SAN DIEGO, Nov. 12, 2019 /PRNewswire/ -- Neurocrine
Biosciences, Inc. (NASDAQ: NBIX) today announced that the
Journal of Clinical Psychopharmacology1
published long-term data from the KINECT 4 Phase III, open-label
study of INGREZZA® (valbenazine) capsules, demonstrating
that treatment with once-daily 40 mg or 80 mg of INGREZZA reduced
involuntary movements in adults who had moderate or severe tardive
dyskinesia (TD) and clinical diagnoses of schizophrenia,
schizoaffective disorder or a mood disorder.
Approximately 90% of patients receiving 40 mg (90.0%) or 80 mg
(89.2%) of INGREZZA achieved ≥50% improvement from baseline as
measured by the Abnormal Involuntary Movement Scale (AIMS) total
score at 48 weeks of treatment and 89-95% of patients achieved a
Clinical Global Impression of Change-TD (CGI-TD) or Patient Global
Impression of Change (PGIC) response of "much improved" or "very
much improved." INGREZZA was generally well tolerated with no new
safety concerns observed, and patients had no notable worsening of
psychiatric symptoms.
"Data from this open-label study, which may be more reflective
of actual clinical practice, provide clinicians with a better
understanding of how INGREZZA can reduce the symptoms of tardive
dyskinesia based on both the clinician's and patient's assessment
of the patient's symptoms, tolerability and response," said
Stephen Marder, M.D., Professor,
Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles. "Tardive
dyskinesia is a persistent and often irreversible movement disorder
that presents differently from patient to patient and as a result,
each patient has unique treatment needs. In this long-term study,
it is evident that both dosing options of INGREZZA once-daily
provide sustained and clinically meaningful reductions in tardive
dyskinesia symptoms and are well tolerated."
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.
"Approximately 90% of patients treated with INGREZZA in the
long-term KINECT 4 study reported that their involuntary movements
were reduced by 50% or more, further demonstrating that treatment
with INGREZZA can provide patients with much-needed relief from the
debilitating symptoms of tardive dyskinesia that can also impact
their social, emotional and physical well-being," said Eiry W.
Roberts, M.D., Chief Medical Officer of Neurocrine Biosciences. "As
we continue to understand the full impact that the involuntary
movements of tardive dyskinesia can have on a patient, it is
important that healthcare providers have an effective and
well-tolerated treatment option like INGREZZA to help patients
manage this burdensome and isolating movement disorder."
Of the 163 patients included for analysis, 107 (65.6%) were
escalated to the 80 mg/day dose at the week 4 escalation visit.
Based on clinician judgment, 45 (27.6%) were maintained on the 40
mg/day dose for tolerability reasons or because they were already
experiencing an adequate treatment response. In the group of
patients that required a dose reduction from 80 to 40 mg/day
(n=11), efficacy did not appear to be compromised in this small
subgroup of patients.
The most common treatment-emergent adverse events (TEAE)
reported in ≥5% of all INGREZZA treated patients after week 4 were
urinary tract infection (8.5%) and headache (5.2%).
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.
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
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, chorea in
Huntington 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 from INGREZZA and the continued success
of the launch of 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 and uncertainties
relating to factors that may limit demand for 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 September 30, 2019.
Neurocrine disclaims any obligation to update the statements
contained in this press release after the date hereof.
References:
- Marder, S. et al. A Phase 3, 1-Year, Open-Label Trial of
Valbenazine in Adults With Tardive Dyskinesia. J. Clin.
Psychopharmacol., 39 (2019), pp 620-627. doi:
10.1097/JCP.0000000000001111
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