abnormal and repetitive
movements of the face, torso and/or other body parts.
INGREZZA is thought to work by reducing the amount of dopamine
released in a region of the brain that controls movement and motor
function, helping to regulate nerve signaling in adults with
tardive dyskinesia. VMAT2 is a protein in the brain that packages
neurotransmitters, such as dopamine, for transport and release in
presynaptic neurons. INGREZZA, developed in Neurocrine's
laboratories, is novel in that it selectively inhibits VMAT2 with
no appreciable binding affinity for VMAT1, dopaminergic (including
D2), serotonergic, adrenergic, histaminergic, or muscarinic
receptors. Additionally, INGREZZA can be taken for the treatment of
tardive dyskinesia as one capsule, once-daily, together with
psychiatric medications such as antipsychotics or
antidepressants.
Important Safety Information
Contraindications
INGREZZA is contraindicated in
patients with a history of hypersensitivity to valbenazine or any
components of INGREZZA. Rash, urticaria, and reactions consistent
with angioedema (e.g., swelling of the face, lips, and mouth) have
been reported.
Warnings & Precautions
Somnolence
INGREZZA can cause somnolence. Patients
should not perform activities requiring mental alertness such as
operating a motor vehicle or operating hazardous machinery until
they know how they will be affected by INGREZZA.
QT Prolongation
INGREZZA may prolong the QT interval, although the degree of QT
prolongation is not clinically significant at concentrations
expected with recommended dosing. INGREZZA should be avoided in
patients with congenital long QT syndrome or with arrhythmias
associated with a prolonged QT interval. For patients at increased
risk of a prolonged QT interval, assess the QT interval before
increasing the dosage.
Parkinsonism
INGREZZA may cause parkinsonism in
patients with tardive dyskinesia. Parkinsonism has also been
observed with other VMAT2 inhibitors. Reduce the dose or
discontinue INGREZZA treatment in patients who develop clinically
significant parkinson-like signs or symptoms.
Adverse Reactions
The most common adverse reaction (≥5% and twice the rate of
placebo) is somnolence. Other adverse reactions (≥2% and
>placebo) include: anticholinergic effects, balance
disorders/falls, headache, akathisia, vomiting, nausea, and
arthralgia.
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit MedWatch
at www.fda.gov/medwatch or call
1-800-FDA-1088.
Please see INGREZZA full Prescribing Information
at www.INGREZZA.com/PI.
About Neurocrine Biosciences, Inc.
Neurocrine Biosciences (Nasdaq: NBIX) is a neuroscience-focused,
biopharmaceutical company with more than 25 years of experience
discovering and developing life-changing treatments for people
with serious, challenging and under-addressed neurological,
endocrine and psychiatric disorders. The company's diverse
portfolio includes FDA-approved treatments for tardive dyskinesia
and endometriosis* and clinical development programs in multiple
therapeutic areas including Parkinson's disease, congenital adrenal
hyperplasia, uterine fibroids* and polycystic ovary
syndrome*. Headquartered in San
Diego, Neurocrine Biosciences specializes in targeting and
interrupting disease-causing mechanisms involving the
interconnected pathways of the nervous and endocrine
systems. For more information, visit neurocrine.com, and
follow the company on LinkedIn. (*in
collaboration with AbbVie)
Forward-Looking Statements
In addition to
historical facts, this press release contains forward-looking
statements that involve a number of risks and uncertainties. These
statements include, but are not limited to, statements related to
the benefits to be derived by patients from INGREZZA. 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 the commercialization of INGREZZA;
risks associated with the Company's dependence on third parties for
development and manufacturing activities related to INGREZZA, and
the ability of the Company to manage these third parties; risks
that the FDA or other regulatory authorities may make adverse
decisions regarding INGREZZA; risks that clinical 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 our product candidates are safe and
effective, or may not be predictive of real-world results or of
results in subsequent clinical trials; risks that INGREZZA may be
precluded from commercialization or continued commercialization by
the proprietary or regulatory rights of third parties, or have
unintended side effects, adverse reactions or incidents of misuse;
and other risks described in the Company's periodic reports filed
with the Securities and Exchange Commission, including without
limitation the Company's quarterly report on Form 10-Q for the
quarter ended June 30, 2019.
Neurocrine disclaims any obligation to update the statements
contained in this press release after the date hereof.
View original content to download
multimedia:http://www.prnewswire.com/news-releases/neurocrine-biosciences-presents-new-data-analyses-demonstrating-long-term-effects-of-ingrezza-valbenazine-40-mg-once-daily-in-patients-with-tardive-dyskinesia-at-the-2019-annual-psych-congress-300931489.html
SOURCE Neurocrine Biosciences, Inc.